268 | id == 268
268 | category_id == 9
268 | category_order == 6
268 | category_name == Longevity
268 | category_color == #C47AC0
268 | slug == COMT-cancer
268 | title == Can This Gene Influence Your Risk of Cancer (COMT)?
268 | meta_description == The COMT gene breaks down estrogens and is associated with cancer prevention. Learn more here!
268 | summary == <p style="text-align:justify"><strong>The COMT gene encodes a protein that breaks down not only catecholamine neurotransmitters, but also estrogens and their byproducts. Variants with low activity have been associated with increased rates of some cancer types. Read on to learn where your COMT gene stands!</strong><br />  &nbsp;</p>
268 | overall_score_text == Your Cancer Score (based on COMT Gene)
268 | image == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/background/COMT--Cancer.jpg
268 | author_id == 12
268 | author_name == Carlos Tello
268 | author_title == PhD
268 | author_order == 55
268 | author_photo == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/author-photo/CarlosTello.webp
268 | author_intro == <p><strong>Carlos received his PhD and MS from the Universidad de Sevilla.</strong></p>    <p>Carlos spent 9 years in the laboratory investigating mineral transport in plants. He then started working as a freelancer, mainly in science writing, editing, and consulting. Carlos is passionate about learning the mechanisms behind biological processes and communicating science to both academic and non-academic audiences. He strongly believes that scientific literacy is crucial to maintain a healthy lifestyle and avoid falling for scams.</p>
268 | author_social_media_name == linkedin
268 | author_social_media_icon == https://sd-selfdecode-assets-prod.s3.amazonaws.com/blog/social-icon/linkedin.png
268 | author_social_order == 1
268 | author_social_link == https://www.linkedin.com/in/carlos-tello-lacal-b946b4a7/
268 | reviewer_id == 14
268 | reviewer_name == Shany Lahan
268 | reviewer_title == MS (Neuroscience)
268 | medical_reviewer_id == 11
268 | medical_reviewer_name == Puya Yazdi
268 | medical_reviewer_title == MD
268 | publish_date == 2020
268 | publish_date == 8
268 | publish_date == 12
268 | avg_rating == 5.0
268 | tags_id == 164
268 | tags_name == Cancer
268 | tags_id == 505
268 | tags_name == Catecholamines
268 | tags_id == 65
268 | tags_name == COMT Gene
268 | tags_id == 133
268 | tags_name == Estrogen
268 | permissions_favorite == False
268 | permissions_rate == False
268 | content_article == <p><em><span style="font-weight: 400;">The information in this post is presented for educational purposes only, and should not be used to replace standard medical care. If you suspect that you have cancer, you should immediately report to a physician.</span></em></p> <h2><strong>What Is the <em>COMT </em>Gene?</strong></h2> <p><span style="font-weight: 400;">The </span><a href="../../../gene/comt/"><em><span style="font-weight: 400;">COMT</span></em></a> <span style="font-weight: 400;">gene codes for an enzyme called </span><em><span style="font-weight: 400;">catechol-o-methyltransferase</span></em><span style="font-weight: 400;"> (also called COMT). As its name implies, COMT transfers a methyl group to catechol-containing compounds. COMT uses </span><a href="https://selfhacked.com/blog/s-adenosyl-l-methionine/"><span style="font-weight: 400;">SAM-e</span></a><span style="font-weight: 400;"> as its methyl donor. Therefore, having either too little SAM-e, or too much S-adenosylhomocysteine (SAH) &mdash; which is formed when SAM-e loses its methyl group &mdash; results in inhibition of COMT [</span><a href="https://pubmed.ncbi.nlm.nih.gov/8576124/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/12371153/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The main function of COMT is to help break down </span><em><span style="font-weight: 400;">catecholamines</span></em><span style="font-weight: 400;">, a family of neurotransmitters that includes </span><a href="https://selfhacked.com/blog/dopamine/"><span style="font-weight: 400;">dopamine</span></a><span style="font-weight: 400;">, </span><a href="https://selfhacked.com/blog/norepinephrine-stress-hormone/"><span style="font-weight: 400;">norepinephrine</span></a><span style="font-weight: 400;"> (also known as </span><a href="https://selfhacked.com/blog/norepinephrine-stress-hormone/"><span style="font-weight: 400;">noradrenaline</span></a><span style="font-weight: 400;">), and epinephrine (also known as adrenaline) [</span><a href="https://pubmed.ncbi.nlm.nih.gov/16878403/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In addition, COMT helps break down other compounds such as </span><a href="https://selfhacked.com/blog/estradiol/"><span style="font-weight: 400;">estrogen</span></a><span style="font-weight: 400;"> byproducts, bioflavonoids (e.g., </span><a href="https://www.selfhacked.com/blog/quercetin-22-scientifically-proven-benefits-quercetin/"><span style="font-weight: 400;">quercetin</span></a><span style="font-weight: 400;"> and </span><a href="http://selfhacked.com/blog/15-science-based-health-benefits-fisetin-1-favorite/"><span style="font-weight: 400;">fisetin</span></a><span style="font-weight: 400;">), tea catechins, and certain drugs (e.g., </span><a href="https://www.selfhacked.com/blog/l-dopa-levodopa/"><span style="font-weight: 400;">L-DOPA</span></a><span style="font-weight: 400;">, and dobutamine) [</span><a href="https://pubmed.ncbi.nlm.nih.gov/11160877/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/17880176/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">COMT is widely distributed in organs such as the brain, adrenal glands, liver, kidneys, lungs, intestines, and mammary glands [</span><a href="https://pubmed.ncbi.nlm.nih.gov/8027527/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/8055944/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">The COMT gene encodes an enzyme of the nervous system that breaks down neurotransmitters, estrogen byproducts, and other catechol-containing chemicals by transferring a methyl group to them, from SAM-e.</span></p> <h3><strong>Estrogens and Cancer Risk</strong></h3> <p><span style="font-weight: 400;">Sustained exposure to estrogens increases the risk of certain cancer types. In tissues such as those of the breast, ovaries, and endometrium, these hormones promote cell growth and division. If a tumor expresses estrogen receptors (and is thus called an &lsquo;estrogen-responsive tumor&rsquo;), activation of these receptors by estrogens will promote its growth [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339663/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Alternatively, the breakdown of estrogens produces first catechols and finally quinones, which cause </span><a href="https://selfhacked.com/blog/oxidative-stress-101/"><span style="font-weight: 400;">oxidative stress</span></a><span style="font-weight: 400;"> and DNA damage that may turn cells cancerous &mdash; whether they belong to tissues that respond to estrogens or not [</span><a href="https://pubmed.ncbi.nlm.nih.gov/18566989/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4339663/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="font-weight: 400;">Cell-based studies show that COMT prevents the formation of quinones from estrogen, thus helping reduce cancer risk, by breaking down catechols into a compound with anticancer activity (2-methoxyestradiol) [</span><a href="https://pubmed.ncbi.nlm.nih.gov/11606384/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2096412/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/9240348/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/30904591/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Another enzyme, </span><a href="https://www.selfdecode.com/gene/CYP1b1/?utm_source=seo&amp;#38;utm_medium=selfhacked&amp;#38;utm_campaign=id00002"><span style="font-weight: 400;">CYP1</span></a><a href="https://www.selfhacked.com/blog/thiamine/"><span style="font-weight: 400;">B1</span></a><span style="font-weight: 400;">, transforms estrogens through an alternative pathway that produces the cancer-causing compound 4-methoxyestradiol. The breakdown of this compound by COMT is another anticancer mechanism of this protein [</span><a href="https://pubmed.ncbi.nlm.nih.gov/17507616/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152751/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Importantly, estrogens reduce </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">expression and activity. This may explain why the levels of COMT are lower in women, and may also explain the differing effects of COMT in men and women [</span><a href="https://pubmed.ncbi.nlm.nih.gov/10385681/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/30684530/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182110/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/21769726/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Estrogens stimulate the growth of some cancer types and their transformation produces cancer-causing compounds. COMT breaks down these hormones into compounds with anticancer activity.</span></p> <h2><strong>Your COMT Results for Cancer</strong></h2> <p>*4462461244087357*</p> <p>&nbsp;</p> <h3><strong>SNP Summary and Table</strong></h3> <p><strong>Primary SNP: </strong><strong><em>COMT </em></strong><strong>rs4680</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Normal cancer risk</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Increased risk of breast, lung, and esophageal cancers, especially in Asians</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">41% of the world population has genotype &lsquo;GG&rsquo;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">In people with European ancestry, both alleles are equally frequent</span></li> </ul> <p><strong>Other Important SNPs&nbsp;</strong></p> <p><strong><em>COMT </em></strong><strong>rs4633</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Normal cancer risk</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Increased risk of endometrial and lung cancer</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The genotype distribution is very similar to that of rs4680 for all ethnicities</span></li> </ul> <p><strong><em>COMT </em></strong><strong>rs737865</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Normal cancer risk</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Reduced risk of breast and lymph system cancer&nbsp;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">60% of the world population has genotype &lsquo;AA&rsquo;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;G&rsquo; variant is slightly more common in European descendents</span></li> </ul> <p><strong><em>COMT </em></strong><strong>rs165599&nbsp;</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;G&rsquo; = Normal cancer risk</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;A&rsquo; = Increased risk of colorectal cancer</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;G&rsquo; allele is slightly more frequent than &lsquo;A&rsquo; in the global population</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">In European descendants, &lsquo;A&rsquo; is the most common allele</span></li> </ul> <p><strong><em>COMT </em></strong><strong>rs2020917&nbsp;</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Normal cancer risk</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Reduced risk of breast cancer</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The genotype distribution is very similar to that of rs737865 for all ethnicities</span></li> </ul> <p><strong><em>COMT </em></strong><strong>rs9332377&nbsp;</strong></p> <ul> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;C&rsquo; = Normal cancer risk</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">&lsquo;T&rsquo; = Increased risk of stomach cancer</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">Worldwide, 70% of the population has &lsquo;CC&rsquo;</span></li> <li style="font-weight: 400;"><span style="font-weight: 400;">The &lsquo;T&rsquo; variant is even less common in people of European ancestry</span></li> </ul> <p>&nbsp;</p> <p>*5136549428246977*</p> <p>&nbsp;</p> <h2><strong>Influence of <em>COMT </em>Variants on Cancer Risk</strong></h2> <h3><strong>Rs4680</strong></h3> <p><span style="font-weight: 400;">By far, </span><a href="../../../snp/rs4680/"><span style="font-weight: 400;">rs4680</span></a><span style="font-weight: 400;"> is the most widely-studied COMT gene variant. Its minor &lsquo;A&rsquo; allele encodes a less-stable protein that results in reduced COMT levels and activity [</span><a href="https://pubmed.ncbi.nlm.nih.gov/7703232/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/10581325/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">This variant has been associated with increased rates of some cancer types, but mainly in Asian populations [</span><a href="https://pubmed.ncbi.nlm.nih.gov/24307619/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599643/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">For instance, the &lsquo;A&rsquo; variant is associated with breast cancer in Chinese, Japanese, Indian, and other Asian populations. Surprisingly, this variant was slightly </span><em><span style="font-weight: 400;">protective </span></em><span style="font-weight: 400;">in Caucasian women. These discrepancies may be due to genetic differences among ethnicities. In line with this, a study on Slovenian women found this variant only associated with breast cancer when combined with a risk allele of </span><em><span style="font-weight: 400;">CYP1B1 </span></em><span style="font-weight: 400;">[</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4599643/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4090317/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555530/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/22297695/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/20130981/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152751/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">This allele also increases the risk of lung cancer, especially among Chinese non-smoking women [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4196007/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/22331461/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106617/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4694264/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Two Chinese studies linked this variant with an increased risk of esophageal cancer [</span><a href="https://pubmed.ncbi.nlm.nih.gov/24307619/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/20979431/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/18324659/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">A widely-investigated <em>COMT </em>underactive variant is associated with increased rates of some cancers, especially in Asian populations.</span></p> <h3><strong>Other Variants</strong></h3> <p><span style="font-weight: 400;">The minor &lsquo;T&rsquo; allele of </span><a href="../../../snp/rs4633/"><span style="font-weight: 400;">rs4633</span></a><span style="font-weight: 400;"> increases </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">expression but may alter the activity of the protein. This variant has been associated with higher rates of endometrial cancer in American women and lung cancer in Chinese women [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6115408/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3152328/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/18324659/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106617/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The minor &lsquo;G&rsquo; variant of </span><a href="../../../snp/rs737865/"><span style="font-weight: 400;">rs737865</span></a><span style="font-weight: 400;"> has been associated with a reduced risk of breast and lymph system (non-Hodgkin lymphoma) cancer in American studies. Although this suggests increased COMT activity, studies failed to link this polymorphism with changes in COMT expression, protein levels, and enzyme activity [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518124/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/16214922/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/30218069/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1182110/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The minor &lsquo;A&rsquo; allele of </span><a href="../../../snp/rs165599/"><span style="font-weight: 400;">rs165599</span></a><span style="font-weight: 400;"> reduces </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">expression. This variant was associated with higher colorectal cancer rates in a Chinese study [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1180576/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/32059146/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The minor &lsquo;T&rsquo; allele of </span><a href="../../../snp/rs2020917/"><span style="font-weight: 400;">rs2020917</span></a><span style="font-weight: 400;"> increases </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">expression and, possibly, activity. In line with this, this variant was associated with a reduced incidence of breast cancer in an American study [</span><a href="https://pubmed.ncbi.nlm.nih.gov/23351565/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2518124/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Finally, the minor &lsquo;T&rsquo; allele of </span><a href="../../../snp/rs9332377/"><span style="font-weight: 400;">rs9332377</span></a><span style="font-weight: 400;"> was weakly associated with an increased risk of stomach cancer in a Polish population [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2639034/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Several <em>COMT </em>variants may increase or reduce the risk of breast, endometrial, lung, lymph system, stomach, and colorectal cancer.</span></p> <h2><strong>Recommendations to Reduce Cancer Risk</strong></h2> <p><em><span style="font-weight: 400;">You may try the complementary approaches listed below if you and your doctor determine that they could be appropriate for you. Discuss the strategies listed here with your doctor. Remember that none of them should ever be done in place of what your doctor recommends or prescribes.</span></em></p> <p>*8033989898725997*</p> <p>&nbsp;</p> <h3><strong>Diet</strong></h3> <h4><strong>Green Tea (Epigallocatechin Gallate)</strong></h4> <p><a href="https://selfhacked.com/blog/green-tea/"><span style="font-weight: 400;">Green tea</span></a><span style="font-weight: 400;"> is rich in catechol-containing flavanols such as </span><a href="https://www.selfhacked.com/blog/green-tea/"><span style="font-weight: 400;">epigallocatechin</span></a><span style="font-weight: 400;"> gallate (</span><a href="https://selfhacked.com/blog/green-tea/"><span style="font-weight: 400;">EGCG</span></a><span style="font-weight: 400;">), epicatechin, and catechin</span> <span style="font-weight: 400;">[</span><a href="https://pubmed.ncbi.nlm.nih.gov/10837321/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">High intake of green tea has been associated with a reduced incidence of several cancer types, such as breast, ovarian, prostate, mouth, esophageal, stomach, colorectal, liver, endometrial, lung, bladder, and lymph system cancers. However, most studies were done in Asian people. Additional studies in other populations will be needed to determine if these effects may be ethnicity-dependent [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6316745/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514950/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5380255/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/24389399/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/23368908/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/28980522/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5514915/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/26412579/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/26138307/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/19128856/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/23052791/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/31045454/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Its most abundant flavanol, EGCG, is quickly broken down by COMT and doesn&rsquo;t seem to impair COMT activity even at high doses. For this reason, its beneficial effects may be enhanced in carriers of underactive </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">variants [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3010377/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/24972245/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a study on Asian American women, only those who carried at least one copy of the &lsquo;A&rsquo; variant at rs4680 benefited from the anti-breast cancer effects of green tea. However, drinking green tea reduced the risk of breast cancer in 2 studies on Chinese and Japanese women regardless of their </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">genotypes [</span><a href="https://pubmed.ncbi.nlm.nih.gov/14612555/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2646205/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/24274352/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In contrast, the high-activity &lsquo;G&rsquo; variant of rs4680 reduced the ability of green tea to prevent lung cancer in a Taiwanese study [</span><a href="https://pubmed.ncbi.nlm.nih.gov/30157136/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In mice and cells, inhibiting COMT enhanced the availability and anticancer effects of EGCG [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4509505/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3304301/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">High intake of green tea has been associated with reduced incidence of multiple cancer types. Because its natural flavonoid <em>epigallocatechin gallate</em> is broken down by COMT, people with underactive variants may especially benefit from green tea.</span></p> <h4><strong>Plant Phytoestrogens (Soy, Flax, Red Clover)</strong></h4> <p><span style="font-weight: 400;">Phytoestrogens are plant-derived flavonoids that resemble the sex hormone estrogen. When consumed, phytoestrogens can bind to estrogen receptors and either mimic or block the effects of this hormone. Additionally, they build up in tissues and can be toxic to cancer cells.</span></p> <p><strong>Soy </strong><span style="font-weight: 400;">is rich in a class of phytoestrogens called isoflavones. Multiple studies have associated eating a diet rich in soy with a reduced incidence of breast, ovarian, prostate, endometrial, stomach (only non-fermented soy), colorectal, and lung cancer. However, most studies were done in Asian people, and studies including participants of other races have reported somewhat less-promising results [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3930722/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/25422183/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/27260185/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/27914914/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5571710/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4864327/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3252551/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The &lsquo;AA&rsquo; genotype of rs4680 increased the risk of breast cancer in Chinese postmenopausal women. However, eating high levels of soy isoflavones reduced its incidence to levels comparable to those of &lsquo;G&rsquo; carriers [</span><a href="https://pubmed.ncbi.nlm.nih.gov/20591221/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/21438753/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In prostate cancer cells, the combination of the soy isoflavone genistein with the glucosinolate </span><a href="https://selfhacked.com/blog/diindolylmethane-dim/"><span style="font-weight: 400;">diindolylmethane</span></a><span style="font-weight: 400;"> increased </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">expression and activity, suggesting it helps prevent estrogen-induced cancer [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3415863/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><strong>Flaxseed </strong><span style="font-weight: 400;">contains another type of phytoestrogen called </span><em><span style="font-weight: 400;">lignans</span></em><span style="font-weight: 400;">. Multiple studies have reported that dietary flaxseed can help prevent breast cancer &mdash; especially in postmenopausal women &mdash; as well as increase the survival of breast cancer patients [</span><a href="https://pubmed.ncbi.nlm.nih.gov/24013641/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5808339/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The minor variants of rs4680 (&lsquo;A&rsquo;) and rs4633 (&lsquo;T&rsquo;) have been associated with increased removal of estrogen byproducts in urine after consumption of flaxseed, suggesting higher benefits in terms of cancer prevention [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5613245/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6363829/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Certain plant foods like soy and flaxseed contain phytoestrogens, which resemble human estrogen. Some studies suggest that <em>COMT </em>variants may influence the anticancer effects of these compounds.</span></p> <h4><strong>Sufficient Folate Intake</strong></h4> <p><a href="https://selfhacked.com/blog/16-proven-benefits-vitamin-b9-folate-folic-acid/"><span style="font-weight: 400;">Folate</span></a><span style="font-weight: 400;"> (</span><a href="https://selfhacked.com/blog/16-proven-benefits-vitamin-b9-folate-folic-acid/"><span style="font-weight: 400;">vitamin B9</span></a><span style="font-weight: 400;">) is an antioxidant vitamin with key roles in cellular metabolism, blood cell production, immune response, brain development and function, and fertility [</span><a href="https://pubmed.ncbi.nlm.nih.gov/29889360/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/17209196/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/1887065/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/10746355/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4175124/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Importantly, folate helps prevent cancer by controlling gene expression through its role in DNA </span><a href="https://selfhacked.com/blog/what-is-methylation-and-how-does-it-affect-our-health/"><span style="font-weight: 400;">methylation</span></a><span style="font-weight: 400;">. This vitamin also restores SAM-e levels by producing its precursor methionine from the amino acid homocysteine. A folate-rich diet (but not above a normal dietary range) is associated with a reduced incidence of several cancer types such as colorectal, esophageal, stomach, pancreatic, lung, and breast cancer [</span><a href="https://pubmed.ncbi.nlm.nih.gov/16251634/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/17030196/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/10794479/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/11585746/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a study on American women, low blood folate levels were associated with increased breast cancer incidence only in those with two copies of the &lsquo;A&rsquo; variant at rs4680. The authors speculated that the increased SAH levels resulting from low folate would have larger inhibitory effects on this underactive </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">variant [</span><a href="https://pubmed.ncbi.nlm.nih.gov/11577006/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Food sources of this vitamin include green leafy vegetables, citrus fruits, and legumes [</span><a href="https://www.ncbi.nlm.nih.gov/books/NBK114318"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Folate is an antioxidant vitamin with key roles in cellular metabolism, immune response, brain function, and fertility. Underactive <em>COMT </em>variants can further increase cancer risk in people with folate deficiency.</span></p> <h4><strong>Dietary Flavonoids (Herbs, Spices, Fruits, and Vegetables)</strong></h4> <p><span style="font-weight: 400;">Flavonoids are phenolic compounds naturally found in plants. Owing to their antioxidant activity, these compounds have been widely investigated due to their potential role in preventing chronic conditions, such as heart disease and cancer. Food sources of these compounds include many herbs and spices, onions, apples, grapes, pomegranates, berries, green leafy vegetables, and red wine [</span><a href="https://www.ncbi.nlm.nih.gov/pubmed/31004736"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">A lot of them, including flavonols (</span><a href="https://www.selfhacked.com/blog/quercetin-22-scientifically-proven-benefits-quercetin/"><span style="font-weight: 400;">quercetin</span></a><span style="font-weight: 400;">, fisetin, and </span><a href="https://selfhacked.com/blog/top-15-scientific-health-benefits-of-resveratrol-with-references/"><span style="font-weight: 400;">resveratrol</span></a><span style="font-weight: 400;">) and flavones (</span><a href="http://selfhacked.com/blog/top-11-science-based-health-benefits-luteolin/"><span style="font-weight: 400;">luteolin</span></a><span style="font-weight: 400;">), are catechol-containing substances that can be broken down by COMT. Depending on the flavonoid, </span><a href="https://selfhacked.com/blog/what-is-methylation-and-how-does-it-affect-our-health/"><span style="font-weight: 400;">methylation</span></a><span style="font-weight: 400;"> by COMT can either reduce its effects or be required to convert it to an active compound [</span><a href="https://pubmed.ncbi.nlm.nih.gov/27826992/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Among flavonoid classes, flavonols are most effective at preventing breast, ovarian, mouth, throat, colorectal, lung, and prostate cancer, while flavones mainly reduce the risk of breast, colorectal, and kidney cancers [</span><a href="https://pubmed.ncbi.nlm.nih.gov/20924962/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/12198000/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Aside from this, plant catechols can act as COMT inhibitors that reduce the ability of this enzyme to break down neurotransmitters and estrogens. For instance, quercetin is a strong COMT inhibitor. This means quercetin may have detrimental effects when taken alone. However, it may reduce the breakdown of other flavonoids such as green tea polyphenols and resveratrol by COMT, thus enhancing their effects [</span><a href="https://pubmed.ncbi.nlm.nih.gov/15254334/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/27826992/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6371058/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/32468451/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3590855/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/22452782/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3858726/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/25669932/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a clinical trial in which healthy volunteers drank quercetin-rich blueberry and apple juice for 4 weeks, carriers of the &lsquo;A&rsquo; variant at rs4680 were observed to benefit less in terms of DNA damage reduction [</span><a href="https://pubmed.ncbi.nlm.nih.gov/17602170/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In animal studies, quercetin reduced the breakdown of estrogens by COMT and increased the risk of breast and kidney cancer [</span><a href="https://pubmed.ncbi.nlm.nih.gov/8576124/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4006967/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/8128490/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Plant flavonoids are potent dietary antioxidants that have been studied extensively for their potential to protect against cancer. Quercetin is a COMT inhibitor that may be recommended or best avoided depending on your <em>COMT </em>genotype and combination with other flavonoids.</span></p> <h3><strong>Lifestyle</strong></h3> <h4><strong>Maintaining a Healthy Weight</strong></h4> <p><span style="font-weight: 400;">In addition to many other health issues, excess weight is associated with an increased incidence of some cancer types, especially of the kidneys, colon (only in men), breast, endometrium, and ovaries (in women not using hormone replacement therapy) [</span><a href="https://pubmed.ncbi.nlm.nih.gov/25757865/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a study on Canadian women, the increased breast cancer risk due to high BMI was only observed in carriers of the &lsquo;G&rsquo; variant at rs4680 [</span><a href="https://pubmed.ncbi.nlm.nih.gov/21129090/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In addition to a healthy diet low in saturated fats and refined carbohydrates, engagement in regular physical </span><a href="https://selfhacked.com/blog/top-14-proven-health-benefits-exercise-references-mechanisms/"><span style="font-weight: 400;">exercise</span></a><span style="font-weight: 400;"> is important in maintaining a healthy weight. Unfortunately, exercise may be less effective in carriers of the &lsquo;A&rsquo; variant at rs4680. In two clinical trials on overweight postmenopausal women, this allele reduced </span><a href="http://selfhacked.com/blog/a-comprehensive-list-of-effective-ways-to-lose-weight/"><span style="font-weight: 400;">weight loss</span></a><span style="font-weight: 400;"> and muscle gain from exercise [</span><a href="https://pubmed.ncbi.nlm.nih.gov/15229337/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/15229337/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Excess weight is associated with some cancer types. Certain <em>COMT </em>variants may influence not only the risk of cancer from excess weight, but also the effectiveness of exercise in regards to losing weight.</span></p> <h4><strong>Avoiding Cigarette Smoke</strong></h4> <p><span style="font-weight: 400;">In addition to its well-known role in causing lung cancer, both active- and second-hand exposure to cigarette smoke have been associated with several types of cancer, including breast, head and neck, upper digestive, prostate, colorectal, cervical, bladder, and kidney cancer [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6194454/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/27369767/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/26546245"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/21330928/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2836346/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/19088354/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/30407555/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/26149669/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">The &lsquo;A&rsquo; variant of rs4680 further increased the risk of lung cancer in a study on Japanese smokers [</span><a href="https://pubmed.ncbi.nlm.nih.gov/27644662/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In the case of breast cancer, the &lsquo;G&rsquo; allele has been associated with an increased risk of breast cancer linked to smoking. An increased breakdown of the anticancer compound 2-methoxyestradiol was proposed as the most likely mechanism [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1373621/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Possibly because it encodes a COMT form that breaks down </span><a href="https://selfhacked.com/blog/28-proven-health-benefits-nicotine-4-potential-risks/"><span style="font-weight: 400;">nicotine</span></a><span style="font-weight: 400;"> more slowly, the &lsquo;A&rsquo; variant at this polymorphism is associated with increased dependence [</span><a href="https://pubmed.ncbi.nlm.nih.gov/16395295/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/17206495/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3028189/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5418756/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">However, carriers of the &lsquo;G&rsquo; variant experience worse cognitive symptoms during abstinence and break down nicotine replacement faster. This may explain why carrying the &lsquo;A&rsquo; variant is associated with better success of nicotine replacement therapies [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2873693/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3896978/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2031911/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/26555332/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Bupropion is an antidepressant often prescribed as an aid to smoking cessation that increases dopamine levels by inhibiting its removal. In a clinical trial, carrying the &lsquo;A&rsquo; variant at </span><a href="../../../snp/rs165599/"><span style="font-weight: 400;">rs165599</span></a><span style="font-weight: 400;"> was associated with increased success of this therapy in African Americans, while &lsquo;G&rsquo; combined with the &lsquo;G&rsquo; allele of rs737865 predicted failure in European Americans [</span><a href="https://pubmed.ncbi.nlm.nih.gov/16876132/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Exposure to cigarette smoke has been associated with increased rates and worse outcomes of cancer. Different <em>COMT </em>variants can influence the risk of smoking-associated cancers and the success rate of smoking cessation therapies.</span></p> <h4><strong>Reducing Exposure to Toxic Chemicals</strong></h4> <p><span style="font-weight: 400;">Exposure to different chemicals, such as polycyclic aromatic hydrocarbons (PAH) and fuel combustion byproducts, has been consistently associated with different cancer types. These chemicals cause DNA damage that may trigger tumor development [</span><a href="https://pubmed.ncbi.nlm.nih.gov/20430714/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/26735351/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/24935254/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2903550/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/20584305/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6929467/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/29025048/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">PAHs are found in fuels such as coal and gasoline. We are exposed to them when we breathe air contaminated with vehicle exhaust, cigarette smoke, wood smoke and fumes from asphalt roads, and when we eat charred or grilled foods.</span></p> <p><span style="font-weight: 400;">COMT effectively broke down PAH in test tubes. This suggests that carrying underactive </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">variants may pose disadvantages in terms of their </span><a href="https://selfhacked.com/blog/the-science-of-detoxification/"><span style="font-weight: 400;">detoxification</span></a><span style="font-weight: 400;"> ability [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3138279/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In line with this, both the &lsquo;T&rsquo; variant of rs4633 and the &lsquo;A&rsquo; variant of rs4680 further increased the risk of lung cancer from occupational exposure to cooking fumes, soot, and other toxic chemicals in Chinese non-smoking women [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6106617/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">Perfluorinated compounds are extremely stable chemicals mainly used in the production of teflon, water-proof and stain-resistant fabrics, and fire-fighting foam. Due to their widespread presence, persistence, and toxic effects in animals, they are recognized as environmental contaminants.&nbsp;</span></p> <p><span style="font-weight: 400;">Human research is sparse, but&nbsp; these compounds have been associated with some cancer types such as leukemia, prostate, kidney, bladder, breast, and testicular cancer [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6172956/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In women exposed to high levels of perfluorinated compounds, carrying at least one copy of the &lsquo;A&rsquo; variant at rs4680 further increased the risk of breast cancer [</span><a href="https://pubmed.ncbi.nlm.nih.gov/28157646/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4234380/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Many toxic chemicals may cause DNA damage. People exposed to pollutants are at greater risk of DNA damage, especially if they carry certain <em>COMT </em>variants.</span></p> <h4><strong>Reducing Alcohol Intake</strong></h4> <p><span style="font-weight: 400;">Consumption of alcohol is a well-known risk factor for several cancer types. Even at low or moderate doses, it increases the risk of mouth, throat, esophageal, breast, and colorectal cancer. Higher levels of consumption may further increase the risk of these cancers, and have also been associated with stomach, liver, gallbladder, pancreatic, and lung cancer. This risk may be amplified in people who also smoke [</span><a href="https://pubmed.ncbi.nlm.nih.gov/22910838/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5912140/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/26400678/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4453639/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a Japanese study, carrying the &lsquo;A&rsquo; variant of rs4680 further increased the risk of lung cancer in heavy drinkers [</span><a href="https://pubmed.ncbi.nlm.nih.gov/27644662/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Alcohol intake is a well-known risk factor for several cancer types. An underactive <em>COMT </em>variant has been associated with lung cancer in heavy drinkers.</span></p> <h4><strong>Discussing Hormone Therapies with a Doctor</strong></h4> <p><span style="font-weight: 400;">Postmenopausal women often experience symptoms such as hot flashes and vaginal discomfort because their ovaries stop producing estrogen. </span><strong>Hormone replacement therapy</strong><span style="font-weight: 400;"> (</span><strong>HRT</strong><span style="font-weight: 400;">) with estrogen, usually combined with </span><a href="http://selfhacked.com/blog/top-21-science-based-health-benefits-progesterone-4-drawbacks/"><span style="font-weight: 400;">progesterone</span></a><span style="font-weight: 400;"> to help prevent endometrial cancer, is often prescribed to manage these symptoms.</span></p> <p><span style="font-weight: 400;">HRT has been associated with a slightly higher risk of breast and ovarian cancers, especially if combining estrogen and progesterone. However, the results are inconsistent and most doctors agree that the benefits often outweigh the risks [</span><a href="https://pubmed.ncbi.nlm.nih.gov/12117397/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4881107/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6386596/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pubmed/30570740"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/31542834/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/28783542/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a study on Danish women, the incidence of breast cancer among HRT users was lower for those with the &lsquo;AA&rsquo; genotype at rs4680 when compared to carriers of the &lsquo;G&rsquo; variant. However, the &lsquo;A&rsquo; variant increased the risk of breast cancer in women using HRT that also carried certain variants of the gene encoding the detoxifying enzyme </span><a href="http://selfhacked.com/blog/30-scientifically-proven-health-benefits-glutathione/"><span style="font-weight: 400;">glutathione</span></a><span style="font-weight: 400;">-S-transferase (</span><em><span style="font-weight: 400;">GST</span></em><span style="font-weight: 400;">)</span> <span style="font-weight: 400;">[</span><a href="https://pubmed.ncbi.nlm.nih.gov/23869875/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/11773866/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><strong>Hormone-based birth control methods</strong><span style="font-weight: 400;"> such as oral contraceptives, birth control shots, patches, and implants (IUDs and rings) have also been associated with an increased risk of breast cancer. Conversely, they may help prevent ovarian cancer, possibly because they suppress ovulation [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6547482/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6738995/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/24145348/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a Canadian study, an increased breast cancer risk from oral contraceptives was only observed in carriers of the major &rsquo;G&rsquo; allele at rs4680. The authors suggested that the high exposure to estrogens from contraceptives increases the production of the anticancer 2-methoxyestradiol over cancer-causing byproducts. By reducing the breakdown of 2-methoxyestradiol, the &lsquo;A&rsquo; variant would be protective in this case [</span><a href="https://pubmed.ncbi.nlm.nih.gov/21129090/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><strong>Tamoxifen </strong><span style="font-weight: 400;">is a drug that binds to estrogen receptors and blocks their effects in the breasts. For this reason, tamoxifen is used for both the treatment and prevention of estrogen receptor-positive breast tumors.</span></p> <p><span style="font-weight: 400;">In female rats, treatment with tamoxifen increased </span><em><span style="font-weight: 400;">COMT </span></em><span style="font-weight: 400;">expression and activity, especially in the prefrontal cortex and kidneys [</span><a href="https://pubmed.ncbi.nlm.nih.gov/22100850/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Breast and ovarian cancers are often highly sensitive to estrogen and other hormones. Your <em>COMT </em>genotype may determine whether you should use HRT, birth control, or other hormone-based therapies.</span></p> <h3><strong>Supplements</strong></h3> <h4><strong>Vitamin E</strong></h4> <p><a href="https://selfhacked.com/blog/vitamin-e-can-help-fertility-pregnancy/"><span style="font-weight: 400;">Vitamin E</span></a><span style="font-weight: 400;"> is a fat-soluble, antioxidant vitamin essential to maintaining brain, heart, skin, and immune system health, as well as maintaining fertility. Deficiency in this vitamin has been associated with increased incidence of several cancer types, heart disease, and dementia [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6250988/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/30630552/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/24144963/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In a large-scale study on American women, vitamin E supplementation reduced cancer incidence in women with two copies of the &lsquo;A&rsquo; allele at rs4680 and &lsquo;C&rsquo; at rs4818, but increased it in those carrying only the major variants of these polymorphisms [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6624170/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In addition to supplementing, you can obtain vitamin E from food sources such as nuts, cereal grains, and plant oils [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2956867/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].&nbsp;</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">Vitamin E is an antioxidant vitamin essential to maintain brain, heart, skin, and immune health. Supplementation with vitamin E may be beneficial or detrimental in cancer prevention depending on your <em>COMT </em>variant.</span></p> <h4><strong>SAM-e</strong></h4> <p><a href="https://selfhacked.com/blog/s-adenosyl-l-methionine/"><span style="font-weight: 400;">SAM-e</span></a><span style="font-weight: 400;">, the primary &ldquo;methyl donor&rdquo; used to activate the COMT enzyme, is classified as a supplement in the US and a prescription drug in some European countries.</span></p> <p><span style="font-weight: 400;">By supporting methylation, SAM-e may prevent the uncontrolled division of cancer cells and inhibit cancer-promoting enzymes [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2408691/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="font-weight: 400;">In mice studies, scientists observed inhibitory effects of SAM-e on breast, liver, stomach, and bone cancer [</span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5797041/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4430266/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://pubmed.ncbi.nlm.nih.gov/20663323/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">, </span><a href="https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5739599/"><span style="font-weight: 400;">R</span></a><span style="font-weight: 400;">].</span></p> <p><span style="background-color: #e8ebfc; border-left: 2px solid #4569fa; display: block; padding: 20px;">SAM-e is the methyl donor required for COMT activity. Preliminary research suggests its potential in cancer prevention.</span></p>
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268 | content_learn_more_4462461244087357_text == Based on the variants we looked at, your COMT gene is associated with somewhat increased cancer risk. Eating a diet rich in green tea, phytoestrogens, folate, and flavonoids, reducing your exposure to cigarette smoke, pollutants, and alcohol, and discussing hormone therapies with a doctor can help. Keep scrolling to find out more.
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rsIDs = rs165599,rs4633,rs737865,rs4818,rs9332377,rs2020917,rs4680
rsStatus = rs165599,ARVCF,chr22,19969258,G,A,C,,23,11,HET
rsStatus = rs4633,COMT,chr22,19962712,C,T,,,21,13,HET
rsStatus = rs737865,COMT,chr22,19942598,A,G,T,,17,12,HET
rsStatus = rs4818,COMT,chr22,19963684,C,G,T,,18,13,HET
rsStatus = rs9332377,ARVCF,chr22,19968169,C,A,T,,53,0,Normal
rsStatus = rs2020917,COMT,chr22,19941361,C,T,,,24,16,HET
rsStatus = rs4680,COMT,chr22,19963748,G,A,,,19,11,HET
