{"id":27283,"date":"2021-07-22T12:00:00","date_gmt":"2021-07-22T12:00:00","guid":{"rendered":"https:\/\/www.cancer.gov\/news-events\/cancer-currents-blog\/2021\/red-meat-colorectal-cancer-genetic-signature"},"modified":"2024-11-03T15:14:34","modified_gmt":"2024-11-03T15:14:34","slug":"pattern-of-dna-damage-links-colorectal-cancer-and-diet-high-in-red-meat","status":"publish","type":"post","link":"https:\/\/ogkologos.com\/en\/pattern-of-dna-damage-links-colorectal-cancer-and-diet-high-in-red-meat\/","title":{"rendered":"Pattern of DNA Damage Links Colorectal Cancer and Diet High in Red Meat"},"content":{"rendered":"

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Researchers have identified a consistent pattern of DNA damage in the colorectal tumors of people with frequent consumption of red and processed meat.<\/p>\n

Credit: iStock<\/p>\n<\/div>\n<\/figcaption><\/figure>\n<\/div>\n

Numerous studies have linked a diet high in red and processed meats with colorectal cancer, but it\u2019s been unclear how eating cheeseburgers, hot dogs, and lamb chops could fuel the development of this disease. <\/p>\n

New insights may soon be at hand. A team of researchers has identified a consistent pattern of DNA damage in the colorectal tumors<\/a> of people with frequent consumption of red and processed meat.<\/p>\n

These DNA<\/a> damage patterns, which researchers call \u201cmutational signatures,\u201d are akin to crime scene fingerprints left behind by a criminal. Researchers can study these patterns to trace the origins of the mutations<\/a> that led to a tumor\u2019s formation.<\/p>\n

The discovery of an alkylating mutational signature associated with the consumption of red and processed meats \u201cfurther implicates\u201d diet in the development of colorectal cancer, said Marios Giannakis, M.D., Ph.D., of the Dana-Farber Cancer Institute and Harvard Medical School, who co-led the study, published June 17 in Cancer Discovery<\/em>.<\/p>\n

To arrive at their findings, Dr. Giannakis and his colleagues analyzed tumor DNA from hundreds of people with colorectal cancer who had provided in-depth information about what they ate in the years before they were diagnosed with the disease. <\/p>\n

Understanding how red and processed meat may cause genetic damage that can lead to colorectal cancer may make it possible to prevent colorectal cancer, detect it early, and treat it with targeted therapies, Dr. Giannakis noted. One possible approach to prevention, for example, might be to identify people predisposed to accumulating alkylating damage and to encourage them to limit their intake of red meat, he said. <\/p>\n

\u201cThis is a really smart study,\u201d said Kurt Straif, M.D., Ph.D., who led the monographs program at the International Agency for Research on Cancer (IARC) that evaluated the carcinogenicity of meat consumption in 2015. The findings \u201cshed further light\u201d on the link between red and processed meat and colorectal cancer, continued Dr. Straif, who was not involved in the study.<\/p>\n

\u201cIt\u2019s making the evidence even stronger.\u201d <\/p>\n

Evidence Mounts<\/h2>\n

Evidence implicating red and processed meat in the development of colorectal cancer has been building for years. In 2015, based on data from 800 studies, IARC classified processed meat as a human carcinogen<\/a> (Group 1), meaning that there is enough evidence to conclude that it can cause cancer in humans. The evidence for red meat was less definitive, so IARC classified it as a probable carcinogen (Group 2A).<\/p>\n

Researchers are still trying to tease out exactly how red and processed meat might cause cancer. Some studies have suggested that preservatives such as nitrates and nitrites that are added to processed meats can produce compounds<\/a> that damage DNA. Other studies have looked into how chemicals that are formed when red meat is cooked at high temperatures, such as in grilling, cause the accumulation of mutations that lead to cancer. <\/p>\n

Using DNA analysis to identify mutational signatures can help scientists identify the origin of the DNA damage that initiated the growth of a given tumor. Mutational signatures are distinct patterns of DNA damage that reflect different mutational processes. Some mutational signatures arise from processes that happen within the body, such as DNA repair or oxidative stress<\/a>, whereas others are indicative of environmental exposures, such as UV light or tobacco smoke. <\/p>\n

Alkylating signatures are a type of mutational signature that arise when genetic material is damaged by chemicals that form lesions<\/a> in DNA, a process known as alkylation. When lesions formed by alkylation are not repaired properly, a specific pattern of mutational damage can result. <\/p>\n

Analysis of mutational signatures is increasingly being used to understand associations from epidemiologic studies. For example, scientists have identified specific mutational signatures associated with tobacco smoke exposure. <\/p>\n

\u201cFor lung cancer, we developed that mechanistic understanding maybe 10 or 20 years ago,\u201d said Paul Spellman, Ph.D., professor of molecular and medical genetics at Oregon Health & Science University, who studies the genomic origins of cancer but was not involved in the new study. \u201cWe now are getting there for red meat and processed meat and colorectal cancer.\u201d <\/p>\n

Looking for Genomic Clues<\/h2>\n

In this new study, Dr. Giannakis and his colleagues conducted whole-exome sequencing on samples of normal and tumor tissue from 900 people who were diagnosed with colorectal cancer while participating in one of three large, long-running epidemiologic studies: the Nurses\u2019 Health Studies I and II and the Health Professionals Follow-up Study. As part of the studies, participants provided in-depth information on their diet and general lifestyle.<\/p>\n

The researchers identified several mutational signatures in the tumor tissue, including an alkylating signature that was associated with red meat consumption. People in the top 10% of red meat consumption\u2014that is, those who consumed on average more than 150 grams, or roughly two servings, of processed or unprocessed red meat per day\u2014had the highest levels of the alkylating signature. <\/p>\n

This alkylating signature wasn\u2019t associated with diets high in chicken or fish. It also wasn\u2019t associated with other lifestyle factors such as smoking, high body mass index<\/a>, or high alcohol consumption.<\/p>\n

What\u2019s more, normal and cancerous tissue in the final length of the colon, known as the distal colon<\/a>, had much more alkylating DNA damage than tissue in other parts of the colon. Most colorectal cancers develop in the distal colon.<\/p>\n

The researchers also found that people whose tumors had the highest levels of the alkylating signature\u2014those in the top quarter of the group\u2014were more likely to die from colorectal cancer than people whose tumors had lower levels of the signature.<\/p>\n

The alkylating signatures were often seen alongside mutations in two genes strongly linked with cancer: KRAS<\/em> and PIK3CA<\/em>. Colorectal tumors with mutations in either of these genes had higher levels of the alkylating signature than tumors without these mutations, the researchers reported.<\/p>\n

\u201cA possible link could be that if you have high red meat consumption, you get this alkylating damage, and this alkylating damage [causes mutations in] the KRAS<\/em> genes. And we know that KRAS<\/em> mutations promote cancer growth,\u201d Dr. Giannakis said. \u201cIt doesn\u2019t mean that if you have this damage you will certainly get colorectal cancer. But it does raise the question: When does this damage get introduced? There could be opportunities to intervene early on.\u201d<\/p>\n

Toward Treatment and Prevention<\/h2>\n

Normal colorectal tissue also contained alkylating signatures, the researchers found. That could suggest that DNA damage begins long before the cancer starts to form, they wrote. One clue into the timing of when the DNA damage accumulates to a point of no return may lie in the MGMT<\/em> gene, which is involved in repair of DNA damage.<\/p>\n

Dr. Spellman explained that the alkylating signature was seen more frequently after the MGMT<\/em> gene was inactivated.<\/p>\n

\u201cThere may be environmental exposures or genetic predispositions that create an increased rate of such inactivation,\u201d he said. \u201cWhat it implies is that you’re probably fine until you get that MGMT<\/em> defect, and once you do, then red meat is really dangerous.”
  
Dr. Giannakis said more studies need to be done to better characterize these tumors. \u201cWe still need to do future studies to drill down the mechanism of action<\/a> even more,\u201d he said. \u201cFor example, can we prevent this alkylating damage from accumulating? Can we get a better sense of who\u2019s predisposed to getting this damage?\u201d<\/p>\n

The researchers are currently studying whether consumption of red meat is linked to the increasing incidence of colorectal cancer among young adults<\/a>.<\/p>\n

Nuri Faruk Aykan, M.D., of Istinye University in \u0130stanbul, said it would be important to expand these studies to different populations around the world, which may have different thresholds for when alkylating signatures arise. Dr. Aykan also wondered about the role of other factors, such as the colon\u2019s bacterial composition, or microbiome<\/a>, and specific types of red meat on the emergence of this alkylating signature.<\/p>\n

Dr. Giannakis agreed. \u201cI think we\u2019re just scratching the surface of figuring out the exact characteristics and epidemiology<\/a> of this, but now that we know how to find this alkylating signature, those future studies are certainly worth pursuing.\u201d<\/p>\n

Robert Turesky, Ph.D., of the University of Minnesota Masonic Cancer Center, who studies cancer causation, said it\u2019s also important to identify the specific chemical or chemicals in red and processed meat that are causing the mutations that lead to colorectal cancer.<\/p>\n

\u201cUltimately, if we can identify what some of these precursors are, there may be ways to mitigate their formation during cooking or processing of meats,\u201d Dr. Turesky said.<\/p>\n

Additional research could lead to changes in how groups like IARC classify red meat, Dr. Straif said. In fact, there have been examples in the past where IARC changed its classification on a particular cancer-causing risk factor<\/a> based on new mechanistic evidence, he noted.<\/p>\n

In the meantime, Dr. Giannakis said, having a balanced diet is key to a healthy lifestyle.<\/p>\n

Source<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

July 22, 2021, by NCI Staff Researchers have identified a consistent pattern of DNA damage in the colorectal tumors of people with frequent consumption of red and processed meat. Credit: iStock Numerous studies have linked a diet high in red and processed meats with colorectal cancer, but it\u2019s been unclear how eating cheeseburgers, hot dogs, […]<\/p>\n","protected":false},"author":2,"featured_media":27284,"comment_status":"closed","ping_status":"closed","sticky":false,"template":"","format":"standard","meta":{"_monsterinsights_skip_tracking":false,"footnotes":""},"categories":[5137],"tags":[],"class_list":["post-27283","post","type-post","status-publish","format-standard","has-post-thumbnail","hentry","category-world-news"],"_links":{"self":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/27283","targetHints":{"allow":["GET"]}}],"collection":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts"}],"about":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/types\/post"}],"author":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/users\/2"}],"replies":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/comments?post=27283"}],"version-history":[{"count":1,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/27283\/revisions"}],"predecessor-version":[{"id":43693,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/posts\/27283\/revisions\/43693"}],"wp:featuredmedia":[{"embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media\/27284"}],"wp:attachment":[{"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/media?parent=27283"}],"wp:term":[{"taxonomy":"category","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/categories?post=27283"},{"taxonomy":"post_tag","embeddable":true,"href":"https:\/\/ogkologos.com\/en\/wp-json\/wp\/v2\/tags?post=27283"}],"curies":[{"name":"wp","href":"https:\/\/api.w.org\/{rel}","templated":true}]}}