Kana Wu, M.D., Ph.D., Principal Research Scientist in the Department of Nutrition at Harvard T. H. Chan School of Public Health, Member of the Dana-Farber/Harvard Cancer Center (DF/HCC, program affiliation: Cancer Epidemiology and Gastrointestinal Malignancies), Member of the Working Group for the IARC Monographs on the Evaluation of Carcinogenic Risks to Humans Volume 114 (Red Meat and Processed Meat) Speaks about the Pattern of DNA Damage Links Colorectal Cancer and Diet High in Red Meat.
Link to Article:
https://www.cancer.gov/news-events/cancer-currents-blog/2021/red-meat-colorectal-cancer-genetic-signature
A diet heavy in red and processed meats has been related to colorectal cancer in several studies, but it’s unclear how eating cheeseburgers, hot dogs, and lamb chops may contribute to the disease’s development.
New insights might be on the way shortly. Kana Wu, M.D., Ph.D., of the Harvard T.H. Chan School of Public Health’s Department of Nutrition, designed a study to see if frequent consumption of red and processed meat, a known risk factor for colorectal cancer, may leave a specific pattern of DNA damage in colorectal tumors, known as a mutational signature.
A team of researchers, working with Dr. Wu, discovered such a pattern in the colorectal cancers of patients who reported eating a lot of red and processed meat in their diets. Specific chemicals generated in the body following the ingestion of red meat triggered this “alkylating” harm.
These mutational traces are similar to a criminal’s fingerprints left at a crime scene. Researchers can use these patterns to track down the mutations that contributed to the development of a tumor.
The identification of an alkylating mutational signature linked to red and processed meat intake "further implicates" food in the development of colorectal cancer, according to Marios Giannakis, M.D., Ph.D., also of the Dana-Farber Cancer Institute and Harvard Medical School, who co-led the study.
To reach their conclusions, the researchers examined tumor DNA from hundreds of patients with colorectal cancer who had supplied detailed information about their diet in the years leading up to their diagnosis.
Dr. Giannakis highlighted that understanding how red and processed meat may induce genetic damage that leads to colorectal cancer might lead to new ways to prevent colorectal cancer, diagnose it early, and treat it with targeted treatments. One possible strategy to prevention, he added, may be to identify those who are prone to alkylating damage and advise them to restrict their red meat consumption.
According to Dr. Straif, who was not involved in the study, the findings “shed more light” on the relationship between red and processed meat and colon cancer. "It adds to the weight of the evidence."
The evidence is growing.
For years, there has been mounting evidence linking red and processed meat to the development of colon cancer. IARC categorized processed beef as a human carcinogen (Group 1) in 2015, based on data from 800 research. This means that there is enough evidence to infer that it may cause cancer in people. Because the data for red meat was less conclusive, the International Agency for Research on Cancer categorized it as a possible carcinogen (Group 2A).
Researchers are still working to figure out how red and processed meat cause cancer. Preservatives added to processed meats, such as nitrates and nitrites, have been shown in certain studies to create chemicals that harm DNA. Other research has looked at how chemicals formed when red meat is cooked at high temperatures, such as when grilling, promote the buildup of cancer-causing mutations.
Scientists can use DNA analysis to find mutational signals that can help them figure out where the DNA damage that started a tumor’s development came from. Diverse mutational processes are reflected by different mutational signatures, which are unique patterns of DNA damage. Some mutational signatures are caused by physiological processes like DNA repair or oxidative stress, while others are caused by environmental factors like UV radiation or cigarette smoking.
Alkylating signatures are a sort of mutational signature that occurs when genetic material is destroyed by substances that cause DNA lesions (a process known as alkylation). When alkylation lesions are not adequately healed, a particular pattern of mutational damage might occur.
The use of mutational signatures to deduce correlations from epidemiologic research is becoming more common. Scientists have discovered unique mutational fingerprints linked to tobacco smoke exposure, for example.