Colorectal cancer remains the third-leading cause of cancer deaths among women in the United States. Diabetes has been identified as a colon cancer risk factor, but the mechanisms aren’t completely understood. For this population-based cohort study, researchers examined data from 37,695 participants of the Iowa Women’s Health Study (IWHS), which enrolled women ages 55–69 in 1986 and remains ongoing. Of these women, 2,361 reported a diagnosis of Type 2 diabetes and 1,200 developed colorectal cancer.
To find the links between colorectal cancer and diabetes, the researchers worked with regional pathology laboratories to obtain tumor tissue samples from IWHS participants who were diagnosed with colorectal cancer. They linked the tissue samples with other IWHS data, looking for cancer pathways and risk factors, and whether those risk factors were associated with three different molecular markers: microsatellite instability (MSI), CpG island methylation (CIMP), and BRAF gene mutations.
“Diabetes was more strongly associated with the MSI-high, CIMP-positive and BRAF-mutation cancer subtypes in this group of older women,” says Mayo Clinic gastroenterologist Paul Limburg, M.D. Dr. Limburg explains that diabetes appeared to confer a greater than twofold increase in risk for these molecularly-defined tumors, compared to women without diabetes.
“Knowing that diabetic women have these findings should help to facilitate more appropriate colorectal cancer prevention and treatment options,” says Anthony Razzak, M.D., a Mayo Clinic research fellow and presenter at the conference. “Our findings may lead to new strategies for colon cancer screening, chemotherapy and chemoprevention in women with diabetes.”
“From a research perspective, this information allows us to clarify how environmental exposures and other risk factors might effect tumor formation at a molecular level,” says Dr. Razzak. For future projects, the researchers will work to understand more about the biology of colorectal cancer and how it is influenced by diabetes, as well as other chronic conditions and exposures. They hope to use that information to improve patient care.
“Unfortunately, diabetes and colon cancer are both very common in the United States, so making links between these disorders has substantial public health implications,” says Dr. Limburg. Mayo Clinic’s Division of Gastroenterology and Hepatology has been ranked No. 1 in the U.S. News & World Report Honor Roll of Top Hospitals since the rankings began 20 years ago. Collaboration The study was funded by the National Cancer Institute. Additional Mayo Clinic co-authors are Amy Oxtenko, M.D.; Robert Vierkant; Lori Tillmans; Alice Wang; Susan Slager, Ph.D; Thomas Smyrk, M.D.; Stephen Thibodeau, Ph.D.; and James Cerhan, M.D., Ph.D. Co-authors from other institutions are Daniel Weisenberger, Ph.D., and Peter Laird, Ph.D., both of the University of Southern California Epigenome Center; Charles Lynch, M.D., Ph.D., University of Iowa College of Public Health, Iowa City; Kristin Anderson, Ph.D., and Lisa Harnack, Ph.D., both of the University of Minnesota Cancer Center, Minneapolis; Robert Haile, Ph.D., of the University of Southern California School of Medicine, Los Angeles; and John Potter, M.D., Fred Hutchinson Cancer Research Center, Seattle.
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