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Nurses’ Health Study illuminates colorectal cancer risk


An increasing body mass index was associated with a higher risk for colorectal cancer with a specific molecular characteristic, and, inversely, physical activity was linked to a decreased risk, according to data from the Nurses’ Health Study and Health Professionals Study.

“We know that exercise and avoiding obesity decrease colorectal cancer risk, but little is known about why,” Shuji Ogino, MD, PhD, associate professor pathology at Dana-Farber Cancer Institute and associate professor in the Department of Epidemiology at Harvard School of Public Health in Boston, said in a news release.

Ogino and colleagues used data from more than 100,000 women from the Nurses’ Health Study and more than 45,000 men in the Health Professionals Study to examine whether there was an association between body mass index or exercise activity and colorectal cancer risk according to expression status of the biomarker CTNNB1.

Among the study population, 2,263 individuals were diagnosed with colorectal cancer during follow-up. Tumor CTNNB1 expression data were available for 861 of these individuals, and 54% of these tumors were negative and 46% positive for CTNNB1.

Increasing BMI by increments of five kilograms per square meter was associated with a 34% higher risk for CTNNB1-negative cancer, but was not associated with CTNNB1-positive cancer. In contrast, increasing physical activity level was associated with a significantly lower risk for CTNNB1-negative cancer, and was not associated with CTNNB1-positive cancer.

“Our results provide additional evidence for a causal role of obesity and a physically inactive lifestyle in a specific molecular subtype of colorectal cancer,” Ogino said. “If physicians are able to identify individuals who are prone to develop CTNNB1-negative cancer, then it would be possible to strongly recommend physical activity.”

In addition, the data indicated that CTNNB1 could be a potential target for chemoprevention and treatment, according to Ogino. He called for more population-based, large-scale databases to facilitate molecular pathological epidemiology research.

“Currently, most population-based studies do not take tumor heterogeneity into consideration, and typically colon cancer is treated as a single disease,” Ogino said. “We need to integrate molecular pathology and epidemiology in education and research to facilitate integrative science and improve public health.”

The study appeared Feb. 26 on the website of Cancer Research, a journal of the American Association for Cancer Research. The study abstract is available at


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