Study: High BMI + Certain Genetic Makeup = Sharp Increase in Women's Colorectal Cancer Risk

For women with a certain genetic makeup, being overweight or obese significantly raises the risk for colorectal cancer, according to a recent study published in JNCI: Journal of the National Cancer Institute.

Researchers know that being overweight or obese is a risk factor for colorectal cancer and that it affects risk more strongly in men than in women. But how body weight affects colorectal cancer risk is complicated.

In this study, researchers looked at whether the risk was affected by the interaction of body mass index (BMI, a measure of obesity based on height and weight) with variations in a gene called SMAD7 that is linked with colorectal cancer. They found that in women with certain variants in the SMAD7 gene, a higher BMI was linked with a higher risk of colorectal cancer whereas there weren’t any statistically significant interactions in men.

One specific variant of the SMAD7 gene in women, called the CC-genotype, had the strongest interaction with BMI—a 24% increase in risk for colorectal cancer for every 5-point increase in BMI. Women with another variant, the CT genotype, had a 14% increase in risk, and those with the TT genotype had a 7% risk increase.

“We’ve extended a very common and well-established risk factor with obesity, or high BMI, by showing how that risk factor may interact with genetic variants in a very robust and powerful way for women,” said American Cancer Society (ACS) epidemiologist Peter Campbell, PhD, the lead author of the study.  

Previous studies have shown that a high BMI by itself raises the risk of colorectal cancer in men more than in women, and the ACS research team verified this finding. Studying BMIs of about 14,000 adults with colorectal cancer and 14,000 adults without it, the researchers found that men had a 26% increased risk for every 5-point increase in BMI, from the low end of the normal range (a BMI of 18.51) to a very heavy BMI of about 60. Women had a 14% increased risk for each 5-point increase in BMI.

Previous research has also found that certain inherited genetic variants increase the risk of colorectal cancer. This study is unique, Campbell said, because the researchers had the BMIs for all 28,000 participants as well as their genetic information.

Adding obesity as an environmental exposure on top of a high-risk genetic makeup, they discovered, is like a second hit in women, Campbell said.

“These results can serve as a reminder that obesity is linked with a lot of health problems, including cancer,” he said.