Abstract
According to an analysis of more than 1,000 epidemiologic studies, being overweight or obese increases the risk of eight cancers: stomach, liver, gallbladder, pancreas, ovary, and thyroid cancers, multiple myeloma, and meningioma. Researchers initially identified five other malignancies linked to excess body weight in 2002, including breast and endometrial cancers.
A working group convened by the International Agency for Research on Cancer (IARC), part of the World Health Organization, has linked eight additional cancers with being overweight, defined as an adult body-mass index (BMI) of 25.0–29.9, or obese, a BMI of 30 or higher.
In 2002, another IARC working group associated five cancers—colon cancer, breast cancer, endometrial cancer, esophageal adenocarcinoma, and renal cell carcinoma—with being overweight or obese. The new report adds stomach, liver, gallbladder, pancreas, ovary, and thyroid cancers to the list, as well as multiple myeloma and meningioma (N Engl J Med 2016;375:794–8).
After reviewing more than 1,000 epidemiologic studies on cancer risk and excess body fat, the group concluded that the risks were similar for men and women and consistent across different geographic regions. They noted a particularly pronounced association between obesity and esophageal adenocarcinoma: The risk was nearly five times greater for adults with a BMI of 40 or higher, compared with those of normal weight.
Graham Colditz, MD, DrPH, the group's chair and a cancer prevention expert at Washington University School of Medicine in St. Louis, MO, explains that obesity promotes chronic inflammation and various metabolic and endocrine abnormalities, including the overproduction of estrogen and testosterone, as well as altered insulin signaling, all of which influence carcinogenesis.
“We'd like to find potentially modifiable risk factors—for instance, druggable pathways—to benefit people who may not be able to easily change other lifestyle-related factors for various reasons,” he says.
Nonetheless, intentional weight loss is important and beneficial, Colditz emphasizes. Data from follow-up observations of women who underwent bariatric, or stomach size-reducing, surgery suggest that losing weight significantly lowers the risk of endometrial and breast cancers. “It's a signal,” he says. “Still, because most people who lose weight don't keep it off, accurately measuring the long-term beneficial effects has been difficult. We'd really like to gather more evidence from larger studies of sustained weight loss.”
To that end, Colditz hopes a recently launched clinical trial at Dana-Farber Cancer Institute in Boston, MA, will be fruitful. Oncologist Jennifer Ligibel, MD, has partnered with Fitbit to recruit approximately 3,200 overweight or obese women with early-stage breast cancer through oncology practices across the United States and Canada. Participants will receive fitness-tracking devices and phone counseling to assist in meeting their weight-loss goals; they'll also be followed to assess whether losing weight prevents disease recurrence.
Overall, Colditz sees similarities between documenting the roles of excess body fat and smoking, respectively, in cancer risk. “It took a while for us to understand that smoking is associated with multiple cancers, not just lung, due to the accumulation of toxins over a lifetime,” he observes. “I think the same will be true as we learn more about the molecular mechanisms affected by being overweight or obese.” –Alissa Poh
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