The number of cancers linked by scientific evidence to obesity has increased to 13, according to a recent special report by the International Association for Research on Cancer (IARC) Handbook Working Group (Lauby-Secretan B, et al. N Engl J Med. 2016;375:794-798). The total number of cancers linked to obesity include 5 identified in a previous IARC review—colorectal, esophageal, kidney, postmenopausal breast, and endometrial. The updated review identified sufficient evidence to indict obesity as a causal and preventable factor in 8 additional cancers, including gastric cardia, liver, gallbladder, pancreas, ovarian, meningioma, and thyroid cancers, as well as multiple myeloma.
Across the 13 different cancer types, the relative risk imposed by the highest body mass index (BMI) category compared with the normal BMI class ranged from 1.1 for thyroid, postmenopausal breast, and ovarian cancer to 7.1 for uterine cancer. The magnitude of risk ranged from 1.3 to 1.8 for all the remaining cancers but for esophageal cancer. Obesity increased the risk for esophageal adenocarcinoma by a factor of 4.8.
“The bottom line is that this rigorous review has added another 8 cancers for which we are convinced there is sufficient evidence for a cause-and-effect relation between obesity and cancer,” Graham A. Colditz, MD, DrPH, Chair, IARC Handbook Working Group, and Chief, Division of Public Health Sciences, Washington University School of Medicine, St Louis, told Value-Based Cancer Care. “This broader list goes part way toward helping raise awareness about the importance of obesity as a cancer risk. This list makes the point that we’re not just talking about a few cancers that affect a limited number of people.”
Using a BMI value of ≥30 kg/m2 to define obesity, an estimated 640 million adults worldwide were obese in 2014, a 6-fold increase since 1975, according to the IARC. In addition, the IARC reported that in 2013, 110 million children and adolescents were classified as obese, a 2-fold increase since 1980. In 2014, the estimated age-standardized incidence of obesity was approximately 11%, 15%, and 5% in men, women, and children, respectively.
Substantial geographic variation exists in obesity frequency. For example, the Centers for Disease Control and Prevention has estimated the prevalence of obesity in the United States as >36.5% among adults, and 17% among children and adolescents. Obesity and being overweight caused an estimated 4.5 million deaths in 2013, according to the IARC report.
For the reassessment of the association between obesity and cancer, an IARC working group of 21 international experts reviewed more than 1000 epidemiologic studies. Because the majority of data came from observational studies of cancer risk and excess body fatness, the evaluations did not take into account risk reductions associated with preventive interventions.
The panel found significant associations between BMI and risk for cancer of the colon, rectum, gastric cardia, liver, gallbladder, pancreas, kidney, and esophagus. Relative risks derived from meta-analyses or pooled analyses ranged from 1.2 to 1.5 for being overweight, and 1.5 to 1.8 for obesity. Of note, the relative risk for esophageal cancer was up to 4.8 for a BMI ≥40 kg/m2.
“When studies from different geographic regions were available…results were consistent across regions,” members of the working group reported. “Stratification according to sex, when available, generally showed similarly increased risks among men and women.”
Positive associations have been previously reported for adult BMI and postmenopausal breast cancer. Most studies have yielded a relative risk of approximately 1.1 per 5 BMI units. In contrast, consistent inverse associations have been observed for obesity and premenopausal breast cancer risk.
The data for multiple myeloma showed a relative risk that increased with the severity of obesity. The relative risk was 1.2 for being overweight and for class 1 obesity (BMI 30.0-34.9 kg/m2), and 1.5 for class 2 or 3 obesity (BMI 35.0-39.9 kg/m2, and BMI ≥40.0 kg/m2, respectively).
The panel observed a “strong dose−response relationship” between high BMI and endometrial cancer. The relative risk was 1.5 for being overweight 2.5 for class 1 obesity, 4.5 for class 2 obesity, and 7.1 for class 3 obesity.
The data showed a modest positive association between BMI and ovarian cancer, represented by a relative risk of 1.1.
The panel reviewed data for 8 other cancer types, but found the evidence insufficient to make a determination regarding associations between their risk and being overweight or obese. Evidence was considered insufficient because of limited, inconsistent, or nonexistent data suggesting an association.
The working group also found the data too limited to draw conclusions for breast cancer in men, fatal prostate cancer, and diffuse large B-cell lymphoma. Data were judged inadequate for squamous-cell carcinoma of the esophagus, as well as gastric noncardia, glioma, extrahepatic biliary tract, lung, cutaneous melanoma, testis, and urinary bladder cancers.
With the accumulation of additional studies and data, some of the cancers with insufficient evidence could eventually join the list of cancers that have convincing evidence of a causal association with obesity, said Dr Colditz.
