Intervention Curbs Obesity-Related Cancers in T2D: Look AHEAD

An intensive lifestyle intervention aimed at weight loss lowers the incidence of obesity-related cancers in adults with either overweight or obesity, and type 2 diabetes, finds an analysis of findings from the Look AHEAD (Action for Health in Diabetes) trial.

The incidence of obesity-related cancers fell by 16% for participants on the lifestyle intervention. This is the first trial to date to have evaluated the effects of such an intervention for weight loss on the risk of incident cancer or cancer mortality in adults with high body mass index (BMI) at study start, according to the results published online August 24 in the journal Obesity.

The investigators, led by Hsin-Chieh Yeh, PhD, acknowledge that the result is not statistically significant but, "this finding provided evidence that patients with obesity can reduce their cancer risk through weight loss," they write.

"Healthcare providers should be encouraged to provide [such] counseling or refer patients with obesity to intervention programs that help people manage their weight," said Yeh, associate professor of medicine, epidemiology, and oncology at Johns Hopkins University, Baltimore, Maryland, in a press release. "Moreover, establishing an environment with easier access to healthy food and physical activities is the foundation of obesity and cancer prevention."

Prior to this study, evidence that weight loss reduces cancer incidence was observational only and established association rather than causality. This randomized clinical trial provides the data needed to determine the causal effect between intentional weight loss and reduced cancer incidence and mortality.

The lowering of risk of obesity-related cancer incidence by 16%, was "a reduction that would be clinically valuable," Justin C. Brown, PhD, and Anne McTiernan, MD, write in an invited commentary. Brown is director of the Cancer Metabolism Program at Pennington Biomedical Research Center in Baton Rouge, Louisiana, and McTiernan is a professor of epidemiology at Fred Hutchinson Cancer Research Center in Seattle, Washington.

They also point out that "the effects of weight loss on cancer risk may differ by molecular tumor subtype, sex, age, race, or ethnicity," and that the trial "was limited to individuals with type 2 diabetes."

The Look AHEAD Substudy

Obesity is associated with the risk of several types of cancer, including cancers of the colon, gastric cardia, liver, gallbladder, pancreas, kidney, esophagus and endometrium. To investigate this relationship further, the Look AHEAD trial aimed to determine whether an intensive lifestyle intervention aimed at weight loss lowers cancer incidence and mortality.

A total of 4859 participants with type 2 diabetes and overweight or obesity were assigned to a 10-year intensive lifestyle intervention targeting a weight loss of 7% of body weight, or to a diabetes support and education group. The three key cancer outcomes included overall cancer incidence, obesity-related cancer incidence, and any of 13 prespecified cancers associated with obesity and overall cancer mortality.

The intensive lifestyle intervention was designed to achieve and maintain weight loss of at least 7% through caloric intake reduction and increased physical activity. The program included both group and individual counseling sessions, occurring weekly during the first 6 months, followed by three sessions monthly for the next 6 months, and twice-monthly contact and regular refresher group series and campaigns in years 2 to 10.

Participants in the diabetes support and education group received three group sessions per year and focused on diet, exercise, and social support that were provided during years 1 through 4. In following years, the frequency was reduced to one session annually.

Key Findings

After a median follow-up of 11 years, the intensive lifestyle intervention was not associated with significant reduction in overall cancer incidence or cancer mortality, most likely because of the insufficient power for either outcome, the investigators say, adding that "the 95% CI did cross 1.0, but that was likely because of the insufficient sample size.".

Incidence of obesity-related cancers decreased in those in the intervention group with a hazard ratio (HR) of 0.84 (95% CI, 0.58-1.04). "Because we did not collect data on the specific region of a tumor (eg, cardia of stomach, esophageal adenocarcinoma, wherein associations are very strong with obesity), the misclassification may lead to underestimating the intervention effect," they add.

At 1 year, the difference in weight loss between the intervention group and the diabetes support and education group was 7.9% (−8.6% vs. −0.7%); after 12 years, this effect waned, to 1.9% (−6.5% vs. −4.6%).

After a median follow-up of 11 years, incident cancer between the two groups (intervention vs diabetes support and education group) had an HR of 0.93 (95% CI, 0.80 - 1.08; P = .32), so no significant difference. Cancer-specific mortality between the two groups had an HR of 0.92 (95% CI, 0.68 - 1.25; P = .59).

The findings from the Look AHEAD Research Group will inform the next generation of studies on obesity and cancer prevention and control, conclude Brown and McTiernan in their commentary. "Interpreting the findings from this randomized trial in the context of current preclinical, observational, and experimental studies of biomarker end points is consistent with the hypothesis that obesity has a causal, and plausibly reversable, effect on cancer risk."

Yeh has disclosed no relevant financial relationships. Brown reports receiving grants paid to his institution from the National Cancer Institute, American Institute for Cancer Research, and the Susan G. Komen Foundation. McTiernan reports receiving grants paid to her institution from the National Cancer Institute and Breast Cancer Research Foundation.

Obesity. Published online August 24, 2020. Full text, Editorial

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