Sustained weight loss may reduce cancer risk

Although it is widely accepted that obesity is a cancer risk factor, there has been little research showing that losing weight and maintaining that loss reduce the risk of developing and possibly dying of certain cancers. A new study by Cleveland Clinic Health System (CCHS) researchers, published in the Journal of the American Medical Association (doi:10.1001/jama.2022.9009), does just that by focusing on patients who underwent bariatric surgery.

Although the biological mechanisms are still incompletely understood, it is believed by many that obesity can affect cancer development and growth by causing increased inflammation, by altering microbiota, by causing insulin resistance, and by increasing the levels of circulating insulin-like growth factor, estrogens, and adipokines.

Lead study author Ali Aminian, MD, professor of surgery at the Lerner College of Medicine and director of Cleveland Clinic’s Bariatric & Metabolic Institute, says that the researchers focused on bariatric surgery because it is an effective and long-lasting way for patients with obesity to lose weight.

The primary composite end point of this retrospective, observational, matched cohort study was the time to first incidence of one of 13 obesity-associated cancers: esophageal adenocarcinoma; renal cell carcinoma; postmenopausal breast cancer; cancer of the gastric cardia, colon, rectum, liver, gallbladder, pancreas, ovary, corpus uteri, or thyroid; and multiple myeloma. The secondary end point was cancer-related mortality.

The SPLENDID study included 5053 adult patients with obesity who underwent either Roux-en-Y gastric bypass or sleeve gastrectomy at Cleveland Clinic hospitals between 2004 and 2017. Each surgical patient was matched with five patients who did not undergo bariatric surgery. These 25,265 nonsurgical control patients were selected via a logistic regression model based on 10 potential self-reported potential confounders, including the following: race (Black, White, or other), body mass index (35–39.9, 40–44.9, 45–49.9, 50–54.9, 55–59.9, or 60–80 kg/m²), smoking history (never, former, or current), presence of type 2 diabetes, Elixhauser Comorbidity Index, Charlson Comorbidity Index, and state of residence (classified as Florida or as Ohio [because many patients were treated at CCHS facilities in those states] or as other US states combined). The median age of the patients was 46 years. Most were female (77%), and 73% were White. The median follow-up interval was 5.8 years for the bariatric surgery group and 6.1 years for patients in the nonsurgical control group.

The CCHS researchers found rather dramatic results: The bariatric surgery patients had a 32% lower incidence of obesity-associated cancer and a 48% lower risk of death from cancer than the patients in the nonsurgical control group.

At the 10-year mark, the bariatric surgery group lost 19.2% more body weight than the control group did; this corresponded to a 54.7pound difference in weight loss. The researchers also found that 96 patients in the bariatric surgery group and 780 patients in the nonsurgical control group developed an obesity-related cancer by 2021 during the 17-year follow-up period; this yielded a 10-year cumulative incidence of this primary end point of 2.9% in the bariatric surgery group and 4.9% in the nonsurgical control group.

Also, 21 patients in the bariatric surgery group (0.41%) and 205 patients in the control group (0.81%) died of cancer-related causes; these rates corresponded to 0.6 and 1.2 cancer-related deaths, respectively, per 1000 person-years of follow-up.

“What we found is striking,” said Dr Aminian in an official release from the Cleveland Clinic. “The greater the weight loss, the lower the risk of cancer.”

Dr Nissen adds, “Our findings also showed that losing weight with bariatric surgery could decrease the risk of developing precancerous lesions, such as endometrial hyperplasia, ductal carcinoma in situ of breast, colorectal polyps, and Barret’s esophagus.”

Marji McCullough, ScD, RD, senior scientific director of epidemiology research at the American Cancer Society (ACS) in Kennesaw, Georgia, who was not involved in this study, points out that it supports a growing body of literature showing that weight loss among those with morbid obesity may reduce the risk of developing cancer, especially obesity-related cancers. “Many questions remain, however,” she says. “Is this association causal? What are the mechanisms? Should certain patients be prioritized for bariatric surgery? How much weight loss is required to see an effect?” Dr McCullough also notes that although long-term weight loss without surgery typically does not result in as dramatic of a weight loss, other observational studies suggest that more modest weight loss may also lower the risk of certain obesity-related cancers.

Lauren R. Teras, PhD, Dr McCullough’s colleague at the ACS and a senior scientific director of epidemiology in the ACS’s Department of Population Science, notes that the study did not find a lower risk of breast cancer with bariatric surgery. “This may be due to the young age of the participants, who were age 46 on average at study entry, with a median follow-up of about six years. The increased risk of breast cancer for obesity is restricted to postmenopausal breast cancer only.” Thus, a study that enrolled older patients or one with much longer follow-up might have shown even more favorable results, including a reduction in breast cancer incidence and mortality rates.

“When considering the broader implications of the study, it’s important to note that results from bariatric surgery studies may not be applicable to the general population,” Dr Teras adds. “Bariatric surgery patients undergo preoperative health screening, have an extremely high body weight before surgery, lose extremely large amounts of weight in a short period of time, and undergo hormonal and metabolic changes from the surgery that induce more pronounced biological responses.”

Dr McCullough notes that criteria for evaluating who is a good candidate for bariatric surgery exist from many sources, including the American Society for Metabolic and Bariatric Surgery and the National Institute of Diabetes and Digestive and Kidney Diseases: “For general guidance on cancer prevention, clinicians can refer to the American Cancer Society Guideline for Diet and Physical Activity for Cancer Prevention [https://www.cancer.org/healthy/eat-healthy-get-active/acs-guidelines-nutrition-physical-activity-cancer-prevention/guidelines.html].”