Obesity Raises Second Cancer Risk in Survivors

Clara Bodelon, PhD, MS

Credit: American Cancer Society

Results of a cohort study of 26,894 older nonmetastatic cancer survivors highlight the importance of promoting healthy weight management and increasing awareness of the risk of second cancers among cancer survivors and their healthcare providers.

The study, published in JAMA Network Open, showed that those with overweight (42.8%) or obesity (17.2%) at their first cancer diagnosis faced a significantly increased risk of developing a second cancer. Obesity, specifically, was linked to a 34% higher risk of any second cancer and a 78% greater risk of obesity-related cancers.

Due to early detection, improved treatment option and population growth, the number of cancer survivors has significantly increased in recent decades. However, this population faces a higher risk of developing another primary cancer in comparison to the general population, with 20% of all new cancer diagnoses classified as malignant neoplasms.

“Understanding the causes of second primary cancers could have important public health and clinical implications,” wrote a team of investigators led by Clara Bodelon, PhD, MS, senior principal scientist at the American Cancer Society. “Prior studies examining the causes of second cancers among survivors of childhood cancers have found that treatment and genetics play major roles. However, little is known about the causes of second primary cancers among survivors of adult-onset cancers.”

To determine the link between body weight and an increased risk of second cancers, investigators used data from the Cancer Prevention Study II (CPS-II) Nutrition cohort, a large prospective study of adults living in the United States. Patients were originally invited to respond to a survey in 1992, followed by biennial surveys from 1997 through 2017. Eligible patients had received a first primary nonmetastatic invasive cancer diagnosis between 1992 and 2015.

The primary endpoints were an obesity-related second cancer or second primary cancer diagnosis, which were reported in the surveys and confirmed through medical records. Body mass index (BMI) was assessed at up to two years post diagnosis, between two and five years, and again at more than five years. Obesity-related cancers included colon, liver, pancreas, gallbladder, kidney, ovary, thyroid, postmenopausal breast cancer, gastric cardia, esophageal adenocarcinoma and multiple myeloma.

Among the patients included in the study, more than half (59.2%) were male, 97.6% were White and the mean age at first diagnosis was 72.2 years.

During the follow-up period (median time of 7.9 years), 13.9% of patients received a second primary cancer diagnosis, of which 33.2% were obesity-related. Additionally, every 5-kg/m2 increase in BMI was linked to a 13% increased risk of a second cancer.

Survivors classified as overweight had a 15% increased risk of second primary cancer compared with cancer survivors whose BMI was normal. This jumped to a 34% increased risk in patients with obesity. Patients with overweight were 40% more likely to develop obesity-related second primary cancers, while patients with obesity saw a 78% increased risk.

Investigators noted the large cohort, prospective design and long-term follow-up as strengths of the study. They also excluded participants with metastatic disease, as they could experience disease-related weight loss. However, using BMI to measure of body fat was considered a limitation, as this measurement cannot differentiate between fat and lean mass. Additionally, there is a possibility of unmeasured or residual confounding due to the observational nature of the study.

“Given the high prevalence of overweight and obesity among cancer survivors, it is important to promote survivorship care guidelines recommending weight management and increase awareness of second cancers among physicians and cancer survivors,” investigators concluded.