Excess body weight at first cancer diagnosis increases risk of second cancer

By Dr. Sushama R. Chaphalkar, PhD.Reviewed by Benedette Cuffari, M.Sc.Sep 22 2024

Cancer survivors who are overweight or obese are at higher risk for developing secondary cancers, urging the need for focused weight management strategies in survivorship care plans.

Study: Excess Body Weight and the Risk of Second Primary Cancers Among Cancer Survivors. Image Credit: PeopleImages.com / Yuri A / Shutterstock.com

A recent study published in JAMA Network Open reveals that adults who were overweight or obese at the time of their first cancer diagnosis are more likely to develop a second primary cancer, particularly an obesity-related cancer.

What causes secondary cancers in cancer survivors?

Although the population of cancer survivors has grown significantly, survivors face increased risks, including a higher likelihood of developing second primary cancers. These subsequent cancers account for about 20% of all new cancer diagnoses annually and are a leading cause of illness and mortality among survivors.

While treatment and genetics are known contributors to second cancers in childhood cancer survivors, less is understood about adult cancer survivors. Only a small percentage of second cancers in adults can be attributed to radiotherapy; therefore, lifestyle factors, environmental exposures, and genetics likely have an important role in this association.

Prior studies, particularly registry-based analyses, suggest an association between obesity-related cancers and increased risk of second cancers. However, these studies lack the consideration of risk factors, confounding factors, and individual-level data, which can lead to potential bias.

To date, no comprehensive prospective cohort study has thoroughly examined the role of obesity in second primary cancers across various cancer types in adult survivors.

About the study

The Cancer Prevention Study II Nutrition Cohort included 26,894 participants diagnosed with nonmetastatic primary cancer, who had a mean age of 72.2 years, 85.6% of whom were 65 years of age or older. Study participants provided self-reported demographic and lifestyle information, including body mass index (BMI), which was calculated prior to and at intervals after the first cancer diagnosis.

Cancer diagnoses were verified through medical records and cancer registries, with follow-ups from 1992 to 2017. The study excluded participants with BMI values less than 18.5 kg/m², those with in situ or distant-stage disease, those diagnosed with a second primary cancer within 60 days of their first primary cancer diagnosis, and those over 85 years at diagnosis.

Treatment information, including surgery, chemotherapy, and radiation, was obtained from Medicare claims and self-reporting. Second primary cancers were identified following coding rules from surveillance, epidemiology, and end results (SEER).

The researchers were particularly interested in obesity-related cancers, including esophageal adenocarcinoma, postmenopausal breast cancer, gastric cardia, colon, rectum, liver, gallbladder, pancreas, corpus uteri, ovary, kidney, meningioma, thyroid, and multiple myeloma due to established causal links between excess body fat and cancer risk.

Statistical analysis was conducted using cumulative incidence function, Gray test, Cox proportional hazard models, Schoenfeld residuals test, and Fine and Gray regression models.

Study findings

The most common initial diagnoses were prostate, breast, and colorectal cancers, which were diagnosed among 35%, 19.1%, and 9.5% of the study cohort, respectively. Most survivors never smoked or had discontinued smoking.

During a median follow-up of 7.9 years, 13.9% of study participants developed a second cancer, 33.2% of which were obesity-related. Higher BMI was significantly associated with an increased incidence of second cancers.

Each five kg/m² increase in BMI raised the risk of any second cancer by 13% and obesity-related second cancers by 28%. More specifically, a five kg/m² increase in BMI was associated with a 42% higher risk of second colorectal cancer and a 70% increased risk of second kidney cancer. Subgroup analyses revealed consistent results across age, sex, and smoking status, with death as a competing risk considered in the analysis.

Strengths and limitations

The current study is the first to examine the relationship between BMI and second primary cancers in older cancer survivors. It is strengthened by its large and prospective cohort, systematic risk factor data collection, long-term follow-up, timely exposure ascertainment, exclusion of metastatic disease, and consistent associations across various survivor groups.

However, the study is limited by a potential underestimation of associations due to the exclusion of multiple primary cancers at the same site, reliance on BMI as a measure of body fat, incomplete treatment data, and the possibility of unmeasured confounding in this observational design.

Conclusions

Older survivors of nonmetastatic cancer with overweight or obesity at their first diagnosis are at an increased risk of developing secondary cancers, particularly those related to obesity. Given the prevalent issue of overweight and obesity among cancer survivors, the study findings highlight significant public health implications and could guide evidence-based survivorship guidelines aimed at reducing the risk of second primary cancers.

In the future, implementing weight loss strategies and enhancing awareness of second cancer risks among healthcare providers for cancer survivors need to be prioritized.