Background: Within the normal BMI (body mass index (BMI) of 18.5-24.9kg/m2) category, some individuals may be at increased risk of developing obesity-related cancers. Towards this end, studies have shown positive associations between body fat, particularly in the abdominal region, and cancer-associated metabolic disturbances among normal weight individuals. However, little is known about the association between body fat distribution and risk of obesity-related cancers among normal weight individuals. Thus, in this study, we examined the association of overall and central adiposity, assessed using bioelectrical impedance (BIA)-derived and anthropometric measures, with risk of selected obesity-related cancers among normal weight persons.

Methods: The study included normal weight individuals aged 40-70 years who were enrolled in the UK Biobank cohort between 2006 and 2010. BIA-derived and anthropometric body fat measures were taken at baseline by trained staff. Incident tumors were ascertained via linkage to UK cancer registries. Multivariable Cox proportional hazards regression models were used to estimate the hazard ratios (HR) and 95% confidence intervals (CI) for the associations of the body fat measures with risk of cancers of the breast, endometrium, ovary, colorectum, pancreas, and kidney, and with multiple myeloma.

Results: The overall incidence of obesity-related cancers was 2.2 per 1000 person-years of follow-up (N= 2364 incident obesity-related cases among 152,489 subjects with a median follow-up time of 7 years). All measures of central and peripheral adiposity demonstrated linear positive dose-response relationships with risk of postmenopausal invasive breast cancer and with endometrial cancer. For all of the body fat measures, postmenopausal women in the highest quartile showed increased invasive breast cancer risk, after adjusting for potential confounders, compared to women in the lowest quartile, with hazard ratios ranging from 1.29 (95% CI: 1.11-1.50) for the ratio of trunk fat to leg fat mass to 1.59 (95% CI: 1.31-1.93) for trunk fat mass index (TFMI; calculated as trunk fat mass (kg)/height (m)2). For endometrial cancer, only the TFMI (HR: 1.80, 95% CI:1.12-2.88) and waist circumference (HR: 1.70, 95% CI: 1.04-2.80) were positively associated with risk. A waist-to-hip ratio in the highest quartile was also positively associated with colorectal cancer risk among males (HR: 1.56, 95% CI: 1.03-2.37). None of the body fat measures were associated with risk colorectal cancer risk among women or with risk of the remaining cancers.

Conclusion: The findings of this study suggest that elevated levels of central and/or overall adiposity may be associated with increased risk of postmenopausal breast cancer, endometrial cancer and probably colorectal cancer (males), among normal weight individuals. Evaluating body composition in those with a normal BMI can potentially identify individuals at increased risk for cancer providing an opportunity for interventions to reduce risk.

Citation Format: Rhonda S. Arthur, Mimi Kim, Andrew Dannenberg, Thomas Rohan. Measures of overall and central adiposity in relation to risk of obesity-related cancers among normal weight men and women in the UK Biobank [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 3483.