Abstract 3434: Effect modification by levels of sex hormones in the association between adiposity and cancer incidence in the UK Biobank

Abstract

Abstract Introduction: The association between adiposity and cancer risk differs between sexes for some cancer types. Methods: We prospectively examined adiposity in relation to cancer incidence according to sex hormones in the UK Biobank. Adiposity was assessed by body mass index (BMI) and visceral adipose tissue (VAT), the latter predicted using determinants of age, height, weight, hip circumference, waist circumference, and race. Serum sex hormone binding globulin (SHBG), testosterone, and estradiol were measured using a biochemistry assay and were classified as high or low based on median levels. Cancer incidence was ascertained using ICD-10 codes through cancer registry linkage. For cancer types showing a sex difference in the association between adiposity and cancer incidence, we assessed multiplicative and additive interaction with sex hormones in men and women separately and corrected for multiple testing using false discovery rate. We used Cox regression to calculate the multivariable hazard ratio (HR) of cancer per increase between the 90th to 10th percentile of adiposity (BMI or predicted VAT). Results: During a median follow-up of 13.1 years, we documented 23,964 and 21,045 incident cancer cases among 217,460 men and 256,163 women, respectively. Adiposity showed a much stronger association with higher risk of colorectal, esophageal, and liver cancers in men than women. In men, BMI was more strongly associated with higher risk of colorectal cancer in low vs. high levels of SHBG (HR (95%CI) of 1.47 (1.31-1.64) vs. 1.12 (0.94-1.33) (adjusted Pinteraction = 0.027). In contrast, BMI showed a stronger association in high vs. low levels of SHBG with esophageal (HR = 2.39 vs. 1.62) and liver cancers (HR = 3.24 vs 1.96) in men (adjusted Pinteraction = 0.038 and 0.027, respectively). Among women, BMI was associated with a higher risk of esophageal cancer in those with low SHBG (HR=1.68) but not in those with high SHBG (HR=0.64) (adjusted Pinteraction = 0.025). Similar patterns were observed for predicted VAT. Men with high SHBG levels and high adiposity (BMI and predicted VAT) had 7.63 (5.08-11.46) and 8.92 (5.72 to 13.90), respectively, times higher risk of liver cancer compared to men with low SHBG levels and low adiposity. No effect modification by estradiol or testosterone was detected for any of the cancers studied. Conclusions: The association between adiposity and colorectal, esophageal, and liver cancer differed by sex. SHBG may be an important factor underlying these differences. Citation Format: LeeAnn Lucas, Yujia Lu, Edward L. Giovannucci, Mingyang Song. Effect modification by levels of sex hormones in the association between adiposity and cancer incidence in the UK Biobank [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3434.