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Body size and composition and site-specific cancers in UK Biobank: a Mendelian randomisation study

By Mathew Vithayathil, Paul Carter, Siddhartha Kar, Amy M Mason, Stephen Burgess, Susanna C Larsson

Posted 28 Feb 2020
bioRxiv DOI: 10.1101/2020.02.28.970459

Objectives: To investigate the casual role of body mass index, body fat composition and height in cancer. Design: Two stage mendelian randomisation study. Setting: Previous genome wide association studies and the UK Biobank. Participants: Genetic instrumental variables for body mass index (BMI), fat mass index (FMI), fat free mass index (FFMI) and height from previous genome wide association studies and UK Biobank .Cancer outcomes from 367 586 participants of European descent from the UK Biobank. Main outcome measures: Overall cancer risk and 22 site-specific cancers risk for genetic instrumental variables for BMI, FMI, FFMI and height. Results: Genetically predicted BMI (per 1 kg/m2) was not associated with overall cancer risk (OR 0.99; 95% confidence interval (CI) 0-98-1.00, p=0.105). Elevated BMI was associated with increased risk of stomach cancer (OR 1.15, 95% (CI) 1.05-1.26; p=0.003) and melanoma (OR 0.96, 95% CI 0.92-1.00; p=0.044). For sex-specific cancers, BMI was positively associated with uterine cancer (OR 1.08, 95% CI 1.01-1.14; p=0.015) but inversely associated with breast (OR 0.95, 95% CI 0.92-0.98; p=0.001), prostate (OR 0.95, 95% CI 0.92-0.99; p=0.007) and testicular cancer (OR 0.89, 95% CI 0.81-0.98; p=0.017). Elevated FMI (per 1 kg/m2) was associated with gastrointestinal cancer (stomach cancer OR 4.23, 95% CI 1.18-15.13, p=0.027; colorectal cancer OR 1.94, 95% CI 1.23-3.07; p=0.004). Increased height (per 1 standard deviation, approximately 6.5cm) was associated with increased risk of overall cancer (OR 1.06; 95% 1.04-1.09; p = 2.97x10-8) and most site-specific cancers with the strongest estimates for kidney, non-Hodgkin lymphoma, colorectal, lung, melanoma and breast cancer. Conclusions: There is little evidence for BMI as a casual risk factor for cancer. BMI may have a causal role for sex-specific cancers, although with inconsistent directions of effect, and FMI for gastrointestinal malignancies. Elevated height is a risk factor for overall cancer and multiple site cancers.

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