Heritable genetic variants in key cancer genes link cancer risk with anthropometric traits

Abstract

Inherited genetic variants in tumour suppressors and oncogenes can increase the cancer risk, but little is known about their influence on anthropometric traits. Through the integration of inherited and somatic cancer genetic data, we define functional single nucleotide polymorphisms (SNPs) associated with cancer risk and explore potential pleiotropic associations with anthropometic traits in a cohort of 500,000 individuals. We identify three regulatory SNPs for three important cancer genes that associate with both anthropometric traits and cancer risk. We describe a novel association of a SNP in TP53 (rs78378222) with height, lean body mass measures and basal metabolic rate, as well as validating its known associations with brain and non-melanomatous skin cancer susceptibility. Our results clearly demonstrate that heritable variants in key cancer genes can associate with both differential cancer risk and anthropometric traits in the general population, thereby lending support for a role of genetics in linking these human phenotypes.