PT  - JOURNAL ARTICLE
AU  - Matteo Di Giovannantonio
AU  - Benjamin HL Harris
AU  - Ping Zhang
AU  - Isaac Kitchen-Smith
AU  - Lingyun Xiong
AU  - Natasha Sahgal
AU  - Giovanni Stracquadanio
AU  - Marsha Wallace
AU  - Sarah Blagden
AU  - Simon Lord
AU  - David Harris
AU  - Adrian H.L. Harris
AU  - Francesca M. Buffa
AU  - Gareth L. Bond
TI  - Heritable genetic variants in key cancer genes link cancer risk with anthropometric traits
AID  - 10.1136/jmedgenet-2019-106799
DP  - 2021 Jun 01
TA  - Journal of Medical Genetics
PG  - 392--399
VI  - 58
IP  - 6
4099  - http://jmg.bmj.com/content/58/6/392.short
4100  - http://jmg.bmj.com/content/58/6/392.full
SO  - J Med Genet2021 Jun 01; 58
AB  - Background Height and other anthropometric measures are consistently found to associate with differential cancer risk. However, both genetic and mechanistic insights into these epidemiological associations are notably lacking. Conversely, inherited genetic variants in tumour suppressors and oncogenes increase cancer risk, but little is known about their influence on anthropometric traits.Methods By integrating inherited and somatic cancer genetic data from the Genome-Wide Association Study Catalog, expression Quantitative Trait Loci databases and the Cancer Gene Census, we identify SNPs that associate with different cancer types and differential gene expression in at least one tissue type, and explore the potential pleiotropic associations of these SNPs with anthropometric traits through SNP-wise association in a cohort of 500,000 individuals.Results We identify three regulatory SNPs for three important cancer genes, FANCA, MAP3K1 and TP53 that associate with both anthropometric traits and cancer risk. Of particular interest, we identify a previously unrecognised strong association between the rs78378222[C] SNP in the 3' untranslated region (3'-UTR) of TP53 and both increased risk for developing non-melanomatous skin cancer (OR=1.36 (95% 1.31 to 1.41), adjusted p=7.62E−63), brain malignancy (OR=3.12 (2.22 to 4.37), adjusted p=1.43E−12) and increased standing height (adjusted p=2.18E−24, beta=0.073±0.007), lean body mass (adjusted p=8.34E−37, beta=0.073±0.005) and basal metabolic rate (adjusted p=1.13E−31, beta=0.076±0.006), thus offering a novel genetic link between these anthropometric traits and cancer risk.Conclusion 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 genetic basis for linking these human phenotypes.Data used in this study are either available in public, open access repositories, or may be obtained from a third party. For UK Biobank data, please apply to the UK Biobank Consortium through the approved process, details can be found here: https://www.ukbiobank.ac.uk/