Abstract A069: TRPV6 as a putative genomic susceptibility locus influencing racial disparities in cancer

Abstract

Abstract It is well established that African Americans exhibit higher incidence, higher mortality, and more aggressive forms of some cancers, including those of breast, prostate, colon, stomach, and cervix. Here we examine the ancestral haplotype of the TRPV6 calcium channel as a putative genomic factor in this racial divide. The minor (ancestral) allele frequency is 60% in those of African Ancestry, but between 1 and 11% in all other 1000 Genomes populations. Recent research on TRPV6 structure/function, its association with specific cancers, and the evolutionary-ecological conditions which impacted selection at its locus are synthesized to provide evidence for the TRPV6 haplotype as a germline susceptibility locus in cancer. Examination of a recently-proposed model for TRPV6 Ca2+-dependent inactivation, as it relates to the haplotype SNP identified as the target of selection, is proposed here as an explanatory mechanism for hypothesized failure to inactivate the channel at high Ca2+ concentrations in those who have the ancestral haplotype. This could result in an over-abundance of cellular Ca2+, which has been implicated in cancer, for those in settings where calcium dietary and supplemental intake is far higher than in their ancestral environment. This synthesis of recent research makes a case for investigation into the TRPV6 haplotype as a genomic factor in cancer disparity. If TRPV6 is found to be implicated, future research would be warranted to improve risk assessment and examine interventions with the aim of improving cancer outcomes for people of African descent. Citation Format: Patricia Francis-Lyon, Fahreen Malik, Xiaoyun Cheng, Alireza Ghezavati, Feihan Xin, Rafiki Cai. TRPV6 as a putative genomic susceptibility locus influencing racial disparities in cancer [abstract]. In: Proceedings of the Twelfth AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2019 Sep 20-23; San Francisco, CA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl_2):Abstract nr A069.