Abstract 1211: Ecological model-generated hypothesis for high prostate cancer incidence in African-Americans: TRPV6a gene variant and calcium-ion hypersensitivity

Abstract

Abstract INTRODUCTION: This Ecological Model System (EMS) applies an evidence-based hypothesis to a health disparities conundrum posed by low-calcium-consuming African-American males in the sizable medical literature that attributes metastatic Prostate Cancer (PCa) for which this group is at high risk, to calcium over-consumption. This EMS identifies the ethnic-specific TRPV6 calcium ion channel,because of its unusually high calcium absorption capacity relative to the non-African variant, as the culprit. While it allowed the Niger-Kordofanian West African ancestors of black Americans to maintain strong bones on a 200 mg/ca/day diet, it is oncologically maladaptive for U.S. blacks. In America's high calcium, dairy food culture, the TRPV6a variant allows blacks, who are generally lactase non-persistent, to nevertheless absorb more of the mineral than whites and excrete less in their urine. These excess free calcium ions appear to initiate cell proliferation, leading to metastatic PCa, in which the TRPV6 gene becomes over-expressed. METHODS: To generate an algorithm-driven informative matrix, Medline and JSTOR searches were mined using keywords such as: metastatic prostatic cancer, androgen-castration-resistant, Niger-Kordofanian West Africans, TRPV6, TRPV5-renal excretion, TRPV6 over-expression biomarker. Secondary data sets from (1) “Prostate, Lung, Colorectal, Ovarian Cancer Screening Trial,” conducted between 1993 and 2001, 38,349 males (ages 55-74 years); (2) “California Collaborative Prostate Cancer Study”, a study of 4321 African-Americans and non-Hispanic Whites was analyzed using multivariable conditional logistic regression. RESULTS: This EMS reveals that at 400 mg/day/ca, metastatic PCa is observed in 17% of Blacks, but 0% of American Whites. 100% of the Black incidence is below 1150 mg/calcium intake, while 59% of White incidence from 1250-2000 mg. SUMMARY: Because the African TRPV6a calcium ion channel variant is more absorbent of free calcium ions than its non-African counterpart, this Ecological Model shows that carriers of this variant are at increased risk of metastatic PCa when exposed to high calcium food environments. CONCLUSION: Black hypersensitivity to calcium triggers metastatic PCa caused by high-calcium-absorbing African TRPV6a calcium ion channel variant. This EMS further hypothesizes that the high susceptibility of Blacks to other TRPV6-expressing cancers (e.g.triple negative breast cancer and colorectal cancer) share the same pathogenesis. This Model can be applied as well to generating hypotheses for STEM basic and translational research regarding Type II diabetes, hypertension, kidney disease. Citation Format: Constance B. Hilliard. Ecological model-generated hypothesis for high prostate cancer incidence in African-Americans: TRPV6a gene variant and calcium-ion hypersensitivity [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 1211.