Abstract 3335: Innovative mathematical model links TRPV6 genotype to high triple negative breast cancer mortality rate in African-American females

Abstract

Abstract INTRODUCTION: The mortality rate for African-American (AA) females is 4 times that of Whites due to the former’s higher susceptibility to Triple Negative Breast Cancer (TNBC). This study suggests that the African/ancestral TRPV6 calcium ion channel may be more calcium-absorbent than the European/derived TRPV6 variant. The 800 mg. daily calcium intake of AA women is twice that of their low-osteoporotic Niger-Kordofanian ancestors. This maladaptation may expose AA females’ mammary tissue to free calcium ions in excess of biological need. Ca2+ flooding appears to trigger over-expression of TRPV6 transcript, which becomes a biomarker for estrogen receptor (ER)-negative breast tumors. Therefore, this study introduces a Genetic-Population Specific Mathematical Model (GPs Mathematical Model), which identifies the ancestral TRPV6 calcium ion channel in AA females as a novel therapeutic target for TNBC and suggests TNBC-avoidant dietary guidelines for this ethnic population. . METHODS: The GPs Mathematical Model correlates ratios of DNA ancestry and calcium intake levels per genetic population. An interactive map based on data from 74 countries provided global calcium intake. Retrospective data sets on the genetic ancestry of 5,269 self-described African Americans, 8,663 Latinos, and 148,789 European Americans were correlated to the 1000 Genomes Project data. RESULTS: This Model identifies a normal range of dietary calcium consumption for AAs. The admixture ratio of this population is on average, 0.74 Niger-Kordofanian DNA; 0.24 Northern European DNA; 0.01 Native American DNA. Nutritional studies indicate that the average daily calcium intake for healthy Niger-Kordofanians, Northern Europeans and Native Americans are 200 to 400 mg, 1000 to 1200 mg, and 1100 mg. respectively or 0.75 (NK DNA Ancestry (200,400) + 0.24 NE DNA Ancestry (1000, 1200) + 0.01 NA DNA Ancestry(1100) = a range from 401 to 599, averaged to 500 mg/calcium/day. This Model shows that the calcium intake of AA females is 160% to 240% higher than the theoretical value derived from this ethnic group’s genetic ancestry. SUMMARY: This Genetic Population-Specific Mathematical Model suggests that the higher calcium intake of AA females relative to their genetic ancestors may create hyper-reactivity of ancestral TRPV6 leading to TNBC. CONCLUSION: Dietary calcium intake in excess of biological needs may trigger AA females’ high susceptibility to “TRPV6-expressing” Triple Negative Breast Cancer. The Genetic Population-Specific Mathematical Model provides an AA set-point of 500mg/d for dietary calcium intake, which is 0.375 lower than this ethnic population’s average consumption of 800 mg/calcium/day. The use of TRPV6 inhibitors should be tried in order to control the disease. In addition, a reduction in dietary calcium may have a prophylactic effect on this population's high susceptibility to TNBC. Note: This abstract was not presented at the meeting. Citation Format: Constance B. Hilliard. Innovative mathematical model links TRPV6 genotype to high triple negative breast cancer mortality rate in African-American females [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 3335.