Abstract B069: Ecological model links proto-oncogene to high susceptibility of Blacks to TRPV6-expressing metastatic cancers

Introduction: This ecological model traces the etiology of a certain class of metastatic cancers, which kills Blacks at more than twice the rate of Whites. These malignancies, defined by the uncontrolled proliferation of TRPV6 mRNA in mutagenic tissue, include metastatic prostate cancer, triple-negative breast cancer, and colorectal and ovarian cancer. This study will show that the cause is an ethnic-specific haplotype of the TRPV6 calcium ion channel. This proto-oncogenic African TRPV6a variant is more calcium absorbent than the non-African/European TRPV6b allele. African-Americans inherited strong bones from their low-calcium-consuming (200-400 mg/day) Niger-Kordofanian West African ancestors. However, American Blacks are maladapted to the high-calcium food environment of the U.S. This research shows that the ancestral TRPV6a allele can become invasively oncogenic when overexposed to free calcium ions, leading to the aforementioned class of cancers.

Methods: Analyses of the incidence of TRPV6-expressing cancers in Blacks and Whites as a function of dietary consumption are conducted.

Results: These data show a direct correlation between levels of calcium intake in Blacks, who carry the ancestral TRPV6a calcium ion channel, and incidence of the following hormonal cancers: metastatic prostate cancer, triple-negative breast cancer, colorectal cancer and ovarian cancer.

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 prostate cancer, triple-negative breast cancer, and ovarian and colorectal cancers, when exposed to high-calcium food environments.

Conclusions: Hypersensitivity to Ca2+ triggers certain metastatic cancers in Blacks, characterized by the upregulation of TRPV6 transcript. Lidocaine and SOR-C-13, a peptide derived from the saliva of the short-tail shrew, are identified as potential TRPV6 calcium channel inhibitors.

Citation Format: Constance B. Hilliard. Ecological model links proto-oncogene to high susceptibility of Blacks to TRPV6-expressing metastatic cancers [abstract]. In: Proceedings of the Eleventh AACR Conference on the Science of Cancer Health Disparities in Racial/Ethnic Minorities and the Medically Underserved; 2018 Nov 2-5; New Orleans, LA. Philadelphia (PA): AACR; Cancer Epidemiol Biomarkers Prev 2020;29(6 Suppl):Abstract nr B069.