Ecological model links proto-oncogene to high incidence of metastatic cancers in African-Americans Page: 37

                                
Journal of Cancer
Research & Therapy
Hilliard C, J Cancer Res Ther. 2018, 6(5):37-40
http://dx.doi.org/10.14312/2052-4994.2018-6

NobleResearch
An Open Access Publisher
www.nobleresearch.org

Hypothesis

Ecological model links proto-oncogene to high incidence of
metastatic cancers in African-Americans
Constance Hilliard, PhD',*
1 Department of History, University of North Texas, Denton, TX 76203, USA
Abstract
Cancers identified by the uncontrolled proliferation of the TRPV6 mRNA biomarker, kill African-Americans (AAs) at nearly twice the rate
of Whites. Malignancies assigned to this class include: Metastatic prostate cancer, triple negative breast cancer, colorectal and multiple
myeloma. This ecological model identifies the cause as an ethnic-specific haplotype of the TRPV6 calcium ion channel, which is also proto-
oncogenic. This ancestral TRPV6a variant has been shown in several studies to be more calcium absorbent than the non-African/European
TRPV6b allele. AAs inherited strong bones from their low-calcium consuming (200-400 mg/day) Niger-Kordofanian West African ancestors.
However, AAs are maladapted to the high calcium (1,000+ mg/day) food environment of the U.S. As a consequence, the ancestral TRPV6a
allele can become invasively oncogenic when over-exposed to excess free calcium ions, leading to the aforementioned class of cancers.

Keywords: ecological model; proto-oncogene; metastatic cancers; African-Americans

Hypothesis
The unusually high mortality rate of African-Americans
from an aggressive sub-type of cancers that are generally
fatal, is triggered by the Ca 2 hypersensitivity of the
ancestral TRPV6a proto-oncogene.
Introduction
Medical researchers have long noted that Americans of
African descent have a lower incidence than Whites for
such common malignancies as luminal A breast cancer
(Estrogen receptor-positive; HER2 receptor-negative),
Non-Hodgkin lymphoma and melanoma, while having
nearly twice the mortality rate for certain more aggressive
cancers. This ecological model identifies the underlying
reasons for this pattern of cancer susceptibility. In doing
so, it offers a therapeutic target for those cancers, which
at the present time, carry a low prognosis because of the
absence of targeted therapies for these tumor types [1].
The TRPV6a proto-oncogene
Metastatic prostate cancer (mPCa), triple negative breast
cancer, colorectal and multiple myeloma cancers present
different histologies and pathways. But, they are all
characterized by the upregulation of TRPV6 calcium ion
channel transcript and are generally incurable. The human
TRPV6 gene is a calcium ion channel, which plays a key role
in calcium homeostasis and mediates Ca 2 uptake in the
intestine. It is located on chromosome 7q33-q34 in close

proximity to the TRPV5 on 7q35. While nearly undetectable
in normal prostate, mammary and other tissues, it
becomes overexpressed in cancer tumorigenesis, initiating
cell growth, proliferation and metastases. In breast tissue,
TRPV6 mRNA expression is upregulated from 2 to 15
times the amount found in normal breast tissue. Recent
studies have found such a strong connection, that they
have suggested that the levels of TRPV6 mRNA be used as
a biomarker for metastatic prostate and colorectal cancer
[2]. In the case of multiple myeloma, a strong TRPV6
expression has been found in the bone marrow [3].
Studies have identified two functional variants for the
human TRPV6 gene. The African or ancestral TRPV6a
variant (accession number: AJ243500) has been shown to
be more calcium absorbent than the non-African TRPV6b
*Corresponding author: Constance Hilliard, Ph.D., Department of History,
University of North Texas, Denton, TX 76203, USA. Email: constance.
hilliard@unt.edu
Received 18 July 2018 Revised 22 August 2018 Accepted 27 August 2018
Published 3 September 2018
Citation: Hilliard C. Ecological model links proto-oncogene to high incidence
of metastatic cancers in African-Americans.J Cancer Res Ther. 2018; 6(5):37-
40. DOI: 10.14312/2052-4994.2018-6
Copyright: @ 2018 Hilliard C. Published by NobleResearch Publishers.
This is an open-access article distributed under the terms of the Creative
Commons Attribution License, which permits unrestricted use, distribution
and reproduction in any medium, provided the original author and source
are credited.

Open Access