Cancer Risk, Ethnicity & Race: Is It All in the Genes
Two recently published cancer studies reveal differences in the severity of cancer (specifically breast and colorectal) between black Americans and other racial or ethnic populations are based in genetic variations. I think we should pause a moment and recognize that today is National DNA Day, an observance popular in K-12 education to recognize the day that the research scientists at NIH completed sequencing of the human genome. The knowledge gained from that tremendous endeavor has informed physicians and scientists in countless labs since and the current findings in the disparities between the burden of illness suffered by blacks with breast or colorectal cancer tumors is no different.
Dr. Carol Rosenberg and her colleges at Boston University School of Medicine have discovered that cancer tumors lacking genetic expression for estrogen receptors, progesterone receptors and HER-2 (human epidermal growth factor), so called “triple-negative” tumors were more common among black women. Specifically, their study of 415 women (36% non-Hispanic white, 43% black, 10% Hispanic, and 10% other) revealed that black women have a three times greater risk of having triple-negative breast cancer tumors as compared to non-Hispanic whites. Triple-negative phenotype tumors (which make up 15% of all invasive breast cancers) have been associated with poor prognosis and low 5-year survival rates. The implications are significant to understanding the prevalence of an increased burden of illness and death suffered by black women developing breast cancer.
“The reasons explaining this finding are not certain, but it is possible that black women may be at intrinsically greater risk of these more aggressive tumors,” observed Dr. Rosenberg.
The proportion of black women suffering from triple-negative breast cancer tumors was the same when comparing women under or exactly fifty years of age to those over fifty, as well as women who were obese to those who we not obese. The findings of this study were release late last month in the Journal of Breast Cancer Research.
Earlier this month, Upender Manne, PhD and his colleges at University of Alabama at Birmingham released the results of their investigation of colorectal cancer in Clinical Cancer Research. Scientists have thoroughly documented he p53 gene and its association with colon cancer in the literature. In the current study, statistically significant differences in colorectal cancer tumors where identified and described. Dr. Manne and his team reviewed 373 patients (63% non-Hispanic white and 37% black surgically treated between 1985 and 1995 at the anatomical, cellular and genetic level. The codon 72 of the p53 protein can contain the amino acid (a protein building block) proline (Pro) or arginine (Arg). As a result, there are three different phenotypes of p53 protein Arg/Arg, Arg/Pro or Pro/Pro. In previous studies, researchers have found the Arg/Arg phenotype of the p53 protein to have a higher potential for inducing apoptosis (or programmed death of cancer cells). On the other hand, the Pro/Pro phenotype of the protein has been found to accompany a greater proliferation of cancer cells. In general, mutations that disrupted or inactivated the p53 protein have been associated with progression of the cancer.
The racial difference in the prevalence of these phenotypes of p53 protein associated with the colon cancer tumors was statistically significant. Nineteen (19%) percent of colorectal cancer tumors in blacks had the Arg/Arg phenotype protein compared to 36% of the tumors in whites; 64% of tumors in blacks had the Arg/Pro phenotype protein compared to 57% of the tumors in whites; and 17% of tumors in black had the Pro/Pro phenotype protein compared to 7% of whites. The implication of the numbers is this:
blacks had a higher prevalence of the p53 protein phenotype (Pro/Pro) which is associated with more aggressive tumors and progression of the cancer.
Specifically, this Pro/Pro phenotype was 2.5 times more likely to be associated with death in black patients than those with the other phenotypes. In stark contrast, these Pro/Pro phenotye p53 proteins were only 1.6 times more likely to be associated with death in white patients than those with the other phenotypes. As Dr. Manne stated,
“African-Americans, but not Caucasians, with the Pro/Pro phenotype had significantly higher mortality…and risk of death due to [colorectal cancer].”
This particular study, also identified additional, statistically significant
differences between tumors in blacks and non-Hispanic whites that create future opportunities to examine and disaggregate what Manne referred to as the “confounding from other lifestyle factors of the aggressiveness of the disease.”
Medscape Oncology contacted an independent physician, Dr. Hemant Roy of the Feinberg School of Medicine at Northwestern University to comment on the clinical significance of colorectal cancer study. “Risk assessment is complex, and this and other genetic polymorphisms are an important piece of the puzzle…While this observation may not necessarily represent a stand-alone future test, it takes us closer to understanding risk and hence targeting screening.” I think this observation speaks to the value of the molecular and genetic characterizations that come from health disparities research such as the two studies I discussed here, they decipher a piece of the entire puzzle that determine risk factors and help health care providers target and personalize the screening process.
Stead LA, Lash TL, Sobieraj JE, Chi DD, Westrup JL, Charlot M, Blanchard RA, Lee JC, King TC, Rosenberg CL. Triple-negative breast cancers are increased in black women regardless of age or body mass index. Breast Cancer Res. 2009 Mar 25;11(2):R18.
Beals JK. New Polymorphisms Affect Colorectal Cancer Risk, Progression in
Blacks. In Medscape Medical News. Cited April 24, 2009. Available at <http://www.medscape.com/viewarticle/590604>
Katkoori VR, Jia X, Shanmugam C, Wan W, Meleth S, Bumpers H, Grizzle WE, Manne U. Prognostic significance of p53 codon 72 polymorphism differs with race in colorectal adenocarcinoma. Clin Cancer Res. 2009 Apr 1;15(7):2406-16.