The androgen receptor CAG and GGN repeat polymorphisms and prostate cancer susceptibility in African-American men: results from the Flint Men’s Health Study

Abstract

Repeat lengths of the CAG and GGN microsatellites in exon 1 of the androgen receptor (AR) gene have been hypothesized to be associated with prostate cancer risk. In vitro studies have showed an inverse association between AR CAG and GGN repeat length and activity levels of the AR product. It is known that men of African descent have a higher incidence of and greater mortality from prostate cancer than men of Caucasian or Asian descent and, on average, a smaller number of repeats at AR CAG and GGN. Consistent with these findings, studies have also found increased AR protein expression levels in benign prostatic hyperplasia and prostatic diseased tissues from men of African descent. Despite these findings, limited studies have been conducted to evaluate the association between repeat lengths at AR CAG and prostate cancer risk in African Americans. Our study is the first such study to examine whether repeat length of the AR GGN repeat is associated with prostate cancer risk in African Americans. We found no evidence for an association between AR CAG or GGN repeat lengths and prostate cancer risk in a population-based sample of African Americans.

Prostate cancer in men of African origin

“…In a subsequent study of 319 veterans with prostate cancer, African-American men were again found to have shorter CAG repeat sequences than white men 44 . However, later epidemiological studies have failed to uncover a relationship between androgen receptor CAG repeats and prostate-cancer risk [45][46][47] ; in the Flint Men's Health Study, released in 2008, this lack of association even held true among African-American men 48 . Giovannucci 49 attributed the difference in study conclusions to the later studies being performed in the PSA era, noting that the earlier studies with positive findings largely consisted of younger men with more aggressive cancers.…”

Prostate cancer epidemiology in the United States

“…Researchers have looked at environmental differences such as differences in dietary and obesity patterns [26] and difference in obesity [27]. Others have looked at genetic differences among populations such as the number of CAG and CGN repeat polymorphism [28] or biochemical differences such as vitamin D deficiency [29]. These areas of investigation have been disappointing.…”

Persistent organic pollutants have dose and CAG repeat length dependent effects on androgen receptor activity in vitro

“…The glutamine stretch is encoded by a number of CAG bases in the AR gene, commonly referred to as the CAG repeat. The CAG number varies in length between individuals from approximately 10 to 30 repeats and displays population based diversity with African Americans having on average fewer CAG repeats than Caucasians and Far-Eastern Asians [20][21]. In Caucasian populations the median CAG repeat length is 22 amino acids [22][23], which recently was demonstrated to exhibit the highest transcriptional activity as compared to CAG repeat lengths in the outer normal ranges [24] .…”