Androgen receptor gene polymorphisms and risk of prostate cancer: a meta-analysis

Abstract

Although the association between CAG and GGN repeats in the androgen receptor gene and prostate cancer risk has been widely studied, it remains controversial from previous meta-analyses and narrative reviews. Therefore, we performed this meta-analysis to provide more precise estimates with sufficient power. A total of 51 publications with 61 studies for CAG repeats and 14 publications with 16 studies for GGN repeats were identified in the meta-analysis. The results showed that short CAG repeats (<22 repeats) carriers presented an elevated risk of prostate cancer than long CAG repeats (≥22) carriers (OR = 1.31, 95% CI 1.16 to 1.47). Prostate cancer cases presented an average fewer CAG repeats (MD = −0.85, 95% CI −1.28 to −0.42) than controls. Short GGN repeats (≤16) carriers presented an increased risk of prostate cancer than long GGN repeats (>16) carriers (OR = 1.38, 95% CI 1.05 to 1.82). In subgroup analyses, the abovementioned significant association was predominantly observed in Caucasian populations. The meta-analysis showed that short CAG and GGN repeats in androgen receptor gene were associated with increased risk of prostate cancer, especially in Caucasians.

BRCA2-Associated Prostate Cancer in a Patient With Spinal and Bulbar Muscular Atrophy

“…10-12 The length of AR gene polymorphic trinucleotide CAGs has been inversely correlated with the risk of developing prostate cancer, especially in whites. 11,13-15…”

Identification of Germline Genetic Variants that Increase Prostate Cancer Risk and Influence Development of Aggressive Disease

“…These approaches demonstrated modest success, although were frequently limited by factors including sample size constraints inherent to the available lower-throughput techniques of the era, population stratification, the genotyping only of specific founder mutations within a cohort rather than screening of full coding sequences of genes, and publication bias against the reporting of negative results. The CAG and GGN trinucleotide repeat polymorphisms within the transactivation domain of the androgen receptor gene are one example of an extensively studied candidate, however evidence for association between repeat length and PrCa risk has been inconsistent and modest [ 39 , 40 , 41 , 42 , 43 , 44 ]. Several other variants, genes or pathways were also examined under this approach, including the androgen [ 45 ] and oestrogen [ 46 ] metabolic pathways, and TP53 gene [ 47 ]; again with inconsistent evidence of association and magnitude or direction of effect frequently reported between studies.…”

Idiopathic Infertility as a Feature of Genome Instability

“…Genome instability in general and, more specifically, MSI is associated with increased cancer risk. Accordingly, short CAG and GGN repeats in the AR gene have been found to be correlated with a higher risk of prostate cancer, especially in Caucasian men [ 45 ].…”