The androgen receptor cytosine-adenine-guanine repeat length contributes to the development of epithelial ovarian cancer

Abstract

Ovarian cancer is the main cause of death among women with gynecological malignancies. Androgen and its receptors play an important role in ovarian cancer pathogenesis. Here, We aim to evaluate the relationship between AR CAG and GGN repeat length polymorphisms and Epithelial Ovarian Cancer (EOC) risk in a two-stage, case-control study among Chinese women. The repeat length was analyzed as a categorical variable for CAG_A and GGN_A (average allele), CAG-S and GGN_S (shorter allele), CAG-L and GGN_L (longer allele), respectively. The median value of the repeat length among the controls was used as the cutoff point. Women with longer AR CAG repeats had a decreased risk of developing EOC. The results was replicated in an independent samples. Compared to those with shorter (<22) CAG_A repeat length, women with longer (≥22) CAG_A repeats length had a 31% decreased EOC risk (OR = 0.69, 95% CI: 0.62–0.77, P = 5.06 × 10−11). For CAG_S and CAG_L, the results remain consistent. However, we didn't detected any significant associations for GGN_A, GGN_S, and GGN_L. This should be the first study to examine the association between AR repeat length polymorphisms and ovarian cancer risk in a relatively large group of Asian women.

Androgen receptor gene CAG repeat polymorphism and ovarian cancer risk: A meta-analysis

“…The abnormal range of CAG repeat length is usually associated with the risk of developing different cancer types including ovarian cancer (7)(8)(9)(10)(11). However, previous studies of the association between AR CAG repeat polymorphism and ovarian cancer risk have shown inconsistent results (10)(11)(12)(13)(14)(15)(16)(17). In this meta-analysis, we performed a comprehensive evaluation of the relationship between AR CAG repeat polymorphism and ovarian cancer risk under the allele, additive, dominant and recessive models.…”

“…Shorter CAG repeat length was associated with increased risk of HCC in men, but was associated with less susceptibility in women (36,37), suggesting different mechanisms are involved in the HCC development regarding men and women. The shorter CAG repeat length is associated with an increased risk of hyperandrogenic manifestations including hirsutism, annovulation, and acne in women and baldness and prostatic hyperplasia in men, perhaps because shorter length may facilitate chronic androgen stimulation which can result in enhanced proliferative activity (5,13). Compared to healthy women, patients with ovarian cancer have high levels of circulating androgen before the disease diagnosis, and ARs are usually detected in most ovarian cancer patients (38).…”

“…Ten of these publications were excluded according to the evaluation criteria: 6 publications were not case-control studies (20)(21)(22)(23)(24)(25), and another 4 did not provide detailed genotype or allele distribution data (26)(27)(28)(29). Finally, 8 case-control studies containing 6613 cases and 7041 controls were included in the current meta-analysis (10)(11)(12)(13)(14)(15)(16)(17). A flow chart of study selection process was shown in Figure 1, and the baseline characteristics of all included studies were presented in Table 1.…”

“…In exon 1 is a trinucleotide cytosine, adenine, guanine (CAG) repeat, which encodes a polyglutamine tract with varying lengths (5). It is reported that different ethnicities have different CAG repeat lengths, with the shortest being reported in African-Americans (mean,20; range, [10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29] and the longest in Mexican-Americans (mean,25; range, [16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32] (6). Studies have shown that CAG repeat lengths were associated with the risks of different cancer types in various populations, such as breast cancer, prostate cancer and colorectal cancer (7)(8)(9).…”

“…Studies have shown that CAG repeat lengths were associated with the risks of different cancer types in various populations, such as breast cancer, prostate cancer and colorectal cancer (7)(8)(9). In terms of ovarian cancer, some studies have shown that long CAG repeat allele was associated with increased ovarian cancer risk (10,11), while other studies have reported an inverse association between CAG repeat length and ovarian cancer risk (12,13). Furthermore, several studies suggested no relationship between CAG repeat length and ovarian cancer (14)(15)(16)(17).…”