Androgen Receptor CAG Repeat Research Articles

152 Correlation Between Androgen Receptor Cag Repeat Length Polymorphism and Metabolic Syndrome, Late Onset Hypogonadism in Korean Male

152 Correlation Between Androgen Receptor Cag Repeat Length Polymorphism and Metabolic Syndrome, Late Onset Hypogonadism in Korean Male

Combined effect of polymorphisms in type III 5-α reductase and androgen receptor gene with the risk of benign prostatic hyperplasia in Korea

We evaluated whether type III 5-alpha reductase (SRD5A3; steroid reductase 5-alpha 3) polymorphism was associated with susceptibility of benign prostate hyperplasia (BPH) and the combined effects in BPH risk between the type of short tandem repeat (STR) in SRD5A3 and the length of trinucleotide (CAG) repeats in androgen receptor (AR) gene. We compared the length of AC repeats in STR region of SRD5A3 gene and a CAG repeat in AR in 188 BPH patients who underwent transurethral resection of prostate (TURP) and 98 controls by polymerase chain reaction-based methods. We defined short type was less than 21 copies of AC repeats. The odds ratio for BPH between the men with at least one of short type and with both large types of STR in SRD5A3 gene was 3.10 (95% confidence interval [CI], 1.87–5.16; P=0.000). And BPH was 2.35 times more likely to occur in with less than 23 copies of CAG repeats than men equal or greater than 23 copies in AR gene (95% CI, 1.18–2.36; P=0.016). The men with the large type of STR and ≥23 copies of CAG repeats have 5.3 times BPH risk compared to the reference group with the at least one of the short type of STR and <23 copies (P<0.000). In conclusion, these results suggest that shorter AC repeats of SRD5A3 gene and shorter CAG repeats of AR gene were associated with an increased risk for BPH. However, the interaction between above two factors was not affected in risk of BPH.

The role of testosterone in coordinating male life history strategies: The moderating effects of the androgen receptor CAG repeat polymorphism

Partnered fathers often have lower testosterone than single non-parents, which is theorized to relate to elevated testosterone (T) facilitating competitive behaviors and lower T contributing to nurturing. Cultural- and individual-factors moderate the expression of such psychobiological profiles. Less is known about genetic variation's role in individual psychobiological responses to partnering and fathering, particularly as related to T. We examined the exon 1 CAG (polyglutamine) repeat (CAGn) within the androgen receptor (AR) gene. AR CAGn shapes T's effects after it binds to AR by affecting AR transcriptional activity. Thus, this polymorphism is a strong candidate to influence individual-level profiles of “androgenicity.” While males with a highly androgenic profile are expected to engage in a more competitive-oriented life history strategy, low androgenic men are at increased risk of depression, which could lead to similar outcomes for certain familial dynamics, such as marriage stability and parenting. Here, in a large longitudinal study of Filipino men (n=683), we found that men who had high androgenicity (elevated T and shorter CAGn) or low androgenicity (lower T and longer CAGn) showed elevated likelihood of relationship instability over the 4.5-year study period and were also more likely be relatively uninvolved with childcare as fathers. We did not find that CAGn moderated men's T responses to the fatherhood transition. In total, our results provide evidence for invested fathering and relationship stability at intermediate levels of androgenicity and help inform our understanding of variation in male reproductive strategies and the individual hormonal and genetic differences that underlie it.

Contributions of CAG repeat length in the androgen receptor gene and androgen profiles to premature pubarche in Korean girls.

The CAG repeat length of the androgen receptor (AR) gene, which exhibits an inverse relationship to AR sensitivity, might influence the development of the pubarche along with hyperandrogenemia. There are ethnic differences in the AR CAG repeat length, however, no Asian studies on premature pubarche (PP) have been reported, including Korea. Our objectives were to examine the hormone levels and AR CAG repeat length, and to assess their contributions to PP in Korean girls. Subjects with PP (n=16) and normal pubarche (NP, n=16), and normal controls (NC, n=16) were enrolled. The levels of dehydroepiandrosterone (DHEA), dehydroepiandrosterone-sulfate (DHEAS), 17-hydroxyprogesterone (17-OHP), and free testosterone (FT) were checked. The methylation-weighted (MW) average CAG repeat lengths were analyzed. The median ages at pubarche were 7.4 and 8.9 years in the PP and NP groups, respectively, and the levels of 17-OHP, DHEAS, and FT were similar in both groups. The PP group exhibited a higher DHEAS:DHEA ratio than the NP group (P=0.014). The medians of the MW average CAG repeat length of the AR gene were 22.4 for all subjects and did not differ among the PP (22.3), NP (22.4), and NC (22.2) groups. The AR CAG repeat lengths in the PP and NP groups did not correlate with DHEAS or FT levels. These results suggest that the AR CAG repeat length was not involved in the development of PP in Korean girls. However, excessive adrenal androgen levels, particularly those caused by increased sulfotransferase activity, might be important in the pathogenesis of PP.

The androgen receptor gene CAG repeat in relation to 4-year changes in androgen-sensitive endpoints in community-dwelling older European men.

The androgen receptor (AR) gene exon 1 CAG repeat length has been proposed to be a determinant of between-individual variations in androgen action in target tissues, which might regulate phenotypic differences of human ageing. However, findings on its phenotypic effects are inconclusive. To assess whether the AR CAG repeat length is associated with longitudinal changes in endpoints that are influenced by testosterone (T) levels in middle-aged and elderly European men. Multinational European observational prospective cohort study. A total of 1887 men (mean ± s.d. age: 63 ± 11 years; median follow up: 4.3 years) from centres of eight European countries comprised the analysis sample after exclusion of those with diagnosed diseases of the hypothalamic-pituitary-testicular (HPT) axis. Longitudinal associations between the AR CAG repeat and changes in androgen-sensitive endpoints (ASEs) and medical conditions were assessed using regression analysis adjusting for age and centre. The AR CAG repeat length was treated as both a continuous and a categorical (6-20; 21-23; 24-39 repeats) predictor. Additional analysis investigated whether results were independent of baseline T or oestradiol (E2) levels. The AR CAG repeat, when used as a continuous or a categorical predictor, was not associated with longitudinal changes in ASEs or medical conditions after adjustments. These results were independent of T and E2 levels. Within a 4-year time frame, variations in the AR CAG repeat do not contribute to the rate of phenotypic ageing, over and above, which might be associated with the age-related decline in T levels.

Androgen receptor CAG and GGN repeat length variation contributes more to the tumorigenesis of osteosarcoma.

The androgen receptor (AR) is involved in the differentiation and growth of many cancers. We hypothesized that two microsatellite polymorphic variants, AR (CAG)n and (GGN)n repeats, were also associated with the development of Papillary thyroid cancer (PTC) and Osteosarcoma. In current study, we conducted two case-control studies in a Chinese population to investigate the possible relationship between these two AR repeat polymorphisms and the risk of PTC and Osteosarcoma. The AR CAG repeat length was significantly associated with both risk of PTC and Osteosarcoma. Subjects with shorter AR CAG repeats had a higher risk of developing PTC (OR = 1.47, 95% CI: 1.17–1.85, P = 0.001) and Osteosarcoma (OR = 1.53, 95% CI: 1.19–1.97, P = 9.2 × 10–4). Specifically, shorter GGN repeats also contribute a significant increased risk of Osteosarcoma (OR = 1.35, 95% CI: 1.03–1.77, P = 0.030). Our results contribute to a better understanding of the complex hormone related mechanisms underlying PTC and Osteosarcoma.

Effects of 8-Year Treatment of Long-Acting Testosterone Undecanoate on Metabolic Parameters, Urinary Symptoms, Bone Mineral Density, and Sexual Function in Men With Late-Onset Hypogonadism

IntroductionThe long-term effects of long-acting testosterone undecanoate (TU) and androgen receptor CAG repeat lengths in Thai men with late-onset hypogonadism (LOH) have not been reported. AimTo analyze the 8-year follow-up effects of intramuscular TU therapy on metabolic parameters, urinary symptoms, bone mineral density, and sexual function and investigate CAG repeat lengths in men with LOH. MethodsWe reviewed the medical records of 428 men with LOH who had been treated with TU and 5 patients were diagnosed with prostate cancer during TU therapy. There were 120 patients (mean age = 65.6 ± 8.9 years) who had 5 to 8 years of continuous TU supplementation and sufficiently completed records for analysis. Genomic DNA was extracted from peripheral blood and the CAG repeat region was amplified by polymerase chain reaction. Fragment analysis, sequencing, electropherography, and chromatography were performed. Main Outcome MeasuresThe main outcome measure was dynamic parameter changes during testosterone supplementation. ResultsTU did not improve all obesity parameters. A statistically significant decrease was found in waist circumference, percentage of body fat, glycated hemoglobin, cholesterol, low-density lipoprotein, and International Prostate Symptom Score (P < .05). TU did not produce differences in body mass index, high-density lipoprotein, triglyceride, or the Aging Male Symptoms score from baseline. However, a statistically significant increase was found in the level of testosterone, prostate-specific antigen, hematocrit, International Index of Erectile Function score, and vertebral and femoral bone mineral density (P < .05). No major adverse cardiovascular events or prostate cancer occurred during this study. The CAG repeat length was 14 to 28 and the median CAG length was 22. There was no association between CAG repeat length and any of the anthropometric measurements. ConclusionLong-term TU treatment in men with LOH for up to 8 years appears to be safe, tolerable, and effective in correcting obesity parameters.

Androgen receptor CAG repeat polymorphism and hypothalamic‐pituitary‐gonadal function in Filipino young adult males

Testosterone (T), the primary androgenic hormone in males, is stimulated through pulsatile secretion of LH and regulated through negative feedback inhibition at the hypothalamus and pituitary. The hypothalamic-pituitary-gonadal (HPG) axis also controls sperm production through the secretion of follicle-stimulating hormone (FSH). Negative feedback in the HPG axis is achieved in part through the binding of T to the androgen receptor (AR), which contains a highly variable trinucleotide repeat polymorphism (AR-CAGn). The number of repeats in the AR-CAGn inversely correlates with transcriptional activity of the AR. Thus, we predicted longer AR-CAGn to be associated with higher T, LH, and FSH levels. We examined the relationship between AR-CAGn and total plasma T, LH, and FSH, as well as "bioavailable" morning (AM-T) and evening (PM-T) testosterone in 722 young (21.5 ± 0.5 years) Filipino males. There was no relationship between AR-CAGn and total T, AM-T, or LH (P > .25 for all). We did observe a marginally non-significant (P = .066) correlation between AR-CAGn and PM-T in the predicted direction, and a negative correlation between AR-CAGn and FSH (P = .005). Our results both support and differ from previous findings in this area, and study parameters that differ between our study and others, such as participant age, sample time, and the role of other hormones should be considered when interpreting our findings. While our data point to a modest effect of AR-CAGn on HPG regulation at best, the AR-CAGn may still affect somatic traits by regulating androgenic activity at peripheral tissues.

Positive association of the androgen receptor CAG repeat length polymorphism with the risk of prostate cancer.

Prostate cancer (PC) is the most frequently diagnosed cancer in Ecuador (15.6%). The androgen receptor gene codes for a protein that has an androgen‑binding domain, DNA‑binding domain and N‑terminal domain, which contains two polymorphic trinucleotide repeats (CAG and GGC). The aim of the present study was to determine whether variations in the number of repetitions of CAG and GGC are associated with the pathological features and the risk of developing PC. The polymorphic CAG and GGC repeat lengths in 108mestizo patients with PC, 148 healthy mestizo individuals, and 78 healthy indigenous individuals were examined via a retrospective case‑control study. Genotypes were determined by genomic sequencing. The results demonstrated that patients with ≤21 CAG repeats have an increased risk of developing PC [odds ratio (OR)=2.99, 95% confidence interval (CI) =1.79‑5.01; P<0.001]. The presence of ≤21 CAG repeats was also associated with a tumor stage ≥T2c (OR=4.75; 95% CI=1.77‑12.72; P<0.005) and a Gleason score ≥7 (OR=2.9; 95% CI=1.1‑7.66; P=0.03). In addition, the combination of ≤21 CAG and ≥17 GGC repeats was associated with the risk of developing PC (OR=2.42; 95% CI=1.38‑4.25; P=0.002) and with tumor stage ≥T2c (OR=2.77; 95% CI=1.13‑6.79; P=0.02). In conclusion, the histopathological characteristics and PC risk in Ecuadorian indigenous and mestizo populations differs in association with the CAG repeats, and the combination of CAG and GGC repeats.

Weakness and Progressive Muscle Tightness Diagnosed as Kennedy Disease

Kennedy disease is a rare X-linked neurodegenerative disorder that affects patients in 30-50 years of age. It is caused by CAG-repeat in androgen receptor gen. There is no known effective treatment for Kennedy disease. We report a 60-year-old man who had fasciculations and proximal and distal muscle weakness. Physical examination showed involvement of the bulbar musculature accompanied by tongue atrophy and perioral muscle weakness. Furthermore, he had bilateral gynecomastia. Laboratory and imaging findings were normal, except electromyography that showed chronic proximal and distal denervation. Finally, the patient diagnosed with Kennedy disease according to clinical presentation and EMG abnormality that confirmed with genetic study.

076 Correlation between Androgen Receptor CAG Repeat Length Polymorphism and Metabolic Syndrome, Late Onset Hypogonadism in Korean Male

076 Correlation between Androgen Receptor CAG Repeat Length Polymorphism and Metabolic Syndrome, Late Onset Hypogonadism in Korean Male

AB080. Correlation between androgen receptor CAG repeat length polymorphism and metabolic syndrome, late onset hypogonadism in Korean male

ObjectiveIt is generally assumed that there is a negative linear association between androgen receptor (AR) sensitivity and the CAG repeat length. However, correlation between CAG repeat length and clinical factors of metabolic syndrome (MS), late onset hypogonadism is unclear. In this study we explored the relationship between AR CAG repeat length polymorphism and MS, late onset hypogonadism (LOH) in a Korean male population.MethodsThe association between AR CAG repeat length polymorphism and MS was analyzed in 241 Korean men (20–90 years old). MS was diagnosed according to the NCEP criteria (any three or more of the following components were present: abdominal obesity [waist circumference (WC) >102 cm], triglycerides >150 mg/dL, HDL cholesterol <40 mg/dL, fasting glucose >110 mg/dL, or blood pressure of >130/85 mmHg). LOH was diagnosed by serum testosterone level of <3.5 ng/mL and androgen deficiency in the aging male questionnaire positive. AR CAG repeat length polymorphism was determined by microsatellite fragment sizing and association with clinical factors and questionnaire related with LOH [patient health questionnaire-9 (PHQ), aging male symptom scale (AMS), and international index of erectile function (IIEF)] were analyzed.ResultsMean age of the patients was 56.9±11.2 years. Mean AR CAG repeat length and serum testosterone levels were 26.7±8.9 and 5.6±2.3 ng/mL, respectively. A Total of 64 men (26.6%) were diagnosed with MS and 22 men were diagnosed with LOH. Men with MS showed no significant difference in AR CAG repeat length compared with men without MS (P=0.325). AR CAG repeat length was not associated with HDL, LDL, triglyceride (P=0.397, P=0.609, P=0.867), but showed significant association with HbA1c (r=0.103, P=0.029). Men with LOH showed no significant difference in AR CAG repeat length compared with men without LOH (P=0.665). However as CAG repeat length was increased, AMS and PHQ scores were decreased and IIEF score was increased, significantly (r=−0.118, r=−0.153, r=0.069) (P<0.01, P<0.01, P<0.01).ConclusionsIn conclusion, AR CAG repeat length seems to be associated with HbA1c and clinical symptoms of LOH in Korean male.

Analysis of the androgen receptor CAG repeats length in Iranian patients with idiopathic non-obstructive azoospermia

Abstract Objective The present study was performed to determine whether expansion of the CAG repeat in exon 1 of the AR gene is correlated with non-obstructive azoospermia (NOA) in Iranian infertile men. Methods The CAG repeat length was investigated in 307 Iranian men, 104 infertile men with NOA and 203 fertile controls using primers flanking the CAG repeat region in exon 1 of the AR gene. Results The most common allele in the patients and controls was 23 (18.39%) and 21 (19.70%) CAG repeats with the mean number of 21.97 ± 2.772 and 21.10 ± 2.674, respectively (P = 0.013). Conclusion Although our results indicate a significant negative correlation between the length of CAG repeat and male infertility, however, other genetic modifiers may be required in order to cause male infertility.

Androgen receptor gene polymorphism influence fat accumulation: A longitudinal study from adolescence to adult age.

To determine the influence of androgen receptor CAG and GGN repeat polymorphisms on fat mass and maximal fat oxidation (MFO), CAG and GGN repeat lengths were measured in 128 young boys, from which longitudinal data were obtained in 45 of them [mean ± SD: 12.8 ± 3.6 years old at recruitment, and 27.0 ± 4.8 years old at adult age]. Subjects were grouped as CAG short (CAGS ) if harboring repeat lengths ≤ 21, the rest as CAG long (CAGL ); and GGN short (GGNS ) if GGN repeat lengths ≤ 23, or long if > 23 (GGNL ). CAGS and GGNS were associated with lower adiposity than CAGL or GGNL (P < 0.05). There was an association between the logarithm of CAG repeats polymorphism and the changes of body mass (r = 0.34, P = 0.03). At adult age, CAGS men showed lower accumulation of total body and trunk fat mass, and lower resting metabolic rate (RMR) and MFO per kg of total lean mass compared with CAGL (P < 0.05). GGNS men also showed lower percentage of body fat (P < 0.05). In summary, androgen receptor CAG and GGN repeat polymorphisms are associated with RMR, MFO, fat mass, and its regional distribution in healthy male adolescents, influencing fat accumulation from adolescence to adult age.

Androgen receptor CAG and GGN repeat polymorphisms influence performance in boys and girls.

Shorter CAG and GGN androgen receptor (AR) repeat polymorphisms are associated with stronger androgen signaling, and therefore, could influence lean mass and exercise performance during growth. Physical fitness and body composition were measured by standardized procedures and the length of CAG and GGN repeats was determined by PCR and fragment analysis in 152 boys (11.5±2.6 years; Tanner ≤5) and 116 girls (10.1±3.2 years; Tanner ≤5). Individuals were grouped as CAG short (CAGS) if harboring repeat lengths of ≤21 and CAG long (CAGL) if CAG >21. Moreover, subjects were grouped as GGN short (GGNS) if harboring repeat lengths of ≤23 and GGN long (GGNL) if GGN>23. No significant differences in anthropometrics and body composition were observed between either CAGS and CAGL groups and GGNS and GGNL groups. Boys harboring CAGS completed the 300-meter test faster than their CAGL counterparts. Moreover, girls from the GGNL group showed a significant higher VO2max than those in the GGNS group. In summary, carrying a short allele of the androgen receptor CAG repeat polymorphism is associated to higher anaerobic performance in boys, whereas long alleles of androgen receptor GGN polymorphisms are associated to higher aerobic capacity in girls.

Androgen receptor CAG repeat length and estrogen receptor status in postmenopausal breast cancer prognosis.

The influence of the androgen receptor (AR) CAG repeat polymorphism on breast cancer is controversial. We investigated the combined effects of CAG repeat length and estrogen receptor (ER) status on prognosis in 355 postmenopausal women with primary breast cancer. CAG repeat length was determined by the HUMARA test. Relapse-free survival (RFS) and overall survival (OS) according to the X-weighted CAG repeat biallelic mean (XWBM) were investigated by univariate and multivariate analysis. XWBM was not associated with RFS or OS, but a significant interaction between XWBM and ER status (p = 0.002) was found for OS. ER-negative patients with median XWBM &lt;20 showed lower OS than ER-negative/XWBM ≥20 patients (HR = 0.270; 95% Cl: 0.073-0.999). ER-negative/XWBM &lt;20 patients also had significantly lower OS than ER-positive women, irrespective of CAG repeat length (p&lt;0.001). Accordingly, estimated OS was lowest in ER-negative patients with XWBM &lt;20 (OS: 0.63, 95% CI: 0.41-0.79) and highest in ER-positive patients with XWBM &lt;20 (OS: 0.95, 95% CI: 0.90-0.97). Our data suggest that short CAG repeat length is associated with increased risk of death in ER-negative disease but is related to better survival when ER is expressed. These findings are in agreement with the hypothesis that AR may stimulate or inhibit breast cancer growth depending on ER status, AR transactivation, and the endocrine-metabolic environment of breast tumors. Evaluation of CAG repeat length together with ER status could help improve the estimation of the risk of death, with possible implications for the optimization of standard breast cancer treatment and implementation of prevention strategies.

Association of androgen receptor CAG repeat polymorphism and risk of epithelial ovarian cancer

Biological and epidemiologic evidence suggested that androgen and its receptor may play an important role in ovarian carcinogenesis. However, results of previous association studies about ovarian cancer and AR CAG repeat polymorphism were inconsistent. Furthermore, none of these studies were conducted in Asians. We evaluated the relationship between AR CAG repeat length and epithelial ovarian cancer (EOC) risk among a Chinese population including 1800 pathologically confirmed EOC patients and 1800 frequency matched controls. Women with longer AR CAG repeats had a decreased EOC risk (OR=0.87 for per CAG_A increase, 95% CI: 0.81-0.95). Compared to those with shorter (<22) CAG_A repeat length, women with of longer (≥22) CAG_A repeats had a 34% decreased EOC risk (OR=0.66, 95% CI: 0.57-0.75). For CAG_S and CAG_L, the results remained consistent. Our findings suggest that androgen signaling contributes to the development of ovarian cancer.

Size matters: Associations between the androgen receptor CAG repeat length and the intrafollicular hormone milieu

Granulosa cell (GC) expressed androgen receptors (AR) and intrafollicular androgens are central to fertility. The transactivating domain of the AR contains a polymorphic CAG repeat sequence, which is linked to the transcriptional activity of AR and may influence the GC function. This study aims to evaluate the effects of the AR CAG repeat length on the intrafollicular hormone profiles, and the gene expression profiles of GC from human small antral follicles.In total, 190 small antral follicles (3–11 mm in diameter) were collected from 58 women undergoing ovarian cryopreservation for fertility preservation. The biallelic mean of the CAG repeat lengths were calculated for each woman, and grouped in three groups: Long CAG repeats (23–26 mean CAG); medium CAG repeats (20.5–22.5 mean CAG) and short CAG repeats (17.5–20.0 mean CAG). The following parameters were measured: follicle diameter, intrafollicular levels of Anti-Müllerian Hormone (AMH), progesterone, oestradiol, testosterone and androstenedione, and GC gene expression levels of FSHR, LHR, AR, CYP19A1, and AMH.The long CAG repeat lengths were associated with significantly decreased testosterone levels, as compared to medium CAG repeats (P = 0.05) and short CAG repeats (P = 0.003). Furthermore, in follicles 3–6 mm in diameter, the long CAG repeats were associated with significantly increased LHR and CYP19A1 gene expression levels compared to short CAG repeat lengths (P = 0.004 and P = 0.04 respectively), and significantly increased LHR expression compared to medium CAG repeat lengths (P = 0.03).In conclusion, long CAG repeat lengths in the AR were associated to significant attenuated levels of androgens and an increased conversion of testosterone into oestradiol, in human small antral follicles.

Androgen Receptor Gene Polymorphism, Aggression, and Reproduction in Tanzanian Foragers and Pastoralists.

The androgen receptor (AR) gene polymorphism in humans is linked to aggression and may also be linked to reproduction. Here we report associations between AR gene polymorphism and aggression and reproduction in two small-scale societies in northern Tanzania (Africa)—the Hadza (monogamous foragers) and the Datoga (polygynous pastoralists). We secured self-reports of aggression and assessed genetic polymorphism of the number of CAG repeats for the AR gene for 210 Hadza men and 229 Datoga men (aged 17–70 years). We conducted structural equation modeling to identify links between AR gene polymorphism, aggression, and number of children born, and included age and ethnicity as covariates. Fewer AR CAG repeats predicted greater aggression, and Datoga men reported more aggression than did Hadza men. In addition, aggression mediated the identified negative relationship between CAG repeats and number of children born.

CAG repeat polymorphisms in the androgen receptor and breast cancer risk in women: a meta-analysis of 17 studies.

The association between polymorphic CAG repeats in the androgen receptor gene in women and breast cancer susceptibility has been studied extensively. However, the conclusions regarding this relationship remain conflicting. The purpose of this meta-analysis was to identify whether androgen receptor CAG repeat lengths were related to breast cancer susceptibility. The MEDLINE, PubMed, and EMBASE databases were searched through to December 2014 to identify eligible studies. Data and study quality were rigorously assessed by two investigators according to the Newcastle-Ottawa Quality Assessment Scale. The publication bias was assessed by the Begg’s test. Seventeen eligible studies were included in this meta-analysis. The overall analysis suggested no association between CAG polymorphisms and breast cancer risk (odds ratio [OR] 1.031, 95% confidence interval [CI] 0.855–1.245). However, in the subgroup analysis, we observed that long CAG repeats significantly increased the risk of breast cancer in the Caucasian population (OR 1.447, 95% CI 1.089–1.992). Additionally, the risk was significantly increased in Caucasian women carrying two alleles with CAG repeats ≥22 units compared with those with two shorter alleles (OR 1.315, 95% CI 1.014–1.707). These findings suggest that long CAG repeats increase the risk of breast cancer in Caucasian women. However, larger scale case-control studies are needed to validate our results.