Genetic polymorphisms and haplotype of hormone-related genes are associated with the risk of breast cancer in Chinese women

Abstract

ABSTRACT. Sex hormones play important roles in breast cancer (BC) development. This study investigated associations between BC risk and hormone-related gene variants in Chinese women. In a cohort of 336 patients with histopathologically confirmed BC and 390 age-matched controls, we genotyped seven single nucleotide polymorphisms (SNPs) in five hormone-related genes: estrogen receptor-α (ESR1), aromatase (CYP19), catechol-O-methyl transferase (COMT), sex hormonebinding globulin (SHBG), and glutathione S-transferase (GSTP1). Among these seven SNPs, the SNPs in GSTP1 rs1695 [A/G; odds ratio (OR): 1.68; 95% confidence interval (CI): 1.23-2.30] and ESR1 rs2046210 (C/T; OR: 1.39; 95%CI = 1.02-1.91) were associated with an increased risk among heterozygote carriers. Homozygotes of minor alleles of CYP19 rs10046 (CC) were associated with a reduced risk of BC with OR: 0.61 (95%CI = 0.39-0.95). In addition, a stratified analysis by menopausal status indicated that the association of the CYP19 polymorphisms (rs10046 and rs700519) with BC risk was mainly evident in premenopausal women, and the association of CYP19 rs700519 with BC risk was significant in women less than 50 years old. Haplotype analysis identified 15 common haplotypes (>1%). The haplotype TGGGGTC was significantly associated with BC risk compared with the reference haplotype CGAGGTC (OR > 1000, P < 0.0001). Our data demonstrate that these ESR1, GSTP1, and CYP19 polymorphisms are associated with risk of BC, and the risk haplotype TGGGGTC could help to identify populations with high susceptibility to BC in Chinese women.

Intake of total cruciferous vegetable and its contents of glucosinolates and isothiocyanates, glutathione S-transferases polymorphisms and breast cancer risk: a case–control study in China

“…Previous studies suggested that the functional mutation of the GSTP1 rs1695 polymorphisms may reduce the activity of GST-π enzyme deactivating and detoxifying carcinogens and thus may increase cancer vulnerability (40) . Nevertheless, our data showed no significant association between the GSTP1 homozygous mutant GG genotype and breast cancer risk, which was consistent with a 2016 meta-analysis of thirty-six case-control studies including 20 615 cases and 20 481 controls (19) , and studies from China (39) and Cyprus (41) , but contrary to studies from Shanghai (23) and Zhejiang (38) of China which found that the GSTP1 GG genotype was significantly associated with greater risk of breast cancer (OR 2•23 and 1•50, respectively, GG v. AA). The GSTM1 and GSTT1 null genotypes were prevalent among 60•7 and 16•3 % of controls in the present study, which was consistent with the rate of GSTM1 null genotype (59•1 %), but much lower than that of GSTT1 null genotype (51•9 %) in Shanghai Women's Health Study (42) .…”

“…The frequency of GSTP1 G allele was 18•1 % among controls in the present study. It was in accordance with the reported frequency of GSTP1 G allele from three studies in China (23,38,39) . Previous studies suggested that the functional mutation of the GSTP1 rs1695 polymorphisms may reduce the activity of GST-π enzyme deactivating and detoxifying carcinogens and thus may increase cancer vulnerability (40) .…”

“…The time-concordant period of hospitalisation, identical catchment areas of all study subjects and the relatively high response rate helped to minimise selection bias. In addition, the allele frequencies in the present study were corresponded to previous studies in Chinese population (23,38,39) , which suggested that selection bias may not be a serious problem. Besides, to reduce recall bias, cases were interviewed as soon as they were diagnosed with breast cancer (77•6 % of the cases were interviewed within 3 d after hospitalisation) and as far as possible before their surgery.…”

The CYP19A1 (TTTA)n Repeat Polymorphism, but not Arg264Cys Polymorphism, May Affect the Risk of Prostate Cancer: Evidence from a Meta-Analysis

“…The C→T transition (rs700519) in exon 7 of the CYP19A1 gene leads to a single amino acid substitution, of Arg by Cys, at codon 264, and the T allele has been reported to enhance aromatase enzymatic activity, affecting the conversion of androgens. This modi cation may alter the risk of several disorders, such as breast cancer, polycystic ovary syndrome (PCOS), and endometrial cancer [36][37][38][39]. The current metaanalysis failed to detect any association between the Arg264Cys polymorphism and the overall PCa risk.…”

Glutathione transferase and mammary tumors

“…Поліморфізм GST У жінок з Китаю однонуклеотидний поліморфізм (SNP) GSTP1 Val105Ile (rs1695) асоціювався з підвищеним ризиком до раку молочної залози серед носіїв гетерозигот A/G та A/G+G/G, ніж у гомозиготних носіїв G/G порівняно з контролем A/A. Авторами була встановлена також різниця в асоціації між rs1695 та раком молочної залози серед білих, африканців та азіатів, що можна пояснити різними етнічними ознаками цих груп населення (Pan et al, 2016).…”