Polymorphisms of estrogen receptor alpha in prostate cancer

Abstract

Estrogen receptor (ER) alpha polymorphisms have been shown to be involved in the oncogenesis of several organs. We hypothesize that polymorphisms of the ERalpha gene are risk factors for prostate cancer. The genotypic distributions of six different loci (codons: 10 T-->C, 87 G-->C, 243 C-->T, 325 C-->G, 594 G-->A, and intron 1 C-->T) of the ERalpha gene were analyzed in prostate cancer tissues. The DNA from 115 cases of prostate cancer (Japanese population) was analyzed by sequence-specific polymerase chain reaction (PCR) and direct sequencing to determine the genotypic and allelic frequencies of the six different polymorphic loci of ERalpha. The relative risk of variant genotype was calculated by comparison with 200 healthy controls. Results of this study showed that the frequency of the variant genotype (C/C) on codon 10 was significantly higher in prostate cancer patients. The odds ratio (OR) was calculated as 3.26 compared to wild-type (T/T) with a 95% confidence interval (CI) of 1.58-6.73. Allele frequency at codon 10 also differed between groups. No association was found between codon 10 polymorphism and the stage of cancer. Polymorphism was not observed in codon 87, and frequencies of genotypes and alleles at other loci (intron 1, codons 243, 325, and 594) were not statistically different between cancer and controls. The present study suggests that polymorphism in codon 10 of ERalpha may be a risk factor for prostate cancer. These results are important in understanding the role of ERalpha polymorphism in the pathogenesis of prostate cancer.

Estrogen and progesterone receptor gene polymorphisms and sporadic breast cancer risk: A Spanish case‐control study

“…The S10S polymorphism has been associated with a protective effect for other cancers such as endometrial cancer 17 and with increased risk for prostate and renal-cell carcinoma. 18,19 Based on these earlier studies and the confirmation in the present study, it seems plausible that the S10S variant or some other either in proximity, or in linkage disequilibrium with it, contributes to a decrease in breast cancer risk.…”

Prostate Cancer Risk and ESR1 TA, ESR2 CA Repeat Polymorphisms

“…The effects of these alleles can be expressed as relative odds associated with replacing one ESR1 (TA) 14 allele with one ESR1 (TA) 24 allele (odds ratio, 1.42; 95% confidence interval, 1.00-2.00; P = 0.05) or replacing one ESR1 (TA) 14 allele with one ESR1 (TA) 25 allele (odds ratio, 2.10; 95% confidence interval, 1.15-3.84; P = 0.02; Figs. 1 and 2).…”

“…One study has found an association between a polymorphism in codon 10 of ESR1 and prostate cancer risk (24). Another recent study detected an effect of a different ESR1 SNP (rs2234693) on prostate cancer grade at diagnosis, but not total risk of either familial or sporadic prostate cancer (25), and no association with one ERh SNP.…”

The role of estrogens and estrogen receptors in normal prostate growth and disease

“…Interestingly, ERα expression has been observed in some prostate cancer cell lines [86] as well as in hormone refractory and metastatic lesions suggesting its re-emergence as cancer progresses [87] although this has not been consistently seen in all studies [88]. It is also noteworthy that prostate cancer risk has been associated with genetic polymorphisms in the ERα gene particularly within Japanese and African American populations implicating a potential causal relationship between ERα mediated estrogenic action and prostate cancer [89,90].…”