Estrogen Receptor Gene Polymorphisms Research Articles

Interaction of interleukin-6 and estrogen receptor gene polymorphisms on bone mass accrual in Chinese adolescent girls

We assessed the main and interaction effects of interleukin-6 and estrogen receptor gene polymorphisms on bone mass accrual in Chinese adolescent girls. A total of 228 premenarche Chinese girls (9-11.5 years old) were recruited for a 2-year follow-up study. Bone mineral density (BMD) at the total body, lumbar spine (L1-L4), and total left hip were measured by dual-energy X-ray absorptiometry at baseline and follow-up. The -174G/C and -634C/G polymorphism of IL-6 gene, and PvuII and XbaI polymorphisms of the estrogen receptor (ER)-alpha gene, were determined. The -634C/G polymorphism of the IL-6 gene and PvuII polymorphism of ER-alpha gene were significantly associated with bone mass accrual after adjusting the potential confounding factors. Girls with pp genotype of ER-alpha gene had greater percentage accrual in BMD of total body (P = 0.010) and femoral intertrochanter (P = 0.038) than their PP and Pp counterparts. Girls with CC genotype of IL-6 -634G/C gene had higher percentage accrual in BMD of total body (P = 0.032) and femoral trochanter (P = 0.048) than their CG + GG counterparts. Significant interaction effects of IL-6 -634C/G polymorphism and ER-alpha PvuII polymorphism were observed on percentage change in BMD of total left hip (P = 0.009) and femoral intertrochanter (P = 0.007). The genotype CC (IL-6 -634C/G) x pp (ER-alpha PvuII) was associated with greater BMD accrual than other genotype combination in Chinese adolescent girls. We found that the IL-6 -634C/G and ER-alpha PvuII polymorphism were significantly associated with BMD accrual and that they have an interactional effect on BMD accrual in Chinese adolescent girls.

MUC1 and estrogen receptor α gene polymorphisms in dry eye patients

Dry eye syndrome is a collection of common disorders of multifactorial etiology. Although the epidemiology of dry eye has been well studied, reports of genetic patterns that might influence susceptibility to dry eye are few. We reported that the frequency of non-Sjögren's aqueous-deficient dry eye patients expressing only the MUC1/A splice variant of the mucin MUC1 may be lower than that of a normal control group [Imbert, Y., Darling, D.S., Jumblatt, M.M., Foulks, G.N., Couzin, E.G., Steele, P.S., Young, W.W., Jr., 2006. MUC1 splice variants in human ocular surface tissues: possible differences between dry eye patients and normal controls. Exp. Eye Res. 83, 493–501]. Also, He et al. [He, Y., Li, X., Bao, Y., Sun, J., Liu, J., 2006. The correlation of polymorphism of estrogen receptor gene to dry eye syndrome in postmenopausal women. Yan. Ke. Xue. Bao. 22, 233–236] reported a difference between Chinese dry eye and control groups in the frequency of a polymorphism in estrogen receptor α (ERα). In the present study we determined the statistical significance and generality of these observations and tested if the MUC1 splice variant difference between subject groups reflected a difference in the MUC1 variable number of tandem repeat (VNTR) size class. There was a perfect correlation between the MUC1/A or MUC1/B splice variant pattern and the SNP genotype frequency of the SNP (rs4072037) controlling that splicing event. In contrast, western and Southern blotting indicated that MUC1 VNTR size class corresponded to the MUC1 SNP genotype in only 80% of cases. We determined the status of the MUC1 SNP in normal and dry eye populations all of whom were female Caucasians. The MUC1 SNP genotype frequency of the normal control group was statistically different from both the non-Sjögren's aqueous-deficient dry eye group with ocular surface staining (P=0.017) and the evaporative dry eye group (P=0.015). We also tested SNP rs2234693 to analyze the polymorphism in the ERα gene and found no significant difference in the SNP genotype frequency between the control group and either of the dry eye subtypes. Thus, among Caucasians there is no evidence for an association of the ERα gene polymorphism with dry eye syndrome as previously described in a Chinese population. In conclusion, the etiologies of evaporative dry eye and non-Sjögren's aqueous-deficient dry eye are known to be different. However, our results suggest that both of these subtypes of dry eye disease may share a common mechanism or factor related to MUC1 genotypic differences that affects susceptibility to ocular surface damage. This altered susceptibility may not be related to the MUC1 VNTR size class. Therefore, mechanisms influencing protection of the ocular surface against inflammation and damage in different types of dry eye disease warrant further investigation particularly in relation to MUC1 genotype.

Genetic polymorphisms of ESR1 and ESR2 that may influence estrogen activity and the risk of hypospadias

The etiology of hypospadias is regarded as a complex disorder with both genetic and environmental contributions. Although alterations in androgen activity have been associated with hypospadias, few associations with estrogen activity have been documented. Here, we assessed genetic polymorphisms in estrogen receptor genes and their association with hypospadias. Using a case-control study of 59 cases with hypospadias and 286 controls, we examined the association of hypospadias with the following polymorphisms: PvuII and XbaI in ESR1, and 2681-4A>G in ESR2. For the cases, we found a negative association with the G allele containing variants of ESR1 XbaI (OR = 0.52, P < 0.05), and a negative association with the G allele containing variants of ESR2 2681-4A>G (OR = 0.59, P < 0.05). For the cases, we also identified a negative association with the CG haplotype, and a positive association with the CA haplotype, defined by ESR1 PvuII and XbaI (P < 0.05). These findings suggest that the G allele containing variants of ESR1 XbaI and the G allele containing variants of ESR2 2681-4A>G may decrease the risk of hypospadias, whereas the ESR1 C-A haplotype may increase its risk.

Estrogen Receptor Alpha and Beta Gene Polymorphisms Are Not Risk Factors for Recurrent Miscarriage in a Brazilian Population

The aim of this study was to determine the prevalence of alpha (ESR1: c.454-397T>C and c.454-351A>G) and beta (ESR2: 1082G>A and 1730G>A) estrogen receptor gene polymorphisms in 2 Brazilian ethnic groups (Caucasian, African Brazilian) and to investigate their association with recurrent miscarriage (RM) in 75 women with a history of 3 or more consecutive pregnancy losses and 139 controls with at least 2 live births and no history of pregnancy loss. Polymerase chain reaction and restriction fragment length polymorphism were used to identify gene polymorphisms. Coagulation methods were used to measure protein C, protein S, and fibrinogen, and a chromogenic method was used for antithrombin quantification. Significantly higher prevalences of 1082G>A and 1730G>A polymorphisms were seen in African Brazilian and Caucasian controls, respectively. There was no association between RM and ESR polymorphisms. There was a difference in the genotype prevalence in the c.454-39T>C polymorphism between RM and control Caucasians, but this finding was not associated with an increased risk of miscarriage. There was no synergistic or additive effect between ESR polymorphisms and thrombophilia in RM patients. A difference in the prevalence of ESR polymorphisms was observed, according to ethnic origin. ESR polymorphisms could not be considered a risk factor for RM.

Interactions Between Effects of Estrogen Receptor Gene Polymorphisms on BMD and Experiences of the First Spermorrhea in Chinese Han Boys

To study the interaction between polymorphisms of estrogen receptor (ER) gene and puberty on bone mineral density (BMD). One hundred and forty-six boys aged 13-17 years were divided into two groups according to their first spermorrhea. DNA was analyzed for Xba I and Pvu II genotypes by PCR-RFLP. BMD of the total body, forearm and lumbar spine was measured by dual-energy X-ray absorptiometry (DXA). The relationship between polymorphisms of ER gene and BMD in these two groups was analyzed. The BMD at all sites in the spermorrhea group was significantly higher than that in the un-spermorrhea group. The independent contribution of ER genotypes to BMD at two pubertal stages was analyzed after adjusting co-variables. In the un-spermorrhea group, the BMD at distal 1/10 and 1/3 forearm of those carrying pp genotype was significantly higher than that of the non-carries, whereas in the spermorrhea group BMD in those carrying the same genotype was significantly lower than that in the non-carriers. Similar results were obtained by haplotype analysis. Multiple stepwise regression analysis showed that body weight, age and the first spermorrehea were the dominant determinants for BMD. BMD at forearm might be influenced by interaction between ER genotype and the first spermorrehea. The polymorphisms of ER gene play a different role in BMD influenced by the first spermorrhea. Chinese boys carrying p or x allele should pay more attention to their bone mass.

Intron 1 and exon 1 alpha estrogen receptor gene polymorphisms in women with endometriosis

To evaluate the association of intron 1 and exon 1 polymorphisms in the estrogen receptor alpha gene (ER-alpha) with endometriosis in women. Association study. Endometriosis Unit, Federal University of São Paulo. The control group consisted of volunteers older than 45 years who had no evidence of endometriosis antecedents. Two groups with the disease were evaluated: the first group had stage I or II endometriosis and the second group stage III or IV. Polymerase chain reaction (PCR) followed by digestion with HaeIII and MspI endonucleases (RFLP) were applied to detect intron 1 and exon 1 polymorphisms, respectively, in a total of 125 controls and 105 affected women. Frequency and distribution of HaeIII and MspI polymorphisms in ER-alpha. No significant differences in the frequency of polymorphisms either in intron 1 or exon 1 of ER-alpha were found when endometriosis patients were compared with control subjects. Furthermore, the frequency of ER-alpha polymorphisms within the two different groups of patients with disease was statistically similar. The odds ratio between presence of intron 1 single-nucleotide polymorphisms (SNP) and endometriosis was 0.904, and the odds ratio between exon 1 SNP and endometriosis was 0.976. The evaluated polymorphisms were not associated with endometriosis.

Impact of estrogen receptor gene polymorphisms and mRNA levels on obesity and lipolysis – a cohort study

BackgroundThe estrogen receptors α and β (ESR1, ESR2) have been implicated in adiposity, lipid metabolism and feeding behaviour. In this report we analyse ESR1 and ESR2 gene single nucleotide polymorphisms (SNPs) for association with obesity. We also relate adipose tissue ESR1 mRNA levels and ESR1 SNPs to adipocyte lipolysis and lipogenesis phenotypes.Methods23 ESR1 and 11 ESR2 tag-SNPs, covering most of the common haplotype variation in each gene according to HAPMAP data, were analysed by Chi2 for association with obesity in a cohort comprising 705 adults with severe obesity and 402 lean individuals. Results were replicated in a cohort comprising 837 obese and 613 lean subjects. About 80% of both cohorts comprised women and 20% men. Adipose tissue ESR1 mRNA was quantified in 122 women and related to lipolysis and lipogenesis by multiple regression. ESR1 SNPs were analysed for association with adipocyte lipolysis and lipogenesis phenotypes in 204 obese women by simple regression.ResultsNo ESR1 SNP was associated with obesity. Five ESR2 SNPs displayed nominal significant allelic association with obesity in women and one in men. The two ESR2 SNPs associated with obesity with nominal P value < 0.01 were genotyped in a second cohort where no association with obesity was observed. There was an inverse correlation between ESR1 mRNA levels in abdominal subcutaneous (sc) adipose tissue and basal lipolysis, as well as responsiveness to adrenoceptor agonists independent of age and BMI (P value 0.009–0.045). ESR1 rs532010 was associated with lipolytic sensitivity to noradrenaline (nominal P value 0.012), and ESR1 rs1884051 with responsiveness to the non-selective beta-adrenoceptor agonist isoprenaline (nominal P value 0.05). These associations became non-significant after Bonferroni correction.ConclusionESR1 gene alleles are unlikely to be a major cause of obesity in women. A minor importance of ESR2 on severe obesity cannot be excluded. The inverse correlation between ESR1 mRNA levels and lipolytic responsiveness to adrenoceptor agonists implies that low adipose tissue ESR1 levels attenuate catecholamine resistance in sc fat cells of obese women hereby contributing to loss of sc and gain of visceral fat. There is no evidence for a genetic impact of ESR1 on lipolysis or lipogenesis.

Association of estrogen receptor gene polymorphism and intrahepatic cholestasis of pregnancy

目的 研究雌激素受体α(estrogen receptor α,Erα)基因多态性表达,探讨ER基因多态性与江西籍汉族人群妊娠期肝内胆汁淤积症(intrahepatic cholestasis of pregnancy,ICP)的相关关系.方法 应用聚合酶链反应、限制性片段长度多态性分析方法分析Erα基因多态性在ICP人群中的分布规律以及Erα基因型、等位基因与ICP的相关关系.结果 (1)Erα基因XbaⅠ位点多态性在ICP组和对照组的之间有统计学意义.(2)Erα基因PvuⅡ位点多态性在ICP组和对照组的比较中无统计学意义.(3)ICP组中,突变杂合子基因型Xx的OR值为3.429(95%CI:1.509-7.791),XX、Xx联合分析OR值为3.143(95%CI:1.431-6.905)ICP组和对照组Erα XbaⅠ等位基因频率比较发现X等位基因的相对危险度是x等位基因的2.071倍.(4)PvuⅡ和XbaⅠ联合基因型分布在ICP组和对照组间有统计学差异,杂合子联合基因型PpXx与野生型ppxx之间的差异在ICP组和对照组中有统计学意义,OR值为3.956(95%CI:1.287-12.157).结论 Erα基因XbaⅠ酶切位点限制性片段长度多态性与江西籍汉族人群ICP的发生之间存在相关性.而PvuⅡ酶切位点限制性片段长度多态性与该病无关.X等位基因是ICP发病的易感基因,Xx基因型为易感基因型,单倍体PpXx可能使ICP发病风险升高。

Association of aromatase and estrogen receptor gene polymorphisms with hip fractures

Two polymorphisms of the aromatase and estrogen receptor genes appeared to interact to influence the risk of hip fractures in women. Allelic variants of the aromatase gene have been associated with bone mineral density and vertebral fractures. Our objective was to analyze the relationship between two polymorphisms of the aromatase and estrogen receptor genes and hip fractures. We studied 498 women with hip fractures and 356 controls. A C/G polymorphism of the aromatase gene and a T/C polymorphism of the estrogen receptor alpha gene were analyzed using Taqman assays. Aromatase gene expression was determined in 43 femoral neck samples by real-time RT-PCR. There were no significant differences in the overall distribution of genotypes between the fracture and control groups. However, among women with a TT genotype of the estrogen receptor, the CC aromatase genotype was more frequent in women with fractures than in controls (39 vs. 23%, p = 0.009). Thus, women homozygous for T alleles of estrogen receptor and C alleles of aromatase were at increased risk of fracture (odds ratio 2.0; 95% confidence interval 1.2-3.4). The aromatase polymorphism was associated with RNA levels in bone tissue, which were three times lower in samples with a CC genotype (p = 0.009). These common polymorphisms of the aromatase and estrogen receptor genes appear to interact, influencing the risk of hip fractures in women.

Effect of Soy Isoflavones on Endometriosis

Progression of endometriosis is considered estrogen-dependent. Dietary soy isoflavones may affect the risk of endometriosis, and polymorphisms in estrogen receptor genes may modify this association. We examined associations among soy isoflavone intake, estrogen receptor 2 (ESR2) gene polymorphisms and risk of endometriosis. We recruited women age 20-45 years old who had consulted a university hospital for infertility in Tokyo, Japan in 1999 or 2000. A total of 138 eligible women were diagnosed laparoscopically and classified into 3 subgroups: control (no endometriosis), early endometriosis (stage I-II) and advanced endometriosis (stage III-IV). We measured urinary levels of genistein and daidzein as markers for dietary intake of soy isoflavones, and genotyped ESR2 gene RsaI polymorphisms. Higher levels of urinary genistein and daidzein were associated with decreased risk of advanced endometriosis (P for trend = 0.01 and 0.06, respectively) but not early endometriosis. For advanced endometriosis, the adjusted odds ratio for the highest quartile group was 0.21 (95% confidence interval = 0.06-0.76) for genistein and 0.29 (0.08-1.03) for daidzein, when compared with the lowest group. Inverse associations were also noted between urinary isoflavones and the severity of endometriosis (P for trend = 0.01 for genistein and 0.07 for daidzein). For advanced endometriosis, ESR2 gene RsaI polymorphism appeared to modify the effects of genistein (P for interaction = 0.03). Dietary isoflavones may reduce the risk of endometriosis among Japanese women.

Associação entre os polimorfismos HaeIII e MspI do gene para o receptor alfa de estrogênio e densidade mamográfica em mulheres após a menopausa

OBJETIVO: Avaliar a presença dos polimorfismos HaeIII e MspI do gene para o receptor de estrogênio alfa, bem como fatores clínicos e suas possíveis associações com a densidade mamográfica em mulheres após a menopausa. MÉTODOS: Foram avaliadas 115 mulheres após a menopausa, não usuárias de terapia hormonal e sem lesão mamária clínica ou mamograficamente identificada. A densidade mamográfica foi determinada por três observadores independentes, tomando-se como base a classificação dos padrões mamográficos do ACR-BIRADS®, 2003 (duas avaliações subjetivas e uma computadorizada - Adobe Photoshop® 7.0). Amostras de raspado bucal foram obtidas para extração de DNA e em seguida foi realizada uma PCR-RFLP (Polymerase Chain Reation - Restriction Fragment Length Polymorphism) para análise de polimorfismos presentes no íntron 1 e éxon 1 do gene do REalfa (HaeIII e MspI). RESULTADOS: O polimorfismo HaeIII foi encontrado em 43 (37,4%) das 115 mulheres, ao passo que o MspI estava presente em 96 (83,5%) das mesmas. Houve alto grau de concordância entre os três observadores na determinação da densidade mamográfica. Trinta e quatro (29,6%) mulheres tinham mamas densas, e 81 (70,4%), mamas lipossubstituídas. CONCLUSÃO: Não houve associação entre o polimorfismo HaeIII do gene para o receptor de estrogênio alfa e densidade mamográfica (Fisher = 0,712). Houve associação próxima à significância estatística entre o polimorfismo MspI e densidade (Fisher = 0,098). Idade, paridade e índice de massa corporal mostraram-se associados com densidade mamográfica.

Comparative analysis of estrogen receptor gene polymorphisms in apes

Polymorphic microsatellite repeats in the promoter region of estrogen receptor alpha gene (ESRalpha and the intron 6 region of estrogen receptor beta gene (ESRbeta) have been reported in human populations. To examine the evolutional state of both repeats, we surveyed the corresponding regions in DNA sequences from the following great apes and gibbons: 56 chimpanzees, 3 bonobos, 16 gorillas, 20 orangutans and 60 gibbons (four species: 17 of Hylobates agilis, 11 of H. lar, 15 of H. muelleri, and 17 of H. syndactylus). In the corresponding region of the TA repeat of human ESRalpha, chimpanzees and bonobos had two motifs in the repeat tract, (TA)(7-9) and (CA)(4-6). Gorillas had the (TA)(9-10) repeat tracts and orangutans had monomorphic (TA)(7) repeats. Although all great apes maintained the TA expansion, all gibbon sequences contained (TA)(2), implying that the CA dinucleotide expansion arose in the ancestor of chimpanzees and bonobos. The nucleotide sequences of ESRbeta showed a very complex repeat pattern in apes. The human sequences had a non-variable preceding sequence at (CA)(n), (GA)(2)(TA)(8)(CA)(4)(TA). In apes that region included {(TA)(n)(CA)(n)}(n). Gibbon sequences included (TATG)(n) and (TATC)(n) and no regular construction was observed. A deletion event in the reverse primer site seems to have occurred in the orangutan lineage. In addition, a great diversity of allele length was detected in each gibbon species.

Endogenous Estradiol and Its Association with Estrogen Receptor Gene Polymorphisms

We evaluated potential associations between single nucleotide polymorphism (SNP) variants of the estrogen receptor genes ESR1 and ESR2 and circulating estradiol (E 2) concentrations in women of 4 races/ethnicities. The study population was drawn from participants in the Study of Women’s Health Across the Nation (SWAN). A total of 1,538 African American, Caucasian, Chinese, and Japanese women from SWAN participated in the Sex Steroid Hormone Genetics Protocol by providing blood for sex steroid hormone analyses and consenting to lymphocyte transformation from which DNA was extracted and genotyped. We evaluated 4 ESR1 SNPs ( ESR1 rs9340799, ESR1 rs2234693, ESR1 rs728524, and ESR1 rs3798577), and 3 ESR2 SNPs ( ESR2 rs1255998, ESR2 rs1256030, and ESR2 rs1256065). Mean E 2 level was 196.0 ± 4.0 pmol/L in women who were premenopausal and perimenopausal (with blood drawn on days 2 through 5 of the menstrual cycle follicular phase); however, mean E 2 levels in Chinese and Japanese women were lower (155.7 ± 10.6 pmol/L and 170.0 ± 10.3 pmol/L, respectively) than in African American (196.4 ± 8.1 pmol/L, P <0.05) or Caucasian women (210.7 ± 5.9 pmol/L, P <0.002). The ESR1 rs3798577 CC genotype was associated with lower circulating E 2 concentrations in African American women ( P <0.07) and explained about 1% of the variation in circulating E 2 concentrations. In Japanese women, the GC genotype of ESR2 rs1255998 was associated with significantly lower circulating E 2 concentrations that explained about 4% of the variation. Circulating E 2 concentrations were not strongly or consistently associated with selected polymorphisms for the estrogen receptor genes. The 2 strongest associations explained <4% of the total variation in the circulating E 2 concentrations.

The Association of Bone Mineral Density with Estrogen Receptor Gene Polymorphisms

The purpose of this investigation was to evaluate single nucleotide polymorphism (SNP) variants of the estrogen receptor genes ESR1 and ESR2 and bone mineral density (BMD) of the lumbar spine (LS-BMD) or total hip (hip BMD) in women of 4 races/ethnicities who were premenopausal or in early perimenopause. The sample consisted of 1,301 participants from the Study of Women’s Health Across the Nation (SWAN) with measures of BMD and genotyping; of these, 295 were African American, 693 were Caucasian, 151 were Chinese, and 162 were Japanese. We evaluated the potential association of LS-BMD or hip BMD with 4 SNPs from the ESR1 gene ( ESR1 rs9340799, ESR1 rs2234693, ESR1 rs728524, and ESR1 rs3798577), and 3 SNPs from the ESR2 gene ( ESR2 rs1255998, ESR2 rs1256030, and ESR2 rs1256065). Unadjusted mean LS-BMD values ranged from 1.141 ± 0.14 g/cm 2 in African American women to 1.031 ± 0.11 g/cm 2 in Japanese women; unadjusted mean hip BMD values ranged from 1.053 ± 0.14 g/cm 2 in African American women to 0.862 ± 0.10 g/cm 2 in Chinese women. African American and Japanese women with the ESR1 rs2234693 ( PvuII) CC genotype had higher LS-BMDs than did their peers with the TT genotype ( P = 0.009 and P = 0.04, respectively). Japanese women with the ESR1 rs3798577 CC or TC genotypes had lower LS-BMD than did Japanese women with the TT genotype ( P = 0.02 and P = 0.01, respectively). Caucasian women with the TC genotype for ESR2 rs1256030 had lower LS-BMDs than did those with the CC genotype ( P = 0.02). Chinese women who were heterozygous for ESR2 rs1256030 or ESR2 rs1256065 had significantly higher LS-BMDs and hip BMDs than did the referent groups for each of these SNPs ( CC and AA, respectively). Associations between BMD and ESR1 and ESR2 genotypes varied by race/ethnicity and by bone site. Our results differ from those previously reported for 2 ESR1 genotypes ( ESR1 rs2234693 [ PvuII] and ESR1 rs9340799 [ XbaI]). Moreover, 2 ESR1 and 3 ESR2 SNPs we studied have not previously been examined with respect to BMD. Among these, ESR2 rs1256030 and ESR2 rs1256065 appear to have an effect at both the lumbar spine and hip in Chinese women and may warrant further study.

Polymorphisms in estrogen-metabolizing and estrogen receptor genes and the risk of developing breast cancer among a cohort of women with benign breast disease

BackgroundA cohort study was conducted to examine the role of genetic polymorphisms in three estrogen metabolizing enzymes (COMT, CYP1A1, CYP1B1) and the two estrogen receptors (ESR1, ESR2) in the progression of benign breast disease (BBD) to breast cancer.MethodsAmong participants in an ongoing cohort study, 1438 Caucasian women had a breast biopsy for BBD and were successfully genotyped for at least one of the polymorphisms examined in this study. Genotypes were determined using DNA extracted from blood specimens collected in 1989. Incident cases of breast cancer occurring subsequent to BBD diagnosis up to 2003 were identified through cancer registries.ResultsAmong all participants, the ESR2 *5772G allele was associated with a significant decrease in the risk of breast cancer among women with BBD (Odds Ratio (OR) 0.38; 95% Confidence Interval (CI) 0.15, 0.96). Compared to the reference wild-type genotypes, marginally significant associations with the development of breast cancer were observed between carriers of the variant ESR1 – 104062T allele (OR 0.70, 95% CI 0.45, 1.09), the variant ESR2 *38A allele (OR 1.40; 95% CI 0.88, 2.25), and the variant CYP1B1 453Ser allele (OR 1.48, 95% CI 0.95, 2.32).ConclusionThe results indicate that specific polymorphisms in the CYP1B1, ESR1, and ESR2 genes may play a role in progression of BBD to breast cancer among Caucasian women. Although additional studies are needed to confirm or refute our findings, these results suggest that genetic markers may aid in the identification of women who are at risk for progression of BBD to cancer.

Vitamin D and estrogen receptor gene polymorphisms and the risk of colorectal cancer in Bulgaria

Different epidemiological studies report the protective effect on colorectal cancer (CRC) exerted by vitamin D(3) intake, estrogen replacement therapy, and increase of the risk of microsatellite instability (MSI) in CRC by withdrawal of estrogens. The aim of our study was to search for association between CRC and polymorphisms in estrogen receptor-alpha (ER-alpha) and Vitamin D receptor (VDR) genes. We analyzed the PvuII and XbaI polymorphisms from the ER-alpha gene and the BsmI polymorphism of the VDR gene in 140 patients with CRC (subsequently divided according to their MSI status) and 94 controls. We have demonstrated that the presence of the PvuII pp genotype increased the risk of developing MSI(+) tumors about three times compared to MSI(-) tumors [odds ratio (OR)=3.09, 95% confidence interval (CI) 0.88-10.91]. The effect of the XbaI xx genotype was similar (OR=2.08, 95% CI 0.49-8.81). Our results for the VDR BsmI polymorphism showed an increased risk for CRC in bb carriers (OR=1.8, 95% CI 0.81-4.05). We conclude that PvuII and XbaI polymorphisms in the ER-alpha gene were associated with the risk of developing MSI in CRC patients. The BsmI polymorphism in the VDR gene was linked to the risk of developing CRC.

Association between breast cancer and estrogen receptor gene polymorphism PVU II

643 Background: The estrogen receptor (ER) is well acknowledged as a prognostic factor in breast cancer, and it is a prerequisite to use the predictive information for hormonal therapy. We investigated whether that the different polymorphisms of the estrogen receptor could influence its expression or functionality. Methods: DNA was extracted from white blood cells of 236 breast cancer patients and 236 healthy, matched controls. The ER genotypes were determined by polymerase chain reaction (PCR) amplification followed by restriction enzyme digestion of the PCR product. Results were shown by electrophoreses. Clinical data such as histologic types, pTNM stage and patients age were available for statistical analyses. Results: We found a statistically significant correlation between the estrogen receptor polymorphism pattern and breast cancer. The receptor type PP was detected statistically significantly more often in postmenopausal breast cancer patients (PP vs pp+Pp, p =0.03). However, there was no correlation to the histobiochemical receptor status or UICC-Stadium. Conclusions: These results show an association between the estrogen receptor polymorphism and breast cancer. It seems to be that a complete lack of the p-allel is a risk factor to develop breast cancer at postmenopausal age. There was no influence on estrogen receptor expression or clinical tumor stage. Thus, we propose that there is no clinical use for estrogen receptor polymorphism analyses at this stage. No significant financial relationships to disclose.

Association of Estrogen Receptor Gene Polymorphisms With Susceptibility to Adolescent Idiopathic Scoliosis

A case-control study is presented. To investigate the association of estrogen receptor gene polymorphisms with adolescent idiopathic scoliosis (AIS) risk. Previous studies have shown that genetic factors are important in the pathogenesis of idiopathic scoliosis. Only 1 publication suggested that XbaI site polymorphism was associated with curve severity of idiopathic scoliosis. However, to our knowledge, the relationship of estrogen receptor gene polymorphisms and the individual susceptibility to idiopathic scoliosis has not been studied. This study included 202 patients with AIS and 174 healthy controls. Height, menarche status, curve pattern, Cobb angle, and Risser sign in female patients were recorded. There were 2 polymorphic loci, PvuII and XbaI locus, of estrogen receptor analyzed by restriction fragment length polymorphisms. The frequency of XX genotype was significantly higher in patients than that in controls (P = 0.005). The X allele appeared to be overrepresented in patients compared with controls (P = 0.001). Furthermore, the frequencies of XX genotype in female patients whose height was > or = 160 cm and Cobb angle > or = 40 degrees were higher than those whose height was <160 cm and Cobb angle <40 degrees (P = 0.001 and P < 0.001, respectively). The XbaI site polymorphism of estrogen receptor gene may be associated with a risk of AIS.

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

Estrogens, and to a lesser extent progesterones, influence the proliferation, differentiation and physiology of breast tissue as well as the development and progression of breast cancer. Genetic variants in the steroid hormone receptor genes ESR1 and PGR (belonging to the nuclear receptor superfamily) could therefore modify sporadic breast cancer susceptibility. Two studies have shown a protective effect associated with variants in ESR1 in 2 distinct populations. We studied 4 single nucleotide polymorphisms (SNPs) in ESR1 and 4 in PGR in 550 consecutive and unrelated sporadic Spanish breast cancer patients and 564 healthy Spanish controls. We observed a dominant protective effect for the S10S variant in ESR1, with an estimated odds ratio (OR) of 0.75 (95% CI = 0.58-0.97; p = 0.03) although functional studies did not show changes in the RNA stability. A small subset of individuals carried a haplotype combination that corroborates this protection. No other SNP considered in either gene was found to be associated with sporadic breast cancer. Our results obtained in a European population confirm the protective role of the S10S variant in ESR1, previously reported in an Asian and a European-American population.

Estrogen receptor gene polymorphisms are associated with recurrence of endometriosis

The presence of gene polymorphisms of the estrogen receptors ERalpha (PvuII and XbaI) and ERbeta (AluI) in 61 women with endometriosis was investigated. A statistically significant correlation between PvuII ERalpha gene polymorphism (PvuII), both in homozygosity (PP) and in heterozygosity (Pp), and a recurrence of endometriosis was found. In conclusion, women affected by endometriosis with the ERalpha polymorphic allele, even if heterozygous, have a worse prognosis, and these results suggest that the ERalpha gene polymorphisms may be included among the genetic risk factors for endometriosis.