Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The cytochrome P450 family (CYPs) and the glutathione S-transferase (GSTs) enzymes play an important role in the metabolism of environmental carcinogens and of oestrogen and can affect breast cancer risk. In this study we examine the role of the genes CYP1A1, CYP17, CYP2D6, GSTM1, GSTP1 and GSTT1 in breast cancer risk in Brazilian women. The study population consisted of 102 incident breast cancer cases and 102 healthy controls. Genotyping analyses were performed by PCR-based methods. A significant finding was observed between GSTP1 Ile-Val polymorphism and breast cancer risk (OR = 1.81; CI 95% = 1.04-3.16). A significant association was observed between women with 0-2 risk genotypes and those with 4 or more risk genotypes (OR = 2.42; CI 95% = 1.13-5.18) when the potential combined effects of the risk genotypes were examined. No significant differences between cases and controls were found correlating the genotypes and the clinical-histopathological parameters. In conclusion, in our population only GSTP1 was associated with breast cancer risk. However, when the genes were tested in combination, a significant association in the breast cancer risk was observed.
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PMID:Genetic polymorphisms in oestrogen metabolic pathway and breast cancer: a positive association with combined CYP/GST genotypes. 1861 15

Estrogen plays a role in breast cancer development, and genetic polymorphisms in estrogen receptor gene ER-alpha and genes regulating estrogen biosynthesis and metabolisms are associated with the risk of breast cancer in women in western countries. Therefore, we hypothesized that SNPs in ER-alpha and other estrogen-metabolizing genes contribute to breast cancer risk in Chinese women. In this study, we genotyped polymorphisms in the regulatory regions of ER-alpha (rs3798577) and other two estrogen-metabolizing enzyme genes CYP17 (rs743572) and CYP19 (rs10046) among 300 breast cancer cases and 390 controls in a Chinese population. Crude and adjusted odds ratios (aORs) and 95% confidence intervals (CIs) were calculated by unconditional logistic regression analyses to estimate breast cancer risk associated with these polymorphisms. We found that the T allele frequency of ER-alpha was significantly higher in cases (59.8%) than controls (54.5%) (P = 0.047), but no significant difference was found in the genotype distribution. However, postmenopausal breast cancer risk was associated with the CYP17 TC genotype (aOR = 1.77, 95% CI = 1.11-2.83) compared with the TT genotype. The CYP19 variant TC + TT genotypes were associated with both overall cancer risk (TT + TC vs. TT aOR = 1.73, 95% CI = 1.13-2.65) and premenopausal cancer risk (TT + TC vs. TT aOR = 1.78, 95% CI = 1.03-3.09), particularly for ER +/PR + tumors. Furthermore, there were joint effects between CYP19 T and ER-alpha T variant genotypes (aOR = 1.67, 95% CI = 1.03-2.69 for CYP19 TC + TT vs. CC among ER-alpha T variant carriers) and between CYP19 T and CYP17 C variant genotypes (aOR = 1.77, 95% CI = 1.11-2.83 for CYP19 TC + TT vs. CC among CYP17 variant C carriers). This study provides evidence that polymorphisms CYP17 rs743572, CYP19 rs10046 and ER-alpha rs3798577 are associated with breast cancer risk among Chinese women.
Breast Cancer Res Treat 2009 Mar
PMID:Association of genetic polymorphisms of ER-alpha and the estradiol-synthesizing enzyme genes CYP17 and CYP19 with breast cancer risk in Chinese women. 1862 29

Breast cancer is the most common female cancer and the second cause of cancer death in women. Despite recent breakthroughs, much of the etiology of this disease is unknown and the most important risk factor, i.e., exposure to endogenous and exogenous estrogen throughout life cannot explain the heterogeneity of prognosis nor clinical features of patients. Recently, many gene polymorphisms in the metabolism of breast cancer have been described as possible neoplasm etiologic factors. This review is an attempt to summarize the current knowledge about these polymorphisms and to determine new target genes for diagnosis and treatment of the disease. Polymorphisms in the genes CYP17, CYP19, CYP1A1, CYP1A2, CYP1B1, UGT1A1, SULT1A1, 17-hydroxysteroid-dehydrogenase, COMT, GST, ESR1, and ESR2 are described.
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PMID:Genetic polymorphisms, the metabolism of estrogens and breast cancer: a review. 1871 61

Radiologic breast density is one of the predictive factors for breast cancer and the extent of the density is directly related to postmenopause. However, some patients have dense breasts even during postmenopause. This condition may be explained by the genes that codify for the proteins involved in the biosynthesis, as well as the activity and metabolism of steroid hormones. They are polymorphic, which could explain the variations of individual hormones and, consequently, breast density. The constant need to find markers that may assist in the primary prevention of breast cancer as well as in selecting high risk patients motived this study. We determined the influence of genetic polymorphism of CYP17 (cytochrome P450c17, the gene involved in steroid hormone biosynthesis), GSTM1 (glutathione S-transferase M1, an enzyme involved in estrogen metabolism) and PROGINS (progesterone receptor), for association with high breast density. One hundred and twenty-three postmenopausal patients who were not on hormone therapy and had no clinical or mammographic breast alterations were included in the present study. The results of this study reveal that there was no association between dense breasts and CYP17 or GSTM1. There was a trend, which was not statistically significant (P = 0.084), towards the association between PROGINS polymorphism and dense breasts. However, multivariate logistic regression showed that wild-type PROGINS and mutated CYP17, taken together, resulted in a 4.87 times higher chance of having dense breasts (P = 0.030). In conclusion, in the present study, we were able to identify an association among polymorphisms, involved in estradiol biosyntheses as well as progesterone response, and radiological mammary density.
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PMID:Polymorphism in CYP17, GSTM1 and the progesterone receptor genes and its relationship with mammographic density. 1933 Feb 59

Estrogen and its metabolites are believed to play important roles in breast cancer, and its determinants include both genetic and lifestyle factors. The objective of the study is to investigate the association of breast cancer risk in Thailand with genetic polymorphisms in several genes involved in estrogen synthesis and metabolism. Five hundred and seventy patients with histopathologically confirmed breast cancer and 497 controls were included in the present study. Forty single nucleotide polymorphisms (SNPs) in the CYP1A1, CYP1A2, CYP1B1, CYP17, CYP19, CYP2C9, CYP2C19, AhR, ESR1, PGR, ERRG, COMT, HSD17B1, HSD17B2, EPHX1 and NQO1 genes were genotyped. Association of genotypes with breast cancer risk was evaluated using multivariate logistic regression, which suggested an altered risk for the following SNPs [gene, odds ratio (OR) and 95% confidence interval are shown]: heterozygote carriers of rs4917623 [CYP2C19, OR = 1.38 (1.04-1.84)], rs2066853 [AhR, OR = 1.34 (1.02-1.76)] and rs1857407 [ERRG, (OR = 0.72 (0.55-0.96)]; homozygote carriers of rs762551 [CYP1A2, OR = 2.75 (1.47-5.14)], rs4917623 [CYP2C19, OR = 1.48 (1.00-2.19) and rs945453 [ERRG, OR = 1.66 (1.04-2.65)]. In addition, a stratified analysis by menopausal status indicated that the association of the CYP1A2 (rs762551) and CYP17 (rs743572) polymorphisms with breast cancer risk were mainly evident in premenopausal, while ERRG (rs1857407) was significant in postmenopausal women. These findings suggest that CYP1A2, CYP2C19, AhR, ERRG and CYP17 polymorphisms may play an important role in estrogen metabolism and modify individual susceptibility to breast cancer in Thai women.
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PMID:Genetic polymorphisms of estrogen metabolizing enzyme and breast cancer risk in Thai women. 1941 45

Breast cancer is initiated by exposure to endogenous and exogenous estrogens. A case-control (n= 250-500) study was undertaken to investigate the role of Single Nucleotide Polymorphisms (SNP's) in CYP17 (T34C), CYP19 (Trp39Arg) and FGFR2(C906T). Genotyping was done using the Taqman allelic discrimination assay for CYP17 (T34C) and FGFR2 (T906C) and PCR-CTPP for CYP19 (Trp39Arg). There was a significant protective association of the (TT/CC) genotype of the CYP17 gene against the risk of developing breast cancer (OR= 0.68, 95% CI: 0.49-0.96), which was more significant in postmenopausal women (OR= 0.56, 95% CI: 0.35-0.89) (p= 0.015). CYP19 (Trp39Arg) is a rare polymorphism and all the cases were homozygous for the wild type Trp allele (100%); this was also the case for 99.2% of the controls. We were unable to detect any variant form of the CYP19 gene in south Indian women. There was no significant association between the risk of breast cancer and FGFR2 (C906T). These results suggest that the CYP17 TT/CC genotype is associated with decreased risk for breast cancer, especially in post menopausal women.
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PMID:CYP17 (T34C), CYP19 (Trp39Arg), and FGFR2 (C906T) polymorphisms and the risk of breast cancer in south Indian women. 1946 36

Long-term hormone therapy (HT) is a recognized risk factor for postmenopausal breast cancer. Elevated steroid hormone levels play a critical role in breast carcinogenesis and this may be contributed by the efficiency of hormone biosynthesis. Within this context, genetic polymorphisms related to steroid hormone biosynthesis may modify HT-associated postmenopausal breast cancer risk. CYP17 is a key player of this pathway and the CYP17A1_-34_T > C polymorphism has been suggested to affect breast cancer risk in women using long-term HT. We genotyped 13 polymorphisms of seven genes of the steroid hormone biosynthesis pathway in 3,149 postmenopausal breast cancer patients and 5,489 age-matched controls from Germany. We observed a significant interaction of CYP17A1_-34_T > C and HT use on breast cancer risk in a co-dominant model (P (interaction) = 0.007). Current users of estrogen monotherapy showed a significantly increased risk for duration of use per 5-year increment when they were carriers of the CYP17A1_-34_TC genotype (OR 1.13, 95% CI: 1.04-1.23 per 5 years of use). We conclude that CYP17A1_-34_T > C may be part of the genetic background to contribute to postmenopausal breast cancer risk in women using estrogen monotherapy.
Breast Cancer Res Treat 2010 Apr
PMID:Postmenopausal estrogen monotherapy-associated breast cancer risk is modified by CYP17A1_-34_T>C polymorphism. 1967 5

This case control study investigated whether polymorphisms of estrogen metabolizing genes CYP1A1 MspI, CYP17 MspAI, COMT Val(158) Met, and SULT1A1 Arg(213) His have any role in familial breast cancer susceptibility risk. Logistic regression analysis adjusted to age was used to calculate odds ratios (ORs) and 95% confidence intervals (95%CIs). Familial breast cancer risk due to CYP1A1 wt/m1 and m1/m1 genotypes was 2.3 (1.51-3.61)-fold and 7.1 (3.69-13.7)-fold, respectively. In addition to the main effects, certain first-order interactions were also significantly associated with familial breast cancer. Our results favor a possible risk modification by estrogen metabolizing gene polymorphisms in familial breast cancer susceptibility.
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PMID:Possible risk modification by polymorphisms of estrogen metabolizing genes in familial breast cancer susceptibility in an Indian population. 1986 50

Epidemiological studies have evaluated the association between CYP17 MspA1 polymorphism and breast cancer risk. However, the results remain conflicting rather than conclusive. To derive a more precise estimation of the relationship, we performed this meta-analysis. Systematic searches of the PubMed and Medline databases were performed. A total of 35 studies including 22,090 cases and 28,498 controls were identified. Genotype distributions of CYP17 in the controls of all studies were in agreement with Hardy-Weinberg equilibrium (HWE) except for three studies. When all 35 studies were pooled into the meta-analysis, there was no evidence for significant association between CYP17 MspA1 polymorphism and breast cancer risk (for A1/A2 vs. A1/A1: OR = 1.00, 95% CI = 0.96-1.04; for A2/A2 vs. A1/A1: OR = 1.03, 95% CI = 0.97-1.08; for dominant model: OR = 1.01, 95% CI = 0.97-1.05; for recessive model: OR = 1.03, 95% CI = 0.98-1.08). In the subgroup analyses by ethnicity, menopausal status and source of controls, no significant associations were found in all genetic models. When sensitivity analyses were performed by excluding HWE-violating studies, all the results were not materially altered. In summary, the meta-analysis strongly suggests that CYP17 MspA1 polymorphism is not associated with increased breast cancer risk.
Breast Cancer Res Treat 2010 Jul
PMID:Lack of association between CYP17 MspA1 polymorphism and breast cancer risk: a meta-analysis of 22,090 cases and 28,498 controls. 2003 66

A number of studies have been investigated the association between CYP17 T34C polymorphism and the risk of breast cancer; the results of these studies are inconsistent, however. This fact implies that the effect of CYP17 T34C polymorphism on susceptibility to breast cancer may be modified by other risk factors. In order to provide a more definitive conclusion, a full meta-analysis combining and summarizing 24 studies was first performed. Both traditional method and Bayesian approach were applied. Odds ratio was estimated using a dominant mode of inheritance after a biological justification for the choice of genetic model. The results of homogeneity analysis (H = 1.16, I (2) = 25.4%, and P = 0.127) suggested the presence of heterogeneity across the studies. Thus, random effects models simulated by the DerSimonian-Laird method were employed. The capability of a Bayesian approach was highlighted in the estimation of a pooled odds ratio and 95% confidence interval. The results of meta-analysis (OR = 1.001, CI = 0.832-1.208) suggest no significant association in the combined populations. Furthermore, Bayesian meta-regression and subgroup analysis were conducted to investigate the sources of heterogeneity. The risk factors evaluated in the study were menopausal status, ethnicity, age at menarche, age at first birth, parity, use of oral contraceptives, body mass index (BMI), and use of hormone repair therapy (HRT). After these population stratifications, there was evidence indicating that a possible impact of menopausal status, age at menarche, and BMI on the association between CYP17 T34C polymorphism and the risk of breast cancer.
Breast Cancer Res Treat 2010 Jul
PMID:Factors influencing the association between CYP17 T34C polymorphism and the risk of breast cancer: meta-regression and subgroup analysis. 2004 6


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