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

The age-specific incidence rate of breast cancer in women rises until menopause, levels off and then rises again at a much lower rate indicating a possible hormonal influence on the disease risk. A large amount of evidence has implicated hormones and other compounds with oestrogen activity in the pathogenesis of certain endocrine cancers, particularly breast cancer. Widely dispersed hormone-like chemicals, capable of disrupting the endocrine system and interfering with proliferation, have been described. Compounds such as dioxins, some polychlorinated biphenyls and the plastic ingredient bisphenol-A have been shown to interfere with human reproduction and hormonal regulation. The levels of these foreign compounds as well as the levels of endogenous oestradiol may influence the risk of breast cancer. Endogenous oestradiol is synthesised in the ovarian theca cells of premenopausal women or in the stromal adipose cells of the breast of postmenopausal women and minor quantities in peripheral tissue. These cells, as well as breast cancer tissue, express all the necessary enzymes for this synthesis: CYP17, CYP11a, CYP19, hydroxysteroid hydrogenase, steroid sulphatase as well as enzymes further hydroxylating oestradiol such as CYP1A1, CYP3A4, CYP1B1. Polymorphisms in these enzymes may have a possible role in the link between environmental estrogens and hormone-like substances and the interindividual risk of breast cancer.
 ...
PMID:Molecular epidemiology of breast cancer: genetic variation in steroid hormone metabolism. 1076 42

The CYP17 gene encodes an enzyme involved in several critical steps of steroidogenesis. The promoter region of the CYP17 displays a single-nucleotide polymorphism, which is suspected to modulate the expression of the gene and thus may contribute in the interindividual variations of hormonal background. In agreement with this functional hypothesis, the MspA1+ allele (designated as A2) of the CYP17 was shown to render an increased risk of breast cancer (BC). However, the latter observation was disputed by a series of negative reports. Here, we re-evaluated the role of CYP17 MspA1 polymorphism in the BC susceptibility, using a non-traditional design of a case-control study. In addition to randomly selected 183 BC patients and 107 female middle-aged donors, we examined the groups with apparently extreme characteristics of either BC risk or BC resistance, namely the 57 bilateral breast cancer (biBC) patients and 75 elderly (>/=75 years old) tumor-free women. Neither BC nor biBC patients showed increased prevalence of 'unfavorable' A2 allele as compared with the non-affected cohorts. Moreover, the A2 variant was not significantly associated with the tumor size, nodal involvement and menopausal status in the patients either with the monolateral or bilateral disease. Thus, our data argue against the earlier reported role of the CYP17 in BC predisposition and progression. In addition, usual distribution of the CYP17 alleles in the elderly group indicates a neutral effect of this polymorphism on the longevity in females.
 ...
PMID:CYP17 polymorphism in the groups of distinct breast cancer susceptibility: comparison of patients with the bilateral disease vs. monolateral breast cancer patients vs. middle-aged female controls vs. elderly tumor-free women. 1084 Jan 58

Epidemiologic studies indicate that most risk factors for breast cancer are related to reproductive and hormonal factors. For a number of years, the mechanism for estrogens in carcinogenesis was thought to be that of mitotic stimulation, with the growth promotion of ductal epithelial cells harboring precursor mutations in the breast. However, evidence is now available that estrogens may act as initiators of cellular alterations and tumorigenesis. Investigation and measurement of serum levels of estrogens in epidemiologic studies may, therefore, be misleading, because they may reflect levels quite different from those of hormone metabolites to which the target tissue is exposed. Proportions of hormone metabolites may be estimated by evaluation of associations between breast cancer risk and genetic polymorphisms in enzymes involved in hormone metabolism. A number of molecular epidemiologic studies have been conducted to evaluate associations between polymorphic genes involved in steroid hormone metabolism (i.e., CYP17, COMT, CYP1A1, CYP19, GST, and MnSOD) that may account for a proportion of enzymatic variability, and results are discussed in this review. There are strengths and limitations to such an approach, foremost of which may be the lack of insight into the extent to which individual variability in estrogen exposure may be explained by allelic variation. Variability in other endogenous and exogenous factors that impact parent hormones and their metabolites along activation and conjugation pathways may also affect associations in case-control comparisons. This and other possible reasons for inconsistencies in results of molecular epidemiologic studies are discussed. Contributions from population-based studies and those from the laboratory may together move this field ahead and more clearly elucidate the basis of hormonally related cancers, identifying etiologic factors and susceptible populations for preventive strategies.
 ...
PMID:Molecular epidemiology of genetic polymorphisms in estrogen metabolizing enzymes in human breast cancer. 1096 24

To examine the association between breast cancer risk and a T-to-C substitution polymorphism at the 5' promoter region of CYP17, a case-control study was conducted at Aichi Cancer Center Hospital in Japan. Subjects were 144 histologically confirmed breast cancer patients diagnosed in the past 4 years and 166 hospital controls without cancer. Allele frequency among controls was 44.9% (95% confidence interval; 39.5 - 50.2) for C allele. Odds ratio (OR) of the polymorphism relative to TT-genotype was 0.97 (0.58 - 1.64) for TC-genotype and 0.81 (0.39 - 1.68) for CC-genotype. Subgroup analyses revealed that the OR was not statistically significant for the subgroups stratified by interval after diagnosis, age at menarche, age at first birth, menopausal status, body mass index, and mother / sisters' history of breast cancer. Consistent with previous studies conducted in other countries, the 5' promoter region polymorphism of CYP17 affected breast cancer risk of Japanese women to a limited extent. Although this is not a large-scale case-control study with population controls, these findings provide enough information to discourage further studies on the association between this polymorphism and breast cancer risk in Japan at large, and suggest that this polymorphism is useless for breast cancer risk estimation.
 ...
PMID:No association of the 5' promoter region polymorphism of CYP17 with breast cancer risk in Japan. 1101 Nov 14

A case-control study was conducted to investigate the association of two genetic polymorphisms (1931T/C and 1951G/A) in the promoter region of the CYP17 gene with breast cancer risk in Japanese women. No significant association was observed between CYP17 polymorphism(1951G/A) and breast cancer risk (odds ratio (OR) = 1.71, 95% confidence interval (CI): 0.28-1.84). In contrast, a significant increase in breast cancer risk (OR= 1.82. 95% CI: 1.07-3.12) was observed in CYP17(1931C/C) homozygotes compared with CYP17(1931T/C) heterozygotes and CYP17(1931T/T) homozygotes when women aged > or = 55 years were considered, but such a significant increase was not observed when women aged < or = 54 years were considered (OR = 0.96, 95% CI: 0.56-1.63). These results suggest that CYP17 polymorphism(1931T/C) would be useful in the selection of Japanese women at a high risk for developing breast cancer at the age of > or = 55 years.
 ...
PMID:Genetic polymorphism in CYP17 and breast cancer risk in Japanese women. 1109 12

The potential role of the polymorphism in the CYP17 gene was evaluated in a case-control study with 483 incident breast cancer patients and 482 population controls, all of homogenous Finnish origin. Our data disagree with the earlier suggestions that the minor A2 variant of CYP17 would pose an increased risk for developing advanced breast cancer. In contrast, a tendency of inverse association was found for premenopausal women carrying the A2 allele containing genotypes with a multivariate adjusted odds ratio of 0.58 approaching statistical significance (95% CI, 0.31-1.07). Agreeing with previous observations, the protective effect of later age at menarche (> or =13 years) was mainly limited to women with A1/A1 genotype, although this could only be seen in premenopausal women (odds ratio, 0.34; 95% CI, 0.15-0.76). Similarly, we found a remarkably lower risk for premenopausal women with at least one child (odds ratio, 0.22; 95% CI, 0.07-0.62) to be mainly attributable to the A1/A1 genotype. CYP17 genotypes may thus modify individual breast cancer proneness in certain subpopulations, although they appear not to have any major modifying role in the risk of this malignancy overall. Because these findings are based on relatively small numbers in stratified analysis, they should, however, be interpreted with caution before being confirmed in future studies.
 ...
PMID:Steroid metabolism gene CYP17 polymorphism and the development of breast cancer. 1114 20

We conducted a nested case-control study to evaluate whether polymorphisms in two genes involved in estrogen metabolism, CYP17 and HSD17B1, were useful in developing a breast cancer risk model that could help discriminate women who are at higher risk of breast cancer. If polymorphisms in these genes affect the level of circulating estrogens, they may directly influence breast cancer risk. The base population for this study is a multiethnic cohort study that includes African-American, Non-Latina White, Japanese, Latina, and Native Hawaiian women. For this analysis, 1508 randomly selected controls and 850 incident breast cancer cases of the first four ethnic groups who agreed to provide a blood specimen were included (76 and 80% response rates, respectively). The CYP17 A2 allele and the HSD17B1 A allele were considered "high-risk" alleles. Subjects were then classified according to number of high-risk alleles. After adjusting for age, weight, and ethnicity, we found that carrying one or more high-risk alleles increases the risk of advanced breast cancer in a dose-response fashion. The risk among women carrying four high-risk alleles was 2.21 [95% confidence interval (CI), 0.98-5.00; P for trend = 0.03] compared with those who carried none. This risk was largely limited to women who were not taking hormone replacement therapy (relative risk, 2.60; 95% CI, 0.95-7.14) and was most pronounced among those weighing 170 pounds or less (RR, 3.05; 95% CI, 1.29-7.25). These findings suggest that breast cancer risk has a strong genetic component and supports the theory that the underlying mechanism of "complex traits" can be understood using a multigenic model of candidate genes.
 ...
PMID:Building a multigenic model of breast cancer susceptibility: CYP17 and HSD17B1 are two important candidates. 1121 83

Among women, the A2 allele of CYP17 has been associated with elevated levels of endogenous steroid hormones; however, it does not seem to be a strong independent risk factor for breast cancer. We assessed the association between the A2 allele of CYP17 and invasive endometrial cancer risk in a case-control study nested within the Nurses' Health Study cohort (cases: n = 184; controls: n = 554). We also evaluated whether endometrial cancer risk associated with CYP17 genotype was modified by established endometrial cancer risk factors. In addition, we further examined the relationship between CYP17 genotype and endogenous plasma steroid hormone levels among postmenopausal controls not using hormone replacement therapy (HRT). Women with the A2 allele of CYP17 were at decreased risk of endometrial cancer (A1/A1 genotype (reference); A1/A2 genotype: odds ratio, 0.89; 95% confidence interval, 0.62-1.27; A2/A2 genotype: odds ratio, 0.43; 95% confidence interval, 0.23-0.80; P trend, 0.02). We also observed the inverse association between the A2 allele and endometrial cancer risk to be stronger among women with a first-degree family history of endometrial and/or colorectal cancer (P for interaction, 0.05). Among 165 controls, we did not observe women with the A2 allele to have significantly elevated levels of any steroid hormone fraction. When these women were combined and analyzed with those women on whom we had previously examined the relationship between CYP17 genotype and circulating hormone levels (total n = 469), only modest associations were observed for the A2/A2 genotype and steroid hormone fractions estrone (versus A1/A1 genotype: +10.9%; P = 0.05) and estradiol (+8.5%; P = 0.17). These data suggest that the A2 allele of CYP17 decreases endometrial cancer risk, but has only weak effects on endogenous estrogen levels among postmenopausal women.
 ...
PMID:A polymorphism in CYP17 and endometrial cancer risk. 1135 12

Endogenous estradiol is synthesized in the ovarian theca cells of premenopausal women or in the stromal adipose cells of the breast of postmenopausal women and in minor quantities in peripheral tissue. These cells, as well as breast cancer tissue, express all the necessary enzymes for this synthesis: CYP17, CYP11a, CYP19, hydroxysteroid hydrogenase, steroid sulphatase as well as enzymes further hydroxylating estradiol such as CYP1A1, CYP3A4, CYP1B1. Polymorphisms in these enzymes may have a possible role in the link between environmental estrogens and hormone-like substances and the interindividual risk of breast cancer.
 ...
PMID:[Genetic polymorphism and variability of steroid hormone metabolism: connection with risk of developing breast neoplasms]. 1138 50

Environmental chemicals with estrogenic activities have been suggested to be able to interact with the endocrine system. Endogenous estrogen is synthesized in the ovarian theca cells of premenopausal women or in the stromal adipose cells of the breast of postmenopausal women and minor quantities in peripheral tissue. These cells, as well as breast tissue, express all the necessary enzymes for this synthesis, CYP17, CYP11a, CYP19, 17-beta-hydroxysteroid hydrogenase, steroid sulfatase as well as enzymes further hydroxylating estradiol, such as CYP1A1, CYP3A4, CYP1B1, catechol-o-methyltransferase (COMT). Polymorphisms in these enzymes may have a possible role in the link between environmental estrogens and hormone-like substances and the interindividual risk of breast cancer.
 ...
PMID:Genetic susceptibility and environmental estrogen-like compounds. 1153 51


<< Previous 1 2 3 4 5 6 7 8 9 Next >>