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Query: UMLS:C1140680 (ovarian cancer)
 28,141 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genetic alterations have been frequently found in ovarian cancer. There is some indirect evidence indicating that mutation of the steroid receptor genes may play a role in the carcinogenesis of ovarian cancer. Human androgen receptor (hAR) gene mutations have been found in up to 50% of hormone-relapsed prostate cancer. The role of hAR mutation and its association with decreased expression in ovarian cancer has never been elucidated. In this study mutations of hAR gene in 38 human ovarian cancer cell lines with different AR expression pattern were studied using SSCP. No mutation of the hAR gene was found. Mutation of hAR gene is an infrequent event and therefore unlikely to be involved in the development of ovarian cancer. The decreased expression of hAR in advanced ovarian tumor is not due to genetic aberration of hAR. Mutation screening of hAR may not provide any information for risk assessment of developing ovarian cancer.
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PMID:Androgen receptor gene mutations do not occur in ovarian cancer. 1081 Mar 59

Epidemiological studies indicate that ovarian cancer is an endocrine-related tumour. We conducted a case-control comparison to assess the androgen receptor (AR) exon 1 polymorphic CAG repeat length (CAG(n)) as a risk factor for epithelial ovarian cancer. AR CAG(n) was determined for 319 case subjects with ovarian adenocarcinoma and 853 unaffected control subjects (comprising 300 unrelated adult female monozygotic twins, and 553 adult females sampled randomly from the population using the electoral rolls). The CAG(n) distributions of case subjects and control subjects were compared as a continuum, and by dichotomising alleles according to different CAG(n) cut-points. Logistic regression was used to calculate age-adjusted odds ratio (OR) estimates. Analyzed as a continuous variable, there was no difference between case subjects and control subjects for the smaller, larger or average allele sizes of the CAG(n) genotype, before or after adjusting for age. The mean (95% CI) for the average CAG(n) was 22.0 (21.8-22.2) for case subjects and 22.0 (21.9-22.1) for control subjects (p>.9). Analysis of CAG(n) as a dichotomous variable showed no difference between case subjects and control subjects for the median cutpoint (>/= 22), or for another cut-point previously reported to act as a modifier of breast cancer risk (>/= 29). Our data provide no evidence for an association between ovarian cancer risk and the genotype defined by the AR exon 1 CAG(n) polymorphism, although we cannot exclude small effects, or threshold effects in a small subgroup.
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PMID:Androgen receptor exon 1 CAG repeat length and risk of ovarian cancer. 1092 55

Breast cancer is a rare disease in men. Germ-line mutations in BRCA2 and androgen receptor (AR) genes are thought to be responsible for a proportion of male breast cancer cases. The present study was performed on a series of 37 consenting patients not selected for family history of breast/ovarian cancer. The entire coding region of the BRCA2 gene and two exons of the AR gene were analyzed for germ-line mutations to evaluate the association between BRCA2 and AR genes and male breast cancer in Poland. We identified four frameshift mutations (11%) in exons 10, 11, 17 and 18, two of them were novel: 6495del3insC and 8457insA. Three missense unclassified variants (8%) of the BRCA2 gene were also identified. The frequencies of missense alterations were examined in a set of 200 chromosomes. No alteration of the AR gene was found. We did not observe much difference in clinicopathological features between carriers and non-carriers of BRCA2 mutations. Five of 37 patients (14%) had a family history of breast cancer, in one first- or second-degree relative, among the latter was one mutation carrier. The results of this study suggest that germ-line BRCA2 mutations account for rather small proportion of male breast cancer in Poland.
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PMID:BRCA2 germline mutations in male breast cancer patients in the Polish population. 1113 48

Our objectives were to test whether polymorphic variation in the (CAG)n repeat of the androgen receptor (AR) gene affects penetrance of germ-line BRCA mutations for ovarian cancer or age of diagnosis for ovarian cancer. Using a case-series study design, 179 consecutive Ashkenazi Jewish ovarian cancer patients were genotyped for AR repeat length and BRCA mutation status. There was no association between AR repeat length and presence of a BRCA mutation. However, ovarian cancer patients from both groups (with or without BRCA mutation) who carried a short AR allele were diagnosed an average of 7.2 (95% confidence interval, 2.3-12.1) years earlier than patients who did not carry a short allele (P = 0.004). These data suggest that AR allele length affects age of diagnosis of ovarian cancer, irrespective of BRCA mutation status.
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PMID:The androgen receptor and genetic susceptibility to ovarian cancer: results from a case series. 1122 80

The human androgen receptor (AR) gene contains a highly polymorphic CAG repeat in exon 1 that is inversely correlated with AR transcriptional activity in vitro. Several studies have shown that fewer CAG repeats are associated with an increased risk as well as more aggressive forms of prostate cancer. More recently, AR allele length was also inversely correlated with the histological grade of breast cancer, but no association was found between the AR-CAG polymorphism and the risk of either breast or ovary cancer. On the contrary, it was proposed that a longer CAG repeat sequence might be associated with an increased risk of breast cancer in BRCA1 mutation carriers, thus suggesting a different role of the AR-CAG polymorphism in sporadic and inherited breast cancers. With the intent of better understanding the role of the AR-CAG polymorphism as a cancer risk modifier, we defined the AR genotype of 151 patients (101 with breast and 50 with ovary cancer) belonging to high-risk breast/ovary cancer families. No difference in CAG repeat length was found between either breast and ovary cancer patients or age at diagnosis of both tumors. These results were also confirmed in a sub-group of 47 breast cancer cases, that either carried a BRCA gene mutation (11 cases) or were identified by very stringent operational criteria as hereditary breast cancers. Even though a substantially larger sample size would be required to reach conclusive evidence, our findings suggest that the AR-CAG polymorphism does not act as a modifier of tumor onset or tumor phenotype in breast/ovarian cancer families.
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PMID:Lack of association between androgen receptor CAG polymorphism and familial breast/ovarian cancer. 1136 74

Variation in the penetrance estimates for BRCA1 and BRCA2 mutations carriers suggests that other genetic polymorphisms may modify the cancer risk in carriers. A previous study has suggested that BRCA1 carriers with longer lengths of the CAG repeat in the androgen receptor (AR) gene are at increased risk of breast cancer (BC). We genotyped 188 BRCA1/2 carriers (122 affected and 66 unaffected with breast cancer), 158 of them of Ashkenazi origin, 166 BC cases without BRCA1/2 mutations and 156 Ashkenazi control individuals aged over 56 for the AR CAG and GGC repeats. In carriers, risk analyses were conducted using a variant of the log-rank test, assuming two sets of risk estimates in carriers: penetrance estimates based on the Breast Cancer Linkage Consortium (BCLC) studies of multiple case families, and lower estimates as suggested by population-based studies. We found no association of the CAG and GGC repeats with BC risk in either BRCA1/2 carriers or in the general population. Assuming BRCA1/2 penetrance estimates appropriate to the Ashkenazi population, the estimated RR per repeat adjusted for ethnic group (Ashkenazi and non-Ashkenazi) was 1.05 (95%CI 0.97-1.17) for BC and 1.00 (95%CI 0.83-1.20) for ovarian cancer (OC) for CAG repeats and 0.96 (95%CI 0.80-1.15) and 0.90 (95%CI 0.60-1.22) respectively for GGC repeats. The corresponding RR estimates for the unselected case-control series were 1.00 (95%CI 0.91-1.10) for the CAG and 1.05 (95%CI 0.90-1.22) for the GGC repeats. The estimated relative risk of BC in carriers associated with > or =28 CAG repeats was 1.08 (95%CI 0.45-2.61). Furthermore, no significant association was found if attention was restricted to the Ashkenazi carriers, or only to BRCA1 or BRCA2 carriers. We conclude that, in contrast to previous observations, if there is any effect of the AR repeat length on BRCA1 penetrance, it is likely to be weak.
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PMID:CAG and GGC repeat polymorphisms in the androgen receptor gene and breast cancer susceptibility in BRCA1/2 carriers and non-carriers. 1143 99

Biodistribution of two 18F-labeled androgens and an 124I/125I-labeled androgen were studied in five androgen receptor (prostate) animal models with or lacking sex hormone binding globulin (SHBG). As models for androgen-receptor positive ovarian cancer, xenografts of three human ovarian cancer cell lines were tested in SCID mice. SHBG in the prostate model systems significantly affects the metabolism, clearance, and distribution of the radiolabeled androgens in several tissues, but ovarian cancer animal models were disappointing.
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PMID:Comparison of animal models for the evaluation of radiolabeled androgens. 1151 42

The CAG repeat (CAGn) present in the N-terminal region of the androgen receptor (AR) inversely correlates with AR transactivation activity. The aim of this study was to investigate whether polymorphic variation in the CAGn length is associated with the risk of developing ovarian cancer. Using a case-control study design 121 women with histologically confirmed ovarian cancer and 100 controls (healthy women) were genotyped for AR-CAG length. No marked difference in the mean length of CAGn was observed between ovarian cancer patients and controls. However, when considering patients with positive personal or family history of tumor (PPFHT), the mean lengths of the long allele, the short allele and the average of the 2 alleles were longer than in the controls. Odds ratios (OR) and their corresponding 95% confidence intervals (CI) were computed after allowance for age. We observed an increase in the risk of ovarian cancer, in terms of OR, in women with CAGn >or=22 (OR=2.17, 95% CI:1.10-4.27). The increase of relative risk was particularly high in women with CAGn >or=22 belonging to the PPFHT group: OR=3.52 (95% CI 1.18-10.47). We also found a statistically significant trend (chi2 trend=4.91; p=0.03) towards an increased risk of ovarian cancer with increasing CAGn length (from <or=21 to 22-23, 24-25 and >or=26). Again, a strong association between increase in CAGn and risk of ovarian cancer was observed in PPFHT patients (chi2 trend=6.38; p=0.01). The results suggest that AR-CAG repeat length could play a role as modifier of the ovarian cancer risk conferred by highly penetrant genes rather than itself conferring a low risk.
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PMID:Polymorphic CAG repeat length within the androgen receptor gene: identification of a subgroup of patients with increased risk of ovarian cancer. 1195 43

We previously reported the identification of three minimal regions of deletion on the short arm of chromosome 3 (3p) in epithelial ovarian tumor specimens, suggesting that the inactivation of tumor-suppressor genes in these regions may be important in terms of ovarian tumorigenesis. Another previous study of ovarian cancer observed that allele loss of chromosome 179 was frequently found in ovarian tumors that also showed loss of heterozygosity (LOH) of chromosomes 3p, 13q, 17p, and Xp. In an independent study, we also reported a high frequency of LOH for selected chromosome 17 loci in high-grade and late-stage ovarian tumors. We have extended our LOH analysis of chromosome 3p to include 102 ovarian tumor specimens (29 and 73 samples were previously examined for LOH of chromosome 3p and 17 markers, respectively), using additional polymorphic markers, to assess the coordinate LOH of loci representing the three chromosome 3p minimal regions of deletions [von Hippel-Lindau syndrome (VHL), thyroid hormone receptor beta, and fragile histidine triad (FHIT)] and LOH of other important loci [tumor protein 53 (TP53), breast cancer 1 early onset (BRCA1), breast cancer 2 early onset, retinoblastoma 1, ornithine carbamoyltransferase, and androgen receptor] or somatic mutations in TP53. There was a significant association between LOH of any chromosome 3p marker and LOH of any chromosome 17 marker (P = 0.026). The frequency of LOH at the TP53 locus was higher in the group of samples that displayed LOH of a 3p marker (P = 0.019), as was the frequency of LOH at the BRCA1 locus (P = 0.014). LOH of chromosome 3p was noted in four specimens that did not display LOH of either the BRCA1 or the TP53 locus, indicating that LOH of these loci need not precede LOH of the chromosome 3p loci. We found a significant association between LOH of the VHL (3p25) locus and LOH of any chromosome 17 marker (P = 0.005), suggesting that there may be an important relationship, in the tumorigenesis of epithelial ovarian cancer, between a gene at 3p25 and a gene located on chromosome 17. Our results indicate that inactivation of p53 by somatic mutation is unlikely to be a prerequisite to chromosome 3p LOH, because we found no significant association between mutations in TP53 and LOH of the three chromosome 3p loci. The frequency of LOH at the FHIT locus at 3p14 increased significantly with advancing age at diagnosis (P = 0.018), as did the frequency of somatic TP53 mutations (P = 0.008).
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PMID:Comparative analysis of loss of heterozygosity of specific chromosome 3, 13, 17, and X loci and TP53 mutations in human epithelial ovarian cancer. 1211 14

BRCA1/2 mutation carriers are at an increased risk for developing breast and/or ovarian cancer. Yet, the genetic and environmental factors that govern the phenotypic expression of mutant BRCA1/2 alleles remain elusive. The CAG repeat within exon 1 of the androgen receptor (AR) gene is reportedly associated with breast cancer phenotype in BRCA1 mutation carriers. Two hundred and twenty seven BRCA1/2 mutation carriers were genotyped for the polymorphic AR CAG repeat, and allele size was correlated with breast/ovarian cancer morbidity parameters. Of 227 BRCA1/2 carriers, 169 were BRCA1 mutation carriers and 58 carried a BRCA2 mutation, 149 had breast and/or ovarian cancer and 78 were asymptomatic mutation carriers. The mean age at diagnosis in women with either or both neoplasms was 46.7+/-11.2 years, and that of the asymptomatic group - 45.8+/-9.4 years, a statistically insignificant difference. The AR CAG repeat ranged from eight to 28 in all tested women, and the mean number of the repeats were not statistically different between affected (18.3+/-2.4) and asymptomatic mutation carriers (18.6+/-2.1). The AR CAG repeat among patients with early onset (<42 years) breast cancer was significantly shorter (17.5+/-2.3) compared with asymptomatic individuals (18.6+/-2.1) (P<0.01), and the shorter allele - the younger the age at diagnosis. There is no conclusive evidence of association between AR CAG repeat size and breast or ovarian cancer risk in Jewish BRCA1/2 mutation carriers. A small effect of a short AR CAG allele size on breast cancer at early age (<42 years) cannot be excluded.
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PMID:Androgen receptor CAG repeat length in Jewish Israeli women who are BRCA1/2 mutation carriers: association with breast/ovarian cancer phenotype. 1240 4


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