Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    Keywords: CANCER ; MODEL ; COMMON ; RISK ; GENE ; GENES ; BIOLOGY ; ASSOCIATION ; SUSCEPTIBILITY ; VARIANTS ; FREQUENCIES ; BREAST ; breast cancer ; BREAST-CANCER ; ovarian cancer ; OVARIAN-CANCER ; genetics ; SNP ; cancer risk ; REPLICATION ; case-control studies ; molecular biology ; case-control study ; REGRESSION ; VARIANT ; SNPs ; GENOTYPE ; CANCER-RISK ; LOCI ; GENOME-WIDE ASSOCIATION ; genetic association ; Genetic ; Genome-wide association studies ; INVASIVE OVARIAN
    Abstract: Because both ovarian and breast cancer are hormone-related and are known to have some predisposition genes in common, we evaluated 11 of the most significant hits (six with confirmed associations with breast cancer) from the breast cancer genome-wide association study for association with invasive ovarian cancer. Eleven SNPs were initially genotyped in 2927 invasive ovarian cancer cases and 4143 controls from six ovarian cancer case-control studies. Genotype frequencies in cases and controls were compared using a likelihood ratio test in a logistic regression model stratified by study. Initially, three SNPs (rs2107425 in MRPL23, rs7313833 in PTHLH, rs3803662 in TNRC9) were weakly associated with ovarian cancer risk and one SNP (rs4954956 in NXPH2) was associated with serous ovarian cancer in non-Hispanic white subjects (P-trend 〈 0.1). These four SNPs were then genotyped in an additional 4060 cases and 6308 controls from eight independent studies. Only rs4954956 was significantly associated with ovarian cancer risk both in the replication study and in combined analyses. This association was stronger for the serous histological subtype [per minor allele odds ratio (OR) 1.07 95% CI 1.01-1.13, P-trend = 0.02 for all types of ovarian cancer and OR 1.14 95% CI 1.07-1.22, P-trend = 0.00017 for serous ovarian cancer]. In conclusion, we found that rs4954956 was associated with increased ovarian cancer risk, particularly for serous ovarian cancer. However, none of the six confirmed breast cancer susceptibility variants we tested was associated with ovarian cancer risk. Further work will be needed to identify the causal variant associated with rs4954956 or elucidate its function
    Type of Publication: Journal article published
    PubMed ID: 19304784
    Signatur Availability
    BibTip Others were also interested in ...
  • 2
    Keywords: CANCER ; neoplasms ; RISK ; RISKS ; SAMPLE ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; single nucleotide polymorphism ; BREAST ; breast cancer ; BREAST-CANCER ; NO ; ovarian cancer ; OVARIAN-CANCER ; REDUCED RISK ; COLORECTAL-CANCER ; cancer risk ; EPITHELIAL-CELLS ; CANCER RISKS ; REPLICATION ; GROWTH-FACTOR-BETA ; SUSCEPTIBILITY GENE ; HETEROGENEITY ; ONCOLOGY ; RE ; BRCA2 ; SINGLE NUCLEOTIDE POLYMORPHISMS ; SNPs ; SINGLE-NUCLEOTIDE POLYMORPHISMS ; analysis ; USA ; CANDIDATE ; CANCER-RISK ; COMMON VARIANT ; CASP8 GENE ; GENOME-WIDE ASSOCIATION ; association study ; CONSORTIUM ; NUCLEOTIDE
    Abstract: The Ovarian Cancer Association Consortium selected 7 candidate single nucleotide polymorphisms (SNPs), for which there is evidence from previous studies of an association with variation in ovarian cancer or breast cancer risks. The SNPs selected for analysis were F31I (rs2273535) in AURKA, N372H (rs144848) in BRCA2, rs2854344 in intron 17 of RB1, rs2811712 5' flanking CDKN2A, rs523349 in the 3' UTR of SRD5A2, D302H (rs1045485) in CASP8 and L10P (rs1982073) in TGFB1. Fourteen studies genotyped 4,624 invasive epithelial ovarian cancer cases and 8,113 controls of white non-Hispanic origin. A marginally significant association was found for RB1 when all studies were included [ordinal odds ratio (OR) 0.88 (95% confidence interval (CI) 0.79-1.00) p = 0.041 and dominant OR 0.87 (95% CI 0.76-0.98) p = 0.025]; when the studies that originally suggested an association were excluded, the result was suggestive although no longer statistically significant (ordinal OR 0.92, 95% CI 0.79-1.06). This SNP has also been shown to have an association with decreased risk in breast cancer. There was a suggestion of an association for AURKA, when one study that caused significant study heterogeneity was excluded [ordinal OR 1.10 (95% CI 1.01-1.20) p = 0.027; dominant OR 1.12 (95% CI 1.01-1.24) p = 0.03]. The other 5 SNPs in BRCA2, CDKN2A, SRD5A2, CASP8 and TGFB1 showed no association with ovarian cancer risk; given the large sample size, these results can also be considered to be informative. These null results for SNPs identified from relatively large initial studies shows the importance of replicating associations by a consortium approach. (C) 2008 Wiley-Liss, Inc
    Type of Publication: Journal article published
    PubMed ID: 18431743
    Signatur Availability
    BibTip Others were also interested in ...
  • 3
    Keywords: CANCER ; RISK ; GENE ; BIOMARKERS ; ASSOCIATION ; polymorphism ; SUSCEPTIBILITY LOCUS ; BREAST ; HEALTH ; MUTATIONS ; ENVELOPE ; GENOME-WIDE ASSOCIATION ; SYNE-1 ; CANDIDATE SNPS ; single nucleotide
    Abstract: We genotyped 13 single nucleotide polymorphisms (SNPs) in the estrogen receptor alpha gene (ESR1) region in three population-based case-control studies of epithelial ovarian cancer conducted in the United States, comprising a total of 1,128 and 1,866 non-Hispanic white invasive cases and controls, respectively. A SNP 19 kb downstream of ESR1. (rs2295190, G-to-T change) was associated with invasive ovarian cancer risk, with a per-T-allele odds ratio (OR) of 1.24 [95% confidence interval (CI), 1.06-1.44, P = 0.0061. rs2295190 is a nonsynonymous coding SNP in a neighboring gene called spectrin repeat containing, nuclear envelope I (SYNE1), which is involved in nuclear organization and structural integrity, function of the Golgi apparatus, and cytokinesis. An isoform encoded by SYNE1 has been reported to be down-regulated in ovarian and other cancers. rs2295190 was genotyped in an additional 12 Studies through the Ovarian Cancer Association Consortium, with 5,279 invasive epithelial cases and 7,450 controls. The per-T-allele OR for this 12-study set was 1.09 (95% CI, 1.02-1.17; P = 0.017). Results for the serous subtype in the 15 combined studies were similar to those overall (n = 3,545; OR, 1.09; 95% Cl, 1.01-1.18; P = 0.025), and our findings were strongest for the mucinous subtype (n = 447; OR, 1.32; 95% CI, 1.11-1.58; P = 0.002). No association was observed for the endometrioid Subtype. In an additional analysis of 1,459 borderline ovarian cancer cases and 7,370 controls, rs2295190 was not associated with risk. These data provide suggestive evidence that the rs2295190 T allele, or another allele in linkage disequilibrium with it, may be associated with increased risk of invasive ovarian cancer. Cancer Epidemiol Biomarkers Prev; 190); 245-50. (C) 2010 AACR
    Type of Publication: Journal article published
    PubMed ID: 20056644
    Signatur Availability
    BibTip Others were also interested in ...
  • 4
    Keywords: CANCER ; PROSTATE ; RISK ; BIOMARKERS ; ASSOCIATION ; SUSCEPTIBILITY ; BREAST ; CONSORTIUM ; MULTIPLE
    Abstract: Background: We previously reported an association between rs2660753, a prostate cancer susceptibility polymorphism, and invasive epithelial ovarian cancer (EOC; OR = 1.2, 95% CI = 1.0-1.4, P-trend = 0.01) that showed a stronger association with the serous histological subtype (OR = 1.3, 95% CI = 1.1-1.5, P-trend = 0.003). Methods: We sought to replicate this association in 12 other studies comprising 4,482 cases and 6,894 controls of white non-Hispanic ancestry in the Ovarian Cancer Association Consortium. Results: No evidence for an association with all cancers or serous cancers was observed in a combined analysis of data from the replication studies (all: OR = 1.0, 95% CI = 0.9-1.1, P-trend = 0.61; serous: OR = 1.0, 95% CI = 0.9-1.1, P-trend = 0.85) or from the combined analysis of discovery and replication studies (all: OR = 1.0, 95% CI = 1.0-1.1, P-trend = 0.28; serous: OR = 1.1, 95% CI = 1.0-1.2, P-trend = 0.11). There was no evidence for statistical heterogeneity in ORs across the studies. Conclusions: Although rs2660753 is a strong prostate cancer susceptibility polymorphism, the association with another hormonally related cancer, invasive EOC, is not supported by this replication study. Impact: Our findings, based on a larger sample size, emphasize the importance of replicating potentially promising genetic risk associations.
    Type of Publication: Journal article published
    PubMed ID: 21415361
    Signatur Availability
    BibTip Others were also interested in ...
  • 5
    Keywords: EXPRESSION ; VARIANTS ; BREAST ; IDENTIFICATION ; Hox genes ; GENOME-WIDE ASSOCIATION ; RISK LOCI ; LONG-RANGE INTERACTION ; ANALYSES REVEAL ; FALLOPIAN-TUBE
    Abstract: Genome-wide association studies have reported 11 regions conferring risk of high-grade serous epithelial ovarian cancer (HGSOC). Expression quantitative trait locus (eQTL) analyses can identify candidate susceptibility genes at risk loci. Here we evaluate cis-eQTL associations at 47 regions associated with HGSOC risk (P 〈= 10(-5)). For three cis-eQTL associations (P〈1.4 x 10(-3), FDR〈0.05) at 1p36 (CDC42), 1p34 (CDCA8) and 2q31 (HOXD9), we evaluate the functional role of each candidate by perturbing expression of each gene in HGSOC precursor cells. Overexpression of HOXD9 increases anchorage-independent growth, shortens population-doubling time and reduces contact inhibition. Chromosome conformation capture identifies an interaction between rs2857532 and the HOXD9 promoter, suggesting this SNP is a leading causal variant. Transcriptomic profiling after HOXD9 overexpression reveals enrichment of HGSOC risk variants within HOXD9 target genes (P = 6 x 10(-10) for risk variants (P〈10(-4)) within 10 kb of a HOXD9 target gene in ovarian cells), suggesting a broader role for this network in genetic susceptibility to HGSOC.
    Type of Publication: Journal article published
    PubMed ID: 26391404
    Signatur Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...