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  • cancer risk  (4)
  • 1
    Keywords: CANCER ; DIAGNOSIS ; LUNG-CANCER ; HISTORY ; RISK ; GENE ; GENES ; METABOLISM ; GENETIC POLYMORPHISMS ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; SUSCEPTIBILITY ; BREAST ; breast cancer ; BREAST-CANCER ; DELETION ; MUTANT ; GLUTATHIONE ; AGE ; smoking ; cancer risk ; CARRIERS ; case-control studies ; TOBACCO ; CANCER-RESEARCH ; M1 ; glutathione-S-transferase ; GLUTATHIONE S-TRANSFERASE ; case-control study ; ENVIRONMENTAL CARCINOGENS ; GSTM1 ; GSTT1 ; METAANALYSIS ; CLASS-MU ; GSTT1 POLYMORPHISMS
    Abstract: The glutathione S-transferase (GST) genes are involved in the metabolism of various carcinogens. Deletion polymorphisms in the genes GSTM1 and GSTT1 and a base transition polymorphism at codon 105 (Ile--〉Val) in GSTP1 were investigated in relation to breast cancer risk. Tobacco smoking and reproductive factors were examined as potential effect modifiers. Individual data from seven case-control studies were pooled within the International Collaborative Study on Genetic Susceptibility to Environmental Carcinogens. To measure the effect of GSTs on breast cancer risk, odds ratios and 95% confidence intervals were computed adjusting for study center and age. The modifying effect was investigated by stratification on variables of smoking habits and reproductive history. A total of 2,048 cases with breast cancer and 1,969 controls were analyzed. The relative odds ratio (95% confidence interval) of breast cancer was 0.98 (0.86-1.12) with the GSTM1 null, 1.11 (0.87-1.41) with the GSTT1 null, 1.01 (0.79-1.28) with GSTP1 heterozygous mutants, and 0.93 (0.62-1.38) with GSTP1 homozygous mutants. Stratification by smoking or reproductive factors did not reveal a modifying effect of these variables, nor was there any association between GSTM1 and age at diagnosis of breast cancer. This is the largest study investigating susceptibility to breast cancer due to polymorphisms in the GST genes. The results conclusively show that single gene GST polymorphisms do not confer a substantial risk of breast cancer to its carriers. Furthermore, GSTs did not interact with smoking or reproductive history to modify cancer risk
    Type of Publication: Journal article published
    PubMed ID: 15342448
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  • 2
    Keywords: CANCER ; GROWTH ; GROWTH-FACTOR ; SUPPORT ; COHORT ; cohort study ; POPULATION ; RISK ; GENE ; ASSOCIATION ; POLYMORPHISMS ; SUSCEPTIBILITY ; BREAST ; breast cancer ; BREAST-CANCER ; BRCA1 ; MUTATION ; cancer risk ; GENOTYPES ; BETA ; TGF-BETA-1 ; BRCA2 ; VARIANT ; secretion ; TGF-BETA ; risk modifiers ; GENOTYPE ; USA ; CANCER-RISK ; GENERAL-POPULATION ; CONSORTIUM ; Hereditary cancer ; TRANSFORMING-GROWTH-FACTOR-BETA-1 GENE
    Abstract: Background The transforming growth factor beta-1 gene (TGFB1) is a plausible candidate for breast cancer susceptibility. The L10P variant of TGFB1 is associated with higher circulating levels and secretion of TGF-beta, and recent large-scale studies suggest strongly that this variant is associated with breast cancer risk in the general population. Methods To evaluate whether TGFB1 L10P also modifies the risk of breast cancer in BRCA1 or BRCA2 mutation carriers, we undertook a multi-center study of 3,442 BRCA1 and 2,095 BRCA2 mutation carriers. Results We found no evidence of association between TGFB1 L10P and breast cancer risk in either BRCA1 or BRCA2 mutation carriers. The per-allele HR for the L10P variant was 1.01 (95%CI: 0.92-1.11) in BRCA1 carriers and 0.92 (95%CI: 0.81-1.04) in BRCA2 mutation carriers. Conclusions These results do not support the hypothesis that TGFB1 L10P genotypes modify the risk of breast cancer in BRCA1 or BRCA2 mutation carriers
    Type of Publication: Journal article published
    PubMed ID: 18523885
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  • 3
    Keywords: CANCER ; tumor ; RISK ; TUMORS ; SUFFICIENT ; ASSOCIATION ; chromosome ; FREQUENCY ; polymorphism ; POLYMORPHISMS ; FREQUENCIES ; BREAST ; breast cancer ; BREAST-CANCER ; MOUSE ; NO ; PROGRESSION ; AMPLIFICATION ; HEALTH ; NUMBER ; BRCA1 ; MUTATION ; inactivation ; cancer risk ; MUTATIONS ; ONCOGENE ; CARRIERS ; INDIVIDUALS ; OVEREXPRESSION ; BRCA2 MUTATIONS ; SUSCEPTIBILITY GENE ; ONCOLOGY ; BRCA2 ; ALLELE ; MUTATION CARRIERS ; development ; HOMOZYGOSITY ; biomarker ; INTERVAL ; BREAST-TUMORS ; USA ; cancer research ; CANCER-RISK ; ANEUPLOIDY ; AURORA-A ; TUMOR-DEVELOPMENT ; OOPHORECTOMY ; CHROMOSOME SEGREGATION ; DNA-SEQUENCE VARIANTS ; UNKNOWN CLINICAL-SIGNIFICANCE
    Abstract: The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 311 allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.061. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% Cl, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers
    Type of Publication: Journal article published
    PubMed ID: 17627006
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  • 4
    Keywords: CANCER ; tumor ; CELL ; MODEL ; POPULATION ; RISK ; RISKS ; DISTINCT ; GENES ; SAMPLE ; TUMORS ; FAMILY ; primary ; BIOLOGY ; ASSOCIATION ; polymorphism ; POLYMORPHISMS ; BREAST ; breast cancer ; BREAST-CANCER ; DIFFERENCE ; MUTATION ; genetics ; cancer risk ; MUTATIONS ; HIGH-RISK ; heredity ; CLUSTER ; RE ; BRCA2 ; FAMILIES ; PENETRANCE ; SINGLE NUCLEOTIDE POLYMORPHISMS ; SNPs ; ALLELES ; TECHNOLOGY ; BRCA1 MUTATION CARRIERS ; USA ; CANCER-RISK ; ENGLAND ; GENOME-WIDE ASSOCIATION ; PROPHYLACTIC OOPHORECTOMY ; CONSORTIUM ; FGFR2 ; INVESTIGATORS ; MODIFIERS ; NUCLEOTIDE
    Abstract: Germline mutations in BRCA1 and BRCA2 confer high risks of breast cancer. However, evidence suggests that these risks are modified by other genetic or environmental factors that cluster in families. A recent genome-wide association study has shown that common alleles at single nucleotide polymorphisms (SNPs) in FGFR2 (rs2981582), TNRC9 (rs3803662), and MAP3K1 (rs889312) are associated with increased breast cancer risks in the general population. To investigate whether these loci are also associated with breast cancer risk in BRCA1 and BRCA2 mutation carriers, we genotyped these SNPs in a sample of 10,358 mutation carriers from 23 studies. The minor alleles of SNP rs2981582 and rs889312 were each associated with increased breast cancer risk in BRCA2 mutation carriers (per-allele hazard ratio [HR] = 1.32, 95% CI: 1.20-1.45, p(trend) = 1.7 x 10(-8) and HR = 1.12, 95% CI: 1.02-1.24, P-trend = 0.02) but not in BRCA1 carriers. rs3803662 was associated with increased breast cancer risk in both BRCA1 and BRCA2 mutation carriers (per-allele HR = 1.13, 95% CI: 1.06-1.20, P-trend = 5 x 10(-5) in BRCA1 and BRCA2 combined). These loci appear to interact multiplicatively on breast cancer risk in BRCA2 mutation carriers. The differences in the effects of the FGFR2 and MAP3K1 SNPs between BRCA1 and BRCA2 carriers point to differences in the biology of BRCA1 and BRCA2 breast cancer tumors and confirm the distinct nature of breast cancer in BRCA1 mutation carriers
    Type of Publication: Journal article published
    PubMed ID: 18355772
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