title: Methyl group metabolism gene polymorphisms as modifier of breast cancer risk in Italian BRCA1/2 carriers.
abstract: BRCA1 and 2 are major cancer susceptibility genes but their penetrance is highly variable. The folate metabolism plays an important role in DNA methylation and its alterated metabolism is associated with cancer risk. The role of allele variants 677T and 1298C (MTHFR gene) and 2756G (MS gene) has been investigated as potentially modifying factors of BRCA gene penetrance, evaluated as age at first diagnosis of cancer, in 484 BRCA1/BRCA2 carriers and in 108 sporadic breast cancer cases as a control group. The genotype analysis has been performed by means of PCR/RFLP's. The analysis of association between a particular genotype and disease risk was performed using Cox Regression with time to breast or ovarian cancer onset as the end-point. The presence of 677T allele confers an increased risk of breast cancer in BRCA1 carriers (P = 0.007) and the presence of 1298C allele confers an increased risk of breast cancer in sporadic cases (P = 0.015).
authors.affiliation: Section of Oncogenetics, Division of Pathology, Department of Oncology, University of Pisa, Via Roma, 57, PI,, I-56126 Pisa, Italy.
authors.forename: C
authors.initials: C
authors.lastname: Pepe
authors.forename: L
authors.initials: L
authors.lastname: Guidugli
authors.forename: E
authors.initials: E
authors.lastname: Sensi
authors.forename: P
authors.initials: P
authors.lastname: Aretini
authors.forename: E
authors.initials: E
authors.lastname: D'Andrea
authors.forename: M
authors.initials: M
authors.lastname: Montagna
authors.forename: S
authors.initials: S
authors.lastname: Manoukian
authors.forename: L
authors.initials: L
authors.lastname: Ottini
authors.forename: P
authors.initials: P
authors.lastname: Radice
authors.forename: A
authors.initials: A
authors.lastname: Viel
authors.forename: G
authors.initials: G
authors.lastname: Bevilacqua
authors.forename: M A
authors.initials: MA
authors.lastname: Caligo
mesh_terms: D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase / Q000235:genetics*; D000328:Adult; D001943:Breast Neoplasms / Q000453:epidemiology / Q000235:genetics*; D016022:Case-Control Studies; D019175:DNA Methylation; D005260:Female; D005787:Gene Frequency; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease / Q000453:epidemiology / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D008875:Middle Aged; D009378:Neoplasms, Multiple Primary / Q000453:epidemiology / Q000235:genetics; D010051:Ovarian Neoplasms / Q000453:epidemiology / Q000235:genetics; D019683:Penetrance; D012150:Polymorphism, Restriction Fragment Length; D016016:Proportional Hazards Models; D012306:Risk
chemical_list: D042965:Methylenetetrahydrofolate Reductase (NADPH2); D013766:5-Methyltetrahydrofolate-Homocysteine S-Methyltransferase