title: Breast cancer risk and polymorphisms in genes involved in metabolism of estrogens (CYP17, HSD17beta1, COMT and MnSOD): possible protective role of MnSOD gene polymorphism Val/Ala and Ala/Ala in women that never breast fed.
abstract: Polymorphisms in genes encoding enzymes involved in estrogen metabolism are held to be candidates for associations with breast disease, since there is evidence that circulating estrogens are associated with breast cancer risk. In this study, we evaluated the frequency of different polymorphisms related with estrogen metabolism [COMT Val158Met, CYP17 (5'UTR, T27C); HSD17beta1 Gly313Ser and MnSOD Val16Ala] in a breast cancer resistant population, the Xavante Indians, and the frequencies were compared with the ones reported in other populations where breast cancer case-control studies dealing with these polymorphisms have been carried out. The data obtained showed that, apart from the MnSOD Val16Ala polymorphism where the frequency of the variant allele was much higher than that reported in other populations, all the others were within the range reported in other populations. Considering these data we carried out a case-control study in the Portuguese population (241 cases and 457 controls) in order to evaluate the potential role of this polymorphism in breast cancer susceptibility. The results obtained did not reveal a significant association between individual genotypes and breast cancer risk. However, when the population was stratified for breast feeding, it was observed that for the patients that never breast fed the presence of the variant allele (Ala) was marginally associated with a decreased risk for this pathology (adjusted OR: 0.575 (0.327-1.011). These data seem to suggest that individuals who never breast fed with MnSOD Val16Ala variant allele are at a lower risk for breast cancer, but larger studies are required to confirm these results.
authors.affiliation: Faculty of Medical Sciences, Department of Genetics, New University of Lisbon, Lisboa, Portugal.
authors.forename: Susana N
authors.initials: SN
authors.lastname: Silva
authors.forename: Marisa N
authors.initials: MN
authors.lastname: Cabral
authors.forename: Guilherme
authors.initials: G
authors.lastname: Bezerra de Castro
authors.forename: Marcelo
authors.initials: M
authors.lastname: Pires
authors.forename: Ana Paula
authors.initials: AP
authors.lastname: Azevedo
authors.forename: Isabel
authors.initials: I
authors.lastname: Manita
authors.forename: Julieta Esperança
authors.initials: JE
authors.lastname: Pina
authors.forename: José
authors.initials: J
authors.lastname: Rueff
authors.forename: Jorge
authors.initials: J
authors.lastname: Gaspar
mesh_terms: D000409:Alanine / Q000737:chemistry; D001942:Breast Feeding; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000096:biosynthesis*; D004960:Estradiol Dehydrogenases / Q000096:biosynthesis*; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D006801:Humans; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012306:Risk; D013254:Steroid 17-alpha-Hydroxylase / Q000096:biosynthesis*; D013482:Superoxide Dismutase / Q000096:biosynthesis* / Q000235:genetics*; D014633:Valine / Q000737:chemistry
chemical_list: D004967:Estrogens; D004960:Estradiol Dehydrogenases; C513331:HSD17B1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D013482:Superoxide Dismutase; D002394:Catechol O-Methyltransferase; D014633:Valine; D000409:Alanine