title: Genetic polymorphims of estrogen receptor alpha -397 PvuII (T>C) and -351 XbaI (A>G) in a portuguese population: prevalence and relation with breast cancer susceptibility.
abstract: Estrogen receptor alpha (ERα), that mediates the biologic effects of estrogen in estrogen-sensitive tissues like breast, is genetically polymorphic. To evaluate the association between -397 PvuII (T>C) and -351 XbaI (A>G) restriction fragment length polymorphisms (RFLPs) in intron 1 of ERα gene and susceptibility of breast cancer, we undertook a case-control study in BRCA1 185delAG and 5382insC/BRCA2 6174delT negative Portuguese women. The study population consisted of 107 patients with histological diagnosis of breast cancer and 121 women with no history of breast cancer. Genomic DNA was extracted from blood samples and genotyping analyses were performed by PCR-RFLP. XbaI polymorphism was associated with a significant reduced risk of breast cancer for carriers of the x allele in homozygozity (OR 0.178; 95% CI 0.070-0.456; P<0.001) or heterozigozity (OR 0.223; 95% CI 0.089-0.561; P=0.001). The PvuII polymorphism was associated with a non-significantly reduced risk. The combined analysis of PvuII and XbaI polymorphisms revealed none synergistic effect of the two genotypes, except for simultaneous carriers of pp and xx genotypes, that have a reduced risk of breast cancer (OR 0.226; 95% CI 0.049-1.035; P=0.044). The combination of PvuII and XbaI genotypes into haplotypes showed that carriers of two copies of the px (ppxx) haplotype had a reduced risk of breast cancer (OR 0.405; 95% CI 0.194-0.843; P=0.014), compared with PX (PPXX+PPXx+PpXX+PpXx) haplotypes. PvuII and XbaI polymorphisms were in linkage disequilibrium both in cases (D=0.044, r2=0.049, X2=5.216, P=0.022) and controls (D=0.090, r2=0.139, X2=16.819, P<0.001), but not in the entire sample population analyzed as a whole (D=0.087, r2=0.0076, X2=1.733, P=0.188). In conclusion, in this case-control study we found that ERα gene XbaI polymorphism may modify individual susceptibility for breast cancer in this population.
authors.affiliation: CICS-UBI-Centro de Investigação em Ciências da Saúde, Universidade da Beira Interio, Avenida Infante D. Henrique, 6200-506, Covilhã, Portugal. cramalhinho@fcsaude.ubi.pt
authors.forename: A C
authors.initials: AC
authors.lastname: Ramalhinho
authors.forename: J
authors.initials: J
authors.lastname: Marques
authors.forename: J A
authors.initials: JA
authors.lastname: Fonseca-Moutinho
authors.forename: L
authors.initials: L
authors.lastname: Breitenfeld
mesh_terms: D001943:Breast Neoplasms / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D017931:DNA Primers / Q000235:genetics; D047628:Estrogen Receptor alpha / Q000235:genetics*; D005260:Female; D019398:Genes, BRCA1; D024522:Genes, BRCA2; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D005838:Genotype; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D054643:INDEL Mutation / Q000235:genetics; D016013:Likelihood Functions; D015810:Linkage Disequilibrium; D016017:Odds Ratio; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011174:Portugal / Q000453:epidemiology
chemical_list: D017931:DNA Primers; C506487:ESR1 protein, human; D047628:Estrogen Receptor alpha