RESUMEN
BACKGROUND: XRCC2 participates in homologous recombination and in DNA repair. XRCC2 has been reported to be a breast cancer susceptibility gene and is now included in several breast cancer susceptibility gene panels. METHODS: We sequenced XRCC2 in 617 Polish women with familial breast cancer and found a founder mutation. We then genotyped 12,617 women with breast cancer and 4599 controls for the XRCC2 founder mutation. RESULTS: We identified a recurrent truncating mutation of XRCC2 (c.96delT, p.Phe32fs) in 3 of 617 patients with familial breast cancer who were sequenced. The c.96delT mutation was then detected in 29 of 12,617 unselected breast cancer cases (0.23%) compared to 11 of 4599 cancer-free women (0.24%) (OR = 0.96; 95% CI 0.48-1.93). The mutation frequency in 1988 women with familial breast cancer was 0.2% (OR = 0.84, 95% CI 0.27-2.65). Breast cancers in XRCC2 mutation carriers and non-carriers were similar with respect to age of diagnosis and clinical characteristics. Loss of the wild-type XRCC2 allele was observed only in one of the eight breast cancers from patients who carried the XRCC2 mutation. No cancer type was more common in first- or second-degree relatives of XRCC2 mutation carriers than in relatives of the non-carriers. CONCLUSION: XRCC2 c.96delT is a protein-truncating founder variant in Poland. There is no evidence that this mutation predisposes to breast cancer (and other cancers). It is premature to consider XRCC2 as a breast cancer-predisposing gene.
Asunto(s)
Neoplasias de la Mama/genética , Proteínas de Unión al ADN/genética , Adulto , Anciano , Alelos , Neoplasias de la Mama/epidemiología , Neoplasias de la Mama/patología , Femenino , Estudios de Asociación Genética , Pruebas Genéticas , Genotipo , Humanos , Persona de Mediana Edad , Mutación , Tasa de Mutación , Polonia/epidemiologíaRESUMEN
AIM: To determine whether three of CYP1B1 single nucleotide polymorphisms, c.142C > G, c.355G > T and c.1294C > G are associated with a lung cancer risk. PATIENTS & METHODS: A total of 112 lung cancer patients and 100 controls were genotyped using the RFLP-PCR. RESULTS: In the c.142C > G polymorphisms, G allele was more frequent in lung cancer patients than in controls (p < 0.001), while in the c.1294C > G polymorphisms, C allele was more frequent in lung cancer patients, than in controls (p = 0.012). In the c.355G > T polymorphism, the distribution of alleles in both analyzed groups was similar. The GTC haplotype turned out to be correlated with the increased lung cancer risk, compared with the most common CGG haplotype (OR: 2.38; p = 0.001). CONCLUSION: CYP1B1 gene polymorphisms appear to influence lung cancer susceptibility.
Asunto(s)
Citocromo P-450 CYP1B1/genética , Neoplasias Pulmonares/genética , Polimorfismo de Nucleótido Simple , Fumadores , Anciano , Anciano de 80 o más Años , Estudios de Casos y Controles , Femenino , Frecuencia de los Genes , Predisposición Genética a la Enfermedad , Haplotipos , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , PoloniaRESUMEN
Bloom Syndrome is a rare recessive disease which includes a susceptibility to various cancers. It is caused by homozygous mutations of the BLM gene. To investigate whether heterozygous carriers of a BLM mutation are predisposed to breast cancer, we sequenced BLM in 617 patients from Polish families with a strong family history of breast cancer. We detected a founder mutation (c.1642C>T, p.Gln548Ter) in 3 of the 617 breast cancer patients (0.49%) who were sequenced. Then, we genotyped 14,804 unselected breast cancer cases and 4698 cancer-free women for the founder mutation. It was identified in 82 of 14,804 (0.55%) unselected cases and in 26 of 4698 (0.55%) controls (OR = 1.0; 95%CI 0.6-1.6). Clinical characteristics of breast cancers in the BLM mutation carriers and non-carriers were similar. Loss of the wild-type BLM allele was not detected in cancers from the BLM mutation carriers. No cancer type was more common in the relatives of mutation carriers compared to relatives of non-carriers. The BLM founder mutation p.Gln548Ter, which in a homozygous state is a cause of Bloom syndrome, does not appear to predispose to breast cancer in a heterozygous state. The finding casts doubt on the designation of BLM as an autosomal dominant breast cancer susceptibility gene.