CYP1B1 and predisposition to breast cancer in Poland.

BACKGROUND: The CYP1B1 gene is a polymorphic member of the P450 gene family and is considered to be a candidate gene for cancers of various types. OBJECTIVE: We inquired whether four SNPs in the CYP1B1 gene, alone or in combination, might be associated with breast cancer risk in Poland. METHODS: We genotyped 2017 cases of breast cancer and 876 controls, for four SNPs in the CYP1B1 gene. Genotype and haplotype frequencies were compared in cases and controls. RESULTS: In combinations of the R48G, A119S and L432V SNPs, four of the eight CYP1B1 haplotypes were more common in controls than in cases and each of these appeared to have a significant protective effect. A large reduction in risk was observed for women who were homozygous for one of these four haplotypes (OR = 0.2; 95%; CI = 0.05-0.5; P = 0.001) compared to women who were homozygous for the most common haplotype. In contrast, women who were homozygous for the GTC haplotype were at increased risk (OR = 1.5; 95%; CI = 1.0-2.1; P = 0.03) compared to women with the most common haplotype. CONCLUSIONS: The CYP1B1 gene appears to influence breast cancer susceptibility in Poland.

A high proportion of founder BRCA1 mutations in Polish breast cancer families.

Three mutations in BRCA1 (5382insC, C61G and 4153delA) are common in Poland and account for the majority of mutations identified to date in Polish breast and breast-ovarian cancer families. It is not known, however, to what extent these 3 founder mutations account for all of the BRCA mutations distributed throughout the country. This question has important implications for health policy and the design of epidemiologic studies. To establish the relative contributions of founder and nonfounder BRCA mutations, we established the entire spectrum of BRCA1 and BRCA2 mutations in a large set of breast-ovarian cancer families with origins in all regions of Poland. We sequenced the entire coding regions of the BRCA1 and BRCA2 genes in 100 Polish families with 3 or more cases of breast cancer and in 100 families with cases of both breast and ovarian cancer. A mutation in BRCA1 or BRCA2 was detected in 66% of breast cancer families and in 63% of breast-ovarian cancer families. Of 129 mutations, 122 (94.6%) were in BRCA1 and 7 (5.4%) were in BRCA2. Of the 122 families with BRCA1 mutations, 119 (97.5%) had a recurrent mutation (i.e., one that was seen in at least 2 families). In particular, 111 families (91.0%) carried one of the 3 common founder mutations. The mutation spectrum was not different between families with and without ovarian cancer. These findings suggest that a rapid and inexpensive assay directed at identifying the 3 common founder mutations will have a sensitivity of 86% compared to a much more costly and labor-intensive full-sequence analysis of both genes. This rapid test will facilitate large-scale national epidemiologic and clinical studies of hereditary breast cancer, potentially including studies of chemoprevention.