International journal of cancer. Journal international du cancer
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Multicenter Study Comparative Study
Comprehensive analysis of 989 patients with breast or ovarian cancer provides BRCA1 and BRCA2 mutation profiles and frequencies for the German population.
The main focus of this German-wide multi-center study was to establish a BRCA1/2 mutation profile and to determine family types with high frequencies of mutations in these genes. In a comprehensive study, the entire coding sequences of the breast cancer genes BRCA1 and BRCA2 were analyzed in 989 unrelated patients from German breast/ovarian cancer families. A total of 77 BRCA1 and 63 BRCA2 distinct deleterious mutations were found in 302 patients. ⋯ These data provide strong evidence for further predisposing genes in the German population. In breast cancer families with 2 or 3 affected females but only a single or no premenopausal case, mutations were detected with low frequencies (about 10% or less for both genes). The decision for or against molecular diagnosis is now aided by considering the expected mutation detection rates that greatly depend on family history and structure.
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There is suggestive evidence that the use of wood for cooking increases the risk of invasive cervical cancer. We investigated this association in women with cervical neoplasia in Honduras. Women aged 20-64 years with cervical intraepithelial neoplasia (CIN) grade I (n = 44), CIN II (n = 36) or CIN III (n = 45) were recruited from screening programs in Tegucigalpa City and each was matched by age and clinic to 2 controls (241 total) without cervical abnormalities. ⋯ This association was independent of other risk factors including education, parity and number of sexual partners. ORs in the final model were 0.37 for age at first intercourse 20 years or higher and 5.69 for more than 35 years of exposure to wood burning in the kitchen. The present study suggests that the use of wood for cooking is a risk factor for cervical neoplasia that deserves further study, given its high prevalence in developing countries.
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Comparative Study
Association between BRCA1 and BRCA2 mutations and cancer phenotype in Spanish breast/ovarian cancer families: implications for genetic testing.
Index cases from a clinically relevant cohort of 102 Spanish families with at least 3 cases of breast and/or ovarian cancer (at least 1 case diagnosed before age 50) in the same lineage were screened for germline mutations in the entire coding sequence and intron boundaries of the breast cancer susceptibility genes BRCA1 and BRCA2. Overall, the prevalence of mutations was 43% in female breast/ovarian cancer families, 15% in female breast cancer families and 100% in male breast cancer families. Three recurrent mutations (185delAG, 589delCT and A1708E) explained 63% of BRCA1-related families. ⋯ We have developed a logistic regression model for predicting the probability of harbouring a mutation in either BRCA1 or BRCA2 as a function of the cancer phenotype present in the family. The predictive positive and negative values of this model were 77.4% and 79%, respectively (probability cutoff of 30%). The findings of our work may be a useful tool for increasing the cost-effectiveness of genetic testing in familial cancer clinics.