DNA glycosylases involved in base excision repair may be associated with cancer risk in BRCA1 and BRCA2 mutation carriers.

Single Nucleotide Polymorphisms (SNPs) in genes involved in the DNA Base Excision Repair (BER) pathway could be associated with cancer risk in carriers of mutations in the high-penetrance susceptibility genes BRCA1 and BRCA2, given the relation of synthetic lethality that exists between one of the components of the BER pathway, PARP1 (poly ADP ribose polymerase), and both BRCA1 and BRCA2. In the present study, we have performed a comprehensive analysis of 18 genes involved in BER using a tagging SNP approach in a large series of BRCA1 and BRCA2 mutation carriers. 144 SNPs were analyzed in a two stage study involving 23,463 carriers from the CIMBA consortium (the Consortium of Investigators of Modifiers of BRCA1 and BRCA2). Eleven SNPs showed evidence of association with breast and/or ovarian cancer at p<0.05 in the combined analysis. Four of the five genes for which strongest evidence of association was observed were DNA glycosylases. The strongest evidence was for rs1466785 in the NEIL2 (endonuclease VIII-like 2) gene (HR: 1.09, 95% CI (1.03-1.16), p = 2.7 × 10(-3)) for association with breast cancer risk in BRCA2 mutation carriers, and rs2304277 in the OGG1 (8-guanine DNA glycosylase) gene, with ovarian cancer risk in BRCA1 mutation carriers (HR: 1.12 95%CI: 1.03-1.21, p = 4.8 × 10(-3)). DNA glycosylases involved in the first steps of the BER pathway may be associated with cancer risk in BRCA1/2 mutation carriers and should be more comprehensively studied.

Type does matter. Use VIRGIN olive oil as your preferred fat to reduce your risk of breast cancer: case-control EpiGEICAM study.

The Epi-GEICAM study comprises 1017 invasive BC cases matched with controls of similar age (49 ± 9 years) and residence. Diet and OO consumption were collected through a validated food frequency questionnaire. 75% of women referred OO, common (refined) or virgin, as the main fat source. Using conditional logistic regression models, we compared different scenarios of type and frequency of OO consumption, using as reference those women not always using OO for the three culinary practices (seasoning, cooking, and frying) and adding <2 tablespoons (tbsps.) per day during the meal to bread, salad, or dishes. A substantial inverse association was observed in those women always using VOO for the three culinary practices and consuming ≥2 tbsps. of OO per day during meals (adjusted OR, 0.72; 95% CI: 0.51, 1.03; P = 0.07). Potential benefits from OO consumption, at least as regards the protection provided for BC, could be mostly conferred with VOO, and when its consumption is high.

Risk-reduction surgery in BRCA mutation carriers in a Spanish population: adherence and results.

OBJECTIVE: To analyse the level of adherence to prophylactic surgery of breast and/or ovarian cancer in female carriers of the BRCA1 or BRCA2 mutation in a referential genetic counselling unit in Spain. METHODS: Between January 1998 and November 2006, a total of 684 families with several cases of breast and/or ovarian cancer were selected by the Genetic Counselling Unit at the Hospital Clínico Universitario San Carlos. Some of them opted for prophylactic surgery after genetic counselling and genetic testing. RESULTS: The pathogenic mutation was found in 57 families out of a total of 449 families who fulfilled the hereditary breast/ovarian cancer criteria. Out of a total of 238 individuals who were carriers of the mutation, 136 (57%) were offered risk-reducing prophylactic surgery. Prophylactic surgery was chosen by 58 (43%) women out of a total of 136 who were offered this possibility; the histological findings observed 7% malignant lesions in the breast and, in the ovarian-fallopian complex, 2 cases (8%) of a borderline tumour and one case (4%) of papillary adenocarcinoma. CONCLUSION: This is the first study published on the role of prophylactic surgery in BRCA mutation carriers in the Spanish population. The incidence of occult carcinoma in these cases is lower than in other series.