16 research outputs found
Uninterrupted oral anticoagulation versus bridging in patients with long-term oral anticoagulation during percutaneous coronary intervention: subgroup analysis from the WOEST trial
Searching for the Best: Stochastic Approximation, Simulated Annealing and Related Procedures
Methyl group metabolism gene polymorphisms as modifier of breast cancer risk in Italian BRCA1/2 carriers
BRCA1 and 2 are major cancer susceptibility genes but their penetrance is highly variable. The folate metabolism plays an important role in DNA methylation and its alterated metabolism is associated with cancer risk. The role of allele variants 677T and 1298C (MTHFR gene) and 2756G (MS gene) has been investigated as potentially modifying factors of BRCA gene penetrance, evaluated as age at first diagnosis of cancer, in 484 BRCA1/BRCA2 carriers and in 108 sporadic breast cancer cases as a control group. The genotype analysis has been performed by means of PCR/RFLP's. The analysis of association between a particular genotype and disease risk was performed using Cox Regression with time to breast or ovarian cancer onset as the end-point. The presence of 677T allele confers an increased risk of breast cancer in BRCA1 carriers (P = 0.007) and the presence of 1298C allele confers an increased risk of breast cancer in sporadic cases (P = 0.015). © 2006 Springer Science+Business Media B.V
Performance of simultaneous multi-slice accelerated diffusion-weighted imaging for assessing focal renal lesions in pediatric patients with tuberous sclerosis complex
Imaging for Screening and Surveillance of Patients with Hereditary Forms of Renal Cell Carcinoma
BRCA2 Polymorphic stop codon K3326X and the risk of breast, prostate, and ovarian cancers
Q1Q1ArtĂculo Original1-10Background: The K3326X variant in BRCA2 (BRCA2*c.9976A>T; p.Lys3326*; rs11571833) has been found to be associated with
small increased risks of breast cancer. However, it is not clear to what extent linkage disequilibrium with fully pathogenic
mutations might account for this association. There is scant information about the effect of K3326X in other hormonerelated cancers.
Methods: Using weighted logistic regression, we analyzed data from the large iCOGS study including 76 637 cancer case
patients and 83 796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant
carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a
pathogenic BRCA2 variant. Using Cox proportional hazards modeling, we also examined the associations of K3326X with
breast and ovarian cancer risks among 7183 BRCA1 variant carriers. All statistical tests were two-sided.
Results: The K3326X variant was associated with breast (ORw = 1.28, 95% CI = 1.17 to 1.40, P = 5.9x10-6) and invasive ovarian
cancer (ORw = 1.26, 95% CI = 1.10 to 1.43, P = 3.8x10-3). These associations were stronger for serous ovarian cancer and for
estrogen receptorânegative breast cancer (ORw = 1.46, 95% CI = 1.2 to 1.70, P = 3.4x10-5 and ORw = 1.50, 95% CI = 1.28 to 1.76,
P = 4.1x10-5, respectively). For BRCA1 mutation carriers, there was a statistically significant inverse association of the K3326X
variant with risk of ovarian cancer (HR = 0.43, 95% CI = 0.22 to 0.84, P = .013) but no association with breast cancer. No
association with prostate cancer was observed.
Conclusions: Our study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian
cancers independent of other pathogenic variants in BRCA2. Further studies are needed to determine the biological
mechanism of action responsible for these associations