ABSTRACT
The 1100delC mutation of the cell cycle checkpoint kinase 2 (CHEK2) gene confers an increased risk for breast cancer, but the clinical impact of other CHEK2 gene variants remains unclear. We determined the frequency of two functionally relevant CHEK2 gene mutations, I157T and IVS2+1G > A, in two large series of breast cancer cases and controls from two independent populations. Our first series consisted of a hospital-based cohort of 996 German breast cancer cases and 486 population controls, and the second series consisted of 424 breast cancer patients and 307 population controls from the Republic of Belarus. The missense substitution I157T was identified in 22/996 cases (2.2%) vs. 3/486 controls (0.6%; OR = 3.6, 95% CI 1.1-12.2, p = 0.044) in the German population and in 24/424 cases (5.7%) vs. 4/307 controls (1.3%; OR = 4.5, 95% CI 1.6-13.2, p = 0.005) in the Byelorussian cohorts. The splicing mutation IVS2+1G > A was infrequent in both populations, being observed in 3/996 German and 4/424 Byelorussian patients (0.3% and 0.9%, respectively) and in 1/486 German controls (0.2%; adjusted OR = 4.0, 95% CI 0.5-30.8, p = 0.273). Heterozygous CHEK2 mutation carriers tended to be diagnosed at an earlier age in both populations, but these differences did not reach statistical significance. Family history of breast cancer did not differ between carriers and noncarriers. Our data indicate that the I157T allele, and possibly the IVS2+1G > A allele, of the CHEK2 gene contribute to inherited breast cancer susceptibility.
Subject(s)
Breast Neoplasms/genetics , Genetic Predisposition to Disease , Protein Serine-Threonine Kinases/genetics , Adult , Age of Onset , Breast Neoplasms/epidemiology , Breast Neoplasms/pathology , Case-Control Studies , Cell Cycle , Checkpoint Kinase 2 , DNA Mutational Analysis , Female , Germany/epidemiology , Heterozygote , Humans , Incidence , Middle Aged , Mutation, Missense , Odds Ratio , Pedigree , Republic of Belarus/epidemiologyABSTRACT
Evaluation of the effects of radioactive contamination on human populations is important for an understanding of the present and future risk for human health, including the genetic risk. This review centers on the results of population monitoring of developmental anomalies among human embryos and congenital malformations among newborn in the Republic of Belarus before and after Chemobyl accident. The data revealed that the incidences of developmental anomalies and congenital malformation from the mostly radionuclide-contaminated rural regions of Belarus reliably exceed the indices in control areas.
