CHEK2 variant I157T may be associated with increased breast cancer risk

Cell cycle checkpoint kinase 2 (CHEK2) is a transducer of cellular responses to DNA damage. The CHEK2 1100delC has previously been shown to be a low-penetrance breast cancer susceptibility allele. We have evaluated the role of another CHEK2 variant, I157T in the FHA domain of the gene, for association with breast cancer. I157T was found at a significantly higher frequency in the population-based series of breast cancer patients (77/1035, 7.4%, odds ratio [OR] = 1.43, 95% confidence interval [CI] = 1.06-1.95, p = 0.021) than among population controls (100/1885, 5.3%). The frequency in the familial breast cancer patients was not elevated (28/507, 5.5%, OR = 1.04, 95% CI = 0.68-1.61). The I157T protein, that undermines cellular responses to ionizing radiation and shows deficiency in substrate recognition in vivo, was expressed at normal level in tumor tissues as well as in cultured cells. The I157T protein was stable and it dimerized with the wild-type CHEK2 co-expressed in human cells. These functional properties of the I157T protein suggest that this variant may have negative effect on the pool of normal CHEK2 protein in heterozygous carrier cells by formation of heterodimers with wild-type CHEK2. The I157T variant may be associated with breast cancer risk, but the risk is lower than for 1100delC.     

Trial of labor after cesarean delivery with a lower-segment, vertical uterine incision: Is it safe?

Objective: Our purpose was to assess maternal and perinatal outcomes associated with a trial of labor and attempted vaginal birth after prior low-segment vertical cesarian delivery.Study design: During a 10-year period in a single tertiary hospital, all patients with a prior low-segment uterine incision (whether vertical or transverse) were considered candidates for a trial of labor in the absence of other contraindications or patient refusal. Among the 1137 women who underwent low-segment vertial cesarean delivery, 262 were subsequently delivered of 322 live-born infants, and 174 (54%) of them were identified retrospectively as having attempted vaginal birth. The maternal and perinatal outcomes of patients who did or did not undergo a trial of labor were analyzed and compared.Results: No significant differences between the two patient groups were observed regarding demographic characteristics, antepartum complications, gestational age at delivery (mean 37.4 weeks), birth weight, and cord pH at delivery. Vaginal delivery was accomplished successfully in 144 of 174 (83%) patients who underwent a trial of labor. Abdominal delivery was necessary for 17 mothers with labor disorders and 13 with suspected fetal distress. Postpartum hemorrhage occurred more often in the trial of labor group (7/174 [4.0%] vs 2/148 [1.4%], p not significant), but endometritis developed significantly more often in patients with elective repeat cesarean delivery (16.9% vs 6.3%, p - 0.006)/ Rupture of the low-segment vertical cesarean group scar occurred in 2 patients during a trial of labor (1.1%) versus none in the elective repeat cesarean group. Neither mother experienced fetal extrusion or adverse maternal or fetal sequelae. Frequency of serious neonatal complications (8.1% vs 10%) and neonatal mortality (1.7% vs 2.0%) were similar between groups. All neonatal deaths were a result of extreme prematurity or congenital anomalies.Conclusions: Our experience indicates that a mother with a prior low-segment vertical cesarean delivery can undertake a trial of labor with relative maternal-perinata safety. The likelihood of successful outcome and the incidence of complications are comparable to those of published experience with a trial of labor after a previous low-segment transverse incision.     

Comparison of cancer registry and clinical data as predictors for breast cancer survival

Background  In spite of the increasing amount of clinically relevant information for survival from breast cancer, the amount of data recorded in a population-based cancer registry is limited and the registry-based survival predictions are routinely made without clinical details. Objective  To find out how important is the role of screening and clinical tumor characteristics in addition to cancer registry information in describing the breast cancer survival. Methods  A representative clinical database on 483 breast cancer patients diagnosed during 1996–1997 in Tampere University Hospital Area was linked with Finnish Cancer Registry data and a survival model including the available registry variables was compared to models including screen-detection information and clinical tumor characteristics also. Results and conclusion  Estimates of registry stage and age act as surrogates for clinical variables and mammography-detection. The surrogacy was found to be almost complete indicating that clinical variables are not necessarily needed when making breast cancer mortality predictions based on a population-based cancer registry. In cases with dissimilar staging cancer registry stage gave a better picture of the breast cancer survival than the clinical stage. This work was performed in Finnish Cancer Registry, Helsinki, Finland.