Maternal outcomes in subsequent delivery after previous obstetric anal sphincter injury (OASI): a multi-centre retrospective cohort study.

INTRODUCTION AND HYPOTHESIS: Women with a history of obstetric anal sphincter injury (OASI) are at increased risk of recurrence (rOASI) at subsequent delivery; however, evidence regarding the factors influencing this risk is limited. Furthermore, little is known about what factors influence the decision to alternatively deliver by elective caesarean section (ELLSCS). METHODS: Retrospective univariate and multivariate logistic regression analysis of prospectively collected data from four NHS electronic maternity databases including primiparous women sustaining OASIS during a singleton, term, cephalic, vaginal delivery between 2004 and 2015, who had a subsequent delivery. RESULTS: Two thousand two hundred seventy-two women met the criteria; 10.2% delivering vaginally had a repeat OASI and 59.4% had a second-degree tear. Women having an ELLSCS were more likely to be Caucasian, older, have previously had an operative vaginal delivery (OVD) and have a more severe degree of OASI. Positive predictors for rOASI were increased birth weight and maternal age at both index and subsequent deliveries, a more severe degree of initial OASI and Asian ethnicity. The overall mediolateral episiotomy (MLE) rate was 15.6%; 77.2% of those who had an episiotomy sustained no spontaneous perineal trauma. Only 4.4% of women with a rOASI had an MLE, whilst the MLE rate was 16.9% in those without a recurrence (p < 0.001). MLE decreased the risk of rOASI by 80%. Birth weight > 4 kg increased the risk 2.5 fold. CONCLUSIONS: Women with previous OASIS are at an increased risk of recurrence. A more liberal use of MLE during subsequent vaginal delivery could significantly reduce the risk of recurrence.

Association of the progesterone receptor gene with breast cancer risk: a single-nucleotide polymorphism tagging approach.

Association studies on susceptibility to breast cancer using single nucleotide polymorphisms (SNP) in the progesterone receptor (PGR) gene have been previously published, but the results have been inconclusive. We used a comprehensive SNP-tagging approach to search for low-penetrance susceptibility alleles in a study of up to 4,647 cases and 4,564 controls, in a two-stage study design. We identified seven tagging SNPs using genotype data from the National Institute of Environmental Health Sciences (NIEHS) Environmental Genome Project and typed these, and an additional three SNPs, in 2,345 breast cancer cases and 2,284 controls (set 1). Three SNPs showed no evidence for association and were not studied further, whereas seven SNPs (rs11571171, rs7116336, rs660149, rs10895068, rs500760, rs566351, and rs1042838) exhibited significant associations at P < 0.1 using either a heterogeneity or trend test and progressed to be genotyped in set 2. After both stages, only one SNP was significantly associated with an increased risk of breast cancer - the PGR-12 (rs1042638) V660L valine to leucine polymorphism [VL heterozygotes (odds ratio, 1.13; 95% confidence interval, 1.03-1.24) and the LL homozygotes (odds ratio, 1.30; 95% confidence interval, 0.98-1.73), P(het) = 0.008, P(trend) = 0.002]. Similar estimates were obtained in a combined analysis of our data with those from three other published studies. We conclude that the 660L allele may be associated with a moderately increased risk of breast cancer, but that other common SNPs in the PGR gene are unlikely to be associated with a substantial risk of breast cancer.

Allelic association of the human homologue of the mouse modifier Ptprj with breast cancer.

Human homologues of mouse cancer modifier genes may play a role in cancer risk and prognosis. A proportion of the familial risk of common cancers may be attributable to variants in such genes, each contributing to a small effect. The protein tyrosine phosphatase receptor type J (PTPRJ) has been recently identified as being the protein encoded by the Scc1 mouse gene (susceptibility to colon cancer-1). In addition, the PTPRJ gene has been shown to be somatically altered in several human cancer types such as colon, lung and breast cancers and to have the characteristics of a tumour-suppressor gene. The purpose of this study was to determine whether common variants in the PTPRJ gene represent low penetrance breast cancer susceptibility alleles. To test this hypothesis, we assessed single nucleotide polymorphisms (SNPs) tagging the common SNPs and haplotypes of the gene in 4512 cases and 4554 controls from the East Anglian population. We observed a difference in the haplotype frequency distributions between cases and controls (P = 0.0023, OR = 0.81 [0.72-0.92]). Thus, carrying a specific PTPRJ haplotype confers a protective effect on the risk of breast cancer. This result establishes the principle that mouse cancer modifier genes are candidates for low penetrance human breast cancer susceptibility genes.