The AIB1 polyglutamine repeat does not modify breast cancer risk in BRCA1 and BRCA2 mutation carriers.

This is by far the largest study of its kind to date, and further suggests that AIB1 does not play a substantial role in modifying the phenotype of BRCA1 and BRCA2 carriers. The AIB1 gene encodes the AIB1/SRC-3 steroid hormone receptor coactivator, and amplification of the gene and/or protein occurs in breast and ovarian tumors. A CAG/CAA repeat length polymorphism encodes a stretch of 17 to 29 glutamines in the HR-interacting carboxyl-terminal region of the protein which is somatically unstable in tumor tissues and cell lines. There is conflicting evidence regarding the role of this polymorphism as a modifier of breast cancer risk in BRCA1 and BRCA2 carriers. To further evaluate the evidence for an association between AIB1 glutamine repeat length and breast cancer risk in BRCA1 and BRCA2 mutation carriers, we have genotyped this polymorphism in 1,090 BRCA1 and 661 BRCA2 mutation carriers from Australia, Europe, and North America. There was no evidence for an increased risk associated with AIB1 glutamine repeat length. Given the large sample size, with more than adequate power to detect previously reported effects, we conclude that the AIB1 glutamine repeat does not substantially modify risk of breast cancer in BRCA1 and BRCA2 mutation carriers.

How effective is penetrating corneal transplantation? Factors influencing long-term outcome in multivariate analysis.

BACKGROUND: In a large patient cohort, we investigated long-term corneal graft outcome, risk factors for graft failure, and whether corneal graft survival had improved over time. METHODS: Records of 10,952 full-thickness corneal grafts with associated archival follow-up were examined within a prospectively-maintained, national database of 13,831 records, with follow-up extending for up to 18 years. Kaplan-Meier survival analysis was used to indicate variables of interest for Cox proportional hazards regression analysis. A model clustered by individual patient to control for inter-eye or inter-graft dependence was constructed to identify variables best predicting penetrating corneal graft failure. RESULTS: Probability of corneal graft survival was 0.86 at 1 year, 0.73 at 5 years, 0.62 at 10 years, and 0.55 at 15 years. Graft survival did not improve over a 15-year timeframe. Variables predicting graft failure in multivariate analysis included transplant centre, donor age, preoperative diagnosis, number of previous ipsilateral grafts, lens status, history of corneal neovascularisation, ocular inflammation or raised intraocular pressure in the grafted eye, requirement for anterior vitrectomy, graft size, early suture removal, postoperative events including graft neovascularisation, rise in intraocular pressure, and rejection episodes, type of treatment for raised intraocular pressure, and arrangements for recipient follow-up. A further 11 variables showing a significant influence on graft survival in univariate analysis were not included in the final Cox model. CONCLUSION: The long-term results of corneal transplantation are no better than for other forms of transplantation and have shown no measurable improvement over the past 15 years.