CYP17 genetic polymorphism, breast cancer, and breast cancer risk factors: Australian Breast Cancer Family Study

INTRODUCTION: Because CYP17 can influence the degree of exposure of breast tissues to oestrogen, the interaction between polymorphisms in this gene and hormonal risk factors is of particular interest. We attempted to replicate the findings of studies assessing such interactions with the -34T→C polymorphism. METHODS: Risk factor and CYP17 genotyping data were derived from a large Australian population-based case-control-family study of 1,284 breast cancer cases and 679 controls. Crude and adjusted odds ratio (OR) estimates and 95% confidence intervals (CIs) were calculated by unconditional logistic regression analyses. RESULTS: We found no associations between the CYP17 genotype and breast cancer overall. Premenopausal controls with A(2)/A(2 )genotype had a later age at menarche (P < 0.01). The only associations near statistical significance were that postmenopausal women with A(1)/A(1 )(wild-type) genotype had an increased risk of breast cancer if they had ever used hormone replacement therapy (OR 2.40, 95% CI 1.0 to 5.7; P = 0.05) and if they had menopause after age 47 years (OR 2.59, 95% CI 1.0 to 7.0; P = 0.06). We found no associations in common with any other studies, and no evidence for interactions. CONCLUSION: We observed no evidence of effect modification of reproductive risk factors by CYP17 genotype, although the experiment did not have sufficient statistical power to detect small main effects and modest effects in subgroups. Associations found only in subgroup analyses based on relatively small numbers require cautious interpretation without confirmation by other studies. This emphasizes the need for replication in multiple and large population-based studies to provide convincing evidence for gene–environment interactions

Trends in incidence of treated end-stage renal disease, overall and by primary renal disease, in persons aged 20-64 years in Europe, Canada and the Asia-Pacific region, 1998-2002

AIMS: To determine if rates of diabetic and non-diabetic end-stage renal disease (ESRD), which had been rising in young and middle-aged adults in all populations up to the mid-1990s, had started to decline, and if so, whether improvement had occurred in respect of each of the principal primary renal diseases causing ESRD. METHODS: Poisson regression of age- and sex-standardized incidence of ESRD for persons aged 20-64 years in 18 populations from Europe, Canada and the Asia-Pacific region, for 1998-2002. RESULTS: In persons from 12 European descent (Europid) populations combined, there was a small downward trend in all-cause ESRD (-1.7% per year, P = 0.001), with type 1 diabetic ESRD falling by 7.8% per year (P < 0.001), glomerulonephritic ESRD by 3.1% per year (P = 0.001), and 'all other non-diabetic' ESRD by 2.5% per year (P = 0.02). The reductions in ESRD attributed to hypertensive (-2.2% per year) and polycystic renal disease (-1.5% per year) and unknown diagnosis (-0.2% per year) were not statistically significant. On the other hand, the incidence of type 2 diabetic ESRD rose by 9.9% per year (P < 0.001) in the combined Europid population, although that of (principally type 2) diabetic ESRD remained unchanged in the pooled data from the four non-Europid populations. CONCLUSION: Recent preventive strategies, probably chiefly modern renoprotective treatment, appear to have been effective for tertiary prevention of ESRD caused by the proteinuric nephropathies other than type 2 diabetic nephropathy, for which the continuing increase in Europid populations represents a failure of prevention and/or a change in the nephropathic potential of type 2 diabete