A systematic SNP selection approach to identify mechanisms underlying disease aetiology: Linking height to post-menopausal breast and colorectal cancer risk

Data from GWAS suggest that SNPs associated with complex diseases or traits tend to co-segregate in regions of low recombination, harbouring functionally linked gene clusters. This phenomenon allows for selecting a limited number of SNPs from GWAS repositories for large-scale studies investigating shared mechanisms between diseases. For example, we were interested in shared mechanisms between adult-attained height and post-menopausal breast cancer (BC) and colorectal cancer (CRC) risk, because height is a risk factor for these cancers, though likely not a causal factor. Using SNPs from public GWAS repositories at p-values < 1 × 10-5 and a genomic sliding window of 1 mega base pair, we identified SNP clusters including at least one SNP associated with height and one SNP associated with either post-menopausal BC or CRC risk (or both). SNPs were annotated to genes using HapMap and GRAIL and analysed for significantly overrepresented pathways using ConsensuspathDB. Twelve clusters including 56 SNPs annotated to 26 genes were prioritised because these included at least one height- and one BC risk- or CRC risk-associated SNP annotated to the same gene. Annotated genes were involved in Indian hedgehog signalling (p-value = 7.78 × 10-7) and several cancer site-specific pathways. This systematic approach identified a limited number of clustered SNPs, which pinpoint potential shared mechanisms linking together the complex phenotypes height, post-menopausal BC and CRC

Here today, here tomorrow: Beached timber in Gabon, a persistent threat to nesting sea turtles

notes:types: JOURThe African country of Gabon has seen decadal increases in commercial logging. An unforeseen consequence of this has been that many coastal areas, including several National Parks and Reserves, have suffered severe pollution from beached timber. This has the potential to adversely affect nesting sea turtles, particularly the leatherback turtle (Dermochelys coriacea) for which Gabon constitutes the world’s largest rookery. In this study, we analyse aerial survey data (2003, 2007 and 2011) to determine the temporal persistence and spatial extent of beached timber, and by integrating spatial data on nesting, ascertain regions where beached timber poses the greatest threat to nesting leatherback turtles. There was no marked difference in the number of beached logs recorded across the study area during the period, with 15,160, 13,528 and 17,262 logs recorded in the three years, respectively. There was, however, a significant difference in abundance of beached logs among geographical areas. Analysis highlighted two coastal areas where nesting leatherback turtles were likely to be at greatest risk from beached timber. At one such site, Kingere, within Pongara National Park, where both logs and turtle densities are high, monitoring in 2006/2007 and 2007/2008 suggested that between 1.6% and 4.4% of leatherback turtles could be entrapped at this site. Given the dynamic nature of Gabon’s coastal environment, and the potential limitations of aerial surveys, densities of beached timber could be greater than this analysis reveals. We also propose, that despite recent export restrictions of whole logs, their environmental persistence potentially represents a long-term problem

Dietary folate and folate vitamers and the risk of prostate cancer in The Netherlands Cohort Study

Purpose: The aim of the present study was to examine the association between intake of folate, and specific folate vitamers, and the risk of advanced and total prostate cancer. Methods: The association between dietary folate and prostate cancer risk was evaluated in The Netherlands Cohort Study (NLCS) on diet and cancer, conducted among 58,279 men ages 55-69 years at baseline. Information on diet was collected at baseline by means of food frequency questionnaires. Incident cases were identified by record linkage with regional cancer registries and the Dutch National Database of Pathology Reports. After 17.3 years of follow-up, 3,669 incident prostate cancer cases, of which 1,290 advanced cases, and 2,336 male subcohort members were available for case-cohort analyses. Results: Dietary folate was not associated with prostate cancer risk, nor with the risk of advanced prostate cancer, among men in the NLCS cohort (HR = 1.05, 95 % CI: 0.87-1.26 and HR = 1.09, 95 % CI: 0.88-1.35, respectively, for the highest quintile of folate intake vs. the lowest quintile). Specific folate vitamers were neither associated with the risk of prostate cancer or risk of advanced prostate cancer. Conclusions: Our results do not support an association of dietary folate or specific folate vitamers on the risk of prostate cancer, or advanced prostate cancer. © 2012 Springer Science+Business Media Dordrecht