English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Zendy Open

Presents the pdf analysis as premium feature

PDF Analysis

Insights

Presents the summarisation as premium feature

Summarisation

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the zaia usage as premium feature

ZAIA

Zendy Tools

Zendy Plus

Presents the access of premium content as premium feature

Premium Content

Common variants in the hepatocyte nuclear factor 1 homeobox B ( HNF1B ) gene are associated with the risk of Type II diabetes and multiple cancers. Evidence to date indicates that cancer risk may be mediated via genetic or epigenetic effects on  HNF1B  gene expression. We previously found single-nucleotide polymorphisms (SNPs) at the  HNF1B  locus to be associated with endometrial cancer, and now report extensive fine-mapping and  in silico  and laboratory analyses of this locus. Analysis of 1184 genotyped and imputed SNPs in 6608 Caucasian cases and 37 925 controls, and 895 Asian cases and 1968 controls, revealed the best signal of association for SNP rs11263763 ( P  = 8.4 × 10 −14 , odds ratio = 0.86, 95% confidence interval = 0.82–0.89), located within  HNF1B  intron 1. Haplotype analysis and conditional analyses provide no evidence of further independent endometrial cancer risk variants at this locus. SNP rs11263763 genotype was associated with  HNF1B  mRNA expression but not with  HNF1B  methylation in endometrial tumor samples from The Cancer Genome Atlas. Genetic analyses prioritized rs11263763 and four other SNPs in high-to-moderate linkage disequilibrium as the most likely causal SNPs. Three of these SNPs map to the extended  HNF1B  promoter based on chromatin marks extending from the minimal promoter region. Reporter assays demonstrated that this extended region reduces activity in combination with the minimal  HNF1B  promoter, and that the minor alleles of rs11263763 or rs8064454 are associated with decreased  HNF1B  promoter activity. Our findings provide evidence for a single signal associated with endometrial cancer risk at the  HNF1B  locus, and that risk is likely mediated via altered  HNF1B  gene expression.

Fine-mapping of the HNF1B multicancer locus identifies candidate variants that mediate endometrial cancer risk