Association analyses identify 31 new risk loci for colorectal cancer susceptibility

Abstract

Colorectal cancer (CRC) is a leading cause of cancer-related death worldwide, and has a strong heritable basis. We report a genome-wide association analysis of 34,627 CRC cases and 71,379 controls of European ancestry that identifies SNPs at 31 new CRC risk loci. We also identify eight independent risk SNPs at the new and previously reported European CRC loci, and a further nine CRC SNPs at loci previously only identified in Asian populations. We use in situ promoter capture Hi-C (CHi-C), gene expression, and in silico annotation methods to identify likely target genes of CRC SNPs. Whilst these new SNP associations implicate target genes that are enriched for known CRC pathways such as Wnt and BMP, they also highlight novel pathways with no prior links to colorectal tumourigenesis. These findings provide further insight into CRC susceptibility and enhance the prospects of applying genetic risk scores to personalised screening and prevention.

Effects of common genetic variants associated with colorectal cancer risk on survival outcomes after diagnosis: A large population‐based cohort study

“…None of the nominally significant genetic variants have known detrimental clinically relevant effects on gene function (Supporting Information Table S6). Rs3087967, which is located 3'UTP of C11orf53, is known to be associated with higher COLCA2 and C11orf53 expression in colon transverse tissue for C allele . However, little is known about COLCA2 and C11orf53 functions.…”

“…Genotyping was conducted using the Illumina HumanHap300, HumanHap240S and OmniExpressExome BeadChip 8v1 arrays. Standard quality control measures were applied as described previously . Untyped variants were imputed using SHAPEIT v2 and IMPUTEv2 softwares based on a merged reference panel comprising of 1,000 Genomes Project (phase 1, December 2013 release) and UK10K (April 2014 release) samples.…”

“…Untyped variants were imputed using SHAPEIT v2 and IMPUTEv2 softwares based on a merged reference panel comprising of 1,000 Genomes Project (phase 1, December 2013 release) and UK10K (April 2014 release) samples. We excluded poorly imputed variants (information measure <0.80) and rare variants (minor allele frequency [MAF] <0.05%) as presented in the previous publication . Death registration and cause of death was ascertained from the Scottish Cancer Registry (SCR), and patients were prospectively followed up until death or July 1, 2017 (censored date), whichever came first.…”

Characterization of lncRNA LINC00520 and functional polymorphisms associated with breast cancer susceptibility in Chinese Han population

“…With the development of high‐throughput technology, emerging evidence demonstrated that genetic alterations, including single‐nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations, were associated with the risk of various diseases including BC . Notably, SNPs, especially in irregular regions of protein‐coding and related with diseases, have been extensively studied and reported widely .…”

“…With the development of high-throughput technology, emerging evidence demonstrated that genetic alterations, including single-nucleotide polymorphisms (SNPs), insertions, deletions, and copy number variations, were associated with the risk of various diseases including BC. 5,6 Notably, SNPs, especially in irregular regions of protein-coding and related with diseases, have been extensively studied and reported widely. 7 The expression of the same lncRNA transcripts varies by different health conditions, age, tissues, even cells, which can indicate their potential as possible biomarkers and be predictive of diagnosis and prognosis of diseases.…”