Dataset Information

Genome-wide association studies and colorectal cancer.

ABSTRACT: Genome-wide association studies (GWAS) provide a powerful new approach to identify common, low-penetrance susceptibility loci without prior knowledge of biologic function. Results from three GWAS conducted in populations of European ancestry are available for colorectal cancer (CRC). These studies have identified 11 disease loci that, for the majority, were not previously suspected to be related to CRC. The proportions of the familial and population risks explained by these loci are small and they currently are not useful for risk prediction. However, the power of these studies was low, indicating that a number of other loci may be identified in new ongoing GWAS, and in pooled analyses. Thus, the risk prediction ability of susceptibility markers identified in GWAS for CRC may improve as more variants are discovered. This may, in turn, have important implications for targeting high-risk individuals for colonoscopy screening.

SUBMITTER: Le Marchand L

PROVIDER: S-EPMC2756243 | biostudies-literature | 2009 Oct

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Genome-wide association studies and colorectal cancer.

Le Marchand Loïc L

Surgical oncology clinics of North America 20091001 4

Genome-wide association studies (GWAS) provide a powerful new approach to identify common, low-penetrance susceptibility loci without prior knowledge of biologic function. Results from three GWAS conducted in populations of European ancestry are available for colorectal cancer (CRC). These studies have identified 11 disease loci that, for the majority, were not previously suspected to be related to CRC. The proportions of the familial and population risks explained by these loci are small and th ...[more]

PMID: 19793573

Similar Datasets

Project description:Colorectal cancer is the second leading cause of cancer death in developed countries. Genome-wide association studies (GWAS) have successfully identified novel susceptibility loci for colorectal cancer. To follow up on these findings, and try to identify novel colorectal cancer susceptibility loci, we present results for GWAS of colorectal cancer (2,906 cases, 3,416 controls) that have not previously published main associations. Specifically, we calculated odds ratios and 95% confidence intervals using log-additive models for each study. In order to improve our power to detect novel colorectal cancer susceptibility loci, we performed a meta-analysis combining the results across studies. We selected the most statistically significant single nucleotide polymorphisms (SNPs) for replication using ten independent studies (8,161 cases and 9,101 controls). We again used a meta-analysis to summarize results for the replication studies alone, and for a combined analysis of GWAS and replication studies. We measured ten SNPs previously identified in colorectal cancer susceptibility loci and found eight to be associated with colorectal cancer (p value range 0.02 to 1.8 × 10(-8)). When we excluded studies that have previously published on these SNPs, five SNPs remained significant at p < 0.05 in the combined analysis. No novel susceptibility loci were significant in the replication study after adjustment for multiple testing, and none reached genome-wide significance from a combined analysis of GWAS and replication. We observed marginally significant evidence for a second independent SNP in the BMP2 region at chromosomal location 20p12 (rs4813802; replication p value 0.03; combined p value 7.3 × 10(-5)). In a region on 5p33.15, which includes the coding regions of the TERT-CLPTM1L genes and has been identified in GWAS to be associated with susceptibility to at least seven other cancers, we observed a marginally significant association with rs2853668 (replication p value 0.03; combined p value 1.9 × 10(-4)). Our study suggests a complex nature of the contribution of common genetic variants to risk for colorectal cancer.

Project description:BackgroundClustering of breast and colorectal cancer has been observed within some families and cannot be explained by chance or known high-risk mutations in major susceptibility genes. Potential shared genetic susceptibility between breast and colorectal cancer, not explained by high-penetrance genes, has been postulated. We hypothesized that yet undiscovered genetic variants predispose to a breast-colorectal cancer phenotype.MethodsTo identify variants associated with a breast-colorectal cancer phenotype, we analyzed genome-wide association study (GWAS) data from cases and controls that met the following criteria: cases (n = 985) were women with breast cancer who had one or more first- or second-degree relatives with colorectal cancer, men/women with colorectal cancer who had one or more first- or second-degree relatives with breast cancer, and women diagnosed with both breast and colorectal cancer. Controls (n = 1769), were unrelated, breast and colorectal cancer-free, and age- and sex- frequency-matched to cases. After imputation, 6,220,060 variants were analyzed using the discovery set and variants associated with the breast-colorectal cancer phenotype at P<5.0E-04 (n = 549, at 60 loci) were analyzed for replication (n = 293 cases and 2,103 controls).ResultsMultiple correlated SNPs in intron 1 of the ROBO1 gene were suggestively associated with the breast-colorectal cancer phenotype in the discovery and replication data (most significant; rs7430339, Pdiscovery = 1.2E-04; rs7429100, Preplication = 2.8E-03). In meta-analysis of the discovery and replication data, the most significant association remained at rs7429100 (P = 1.84E-06).ConclusionThe results of this exploratory analysis did not find clear evidence for a susceptibility locus with a pleiotropic effect on hereditary breast and colorectal cancer risk, although the suggestive association of genetic variation in the region of ROBO1, a potential tumor suppressor gene, merits further investigation.

Dataset Information

Genome-wide association studies and colorectal cancer.

Publications

Genome-wide association studies and colorectal cancer.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets