Abstract
e15644 Background: We have previously suggested a syndrome with increased risk for colorectal- and other cancers, primarily gastric- and prostate cancer. The data favoured this syndrome inherited as a complex disease. Therefore, we conducted a Genome Wide Association Study (GWAS) on colorectal cancer patients, who’s relatives had prostate-, and/or gastric cancer. Methods: The GWAS analysis consisted of 685 cases of colorectal cancer and 4780 healthy controls from Sweden. A sliding window haplotype analysis was conducted using a logistic regression model.Thereafter, we performed sequencing to find candidate variants, finally to be tested in a nested case-control study. Results: Candidate loci/genes on ten chromosomal regions were suggested with odds ratios (ORs) between 1.71-3.62 and p-values < 5x10-8 in the analysis. The regions suggested were 1q32.2, 3q29, 4q35.1, 4p15.31, 4q26, 8p23.1, 13q33.3, 13q13.3, 16q23.3 and 22q11.21. All regions, except one on 1q32.2, had protein coding genes, many already shown to be involved in cancer, such as ZDHHC19, SYNPO2, PCYT1A, MYO16, TXNRD2, COMT, and CDH13. Sequencing of 122 colorectal cancer patients with gastric- and prostate cancer in their families identified 10 candidate variants from six of the loci in the haplotype regions to finally be tested in a nested case-control study of similar colorectal cancer cases and controls. Conclusions: There was some support for an increased risk of colorectal-, gastric-, and/or prostate cancer in all the six loci tested. [Table: see text]
Published Version
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