Cancer risk susceptibility loci in a Swedish population

Abstract

A germline mutation in cancer predisposing genes is known to increase the risk of more than one tumor type. In order to find loci associated with many types of cancer, a genome-wide association study (GWAS) was conducted, and 3,555 Swedish cancer cases and 15,581 controls were analyzed for 226,883 SNPs. The study used haplotype analysis instead of single SNP analysis in order to find putative founder effects. Haplotype association studies identified seven risk loci associated with cancer risk, on chromosomes 1, 7, 11, 14, 16, 17 and 21. Four of the haplotypes, on chromosomes 7, 14, 16 and 17, were confirmed in Swedish familial cancer cases. It was possible to perform exome sequencing in one patient for each of those four loci. No clear disease-causing exonic mutation was found in any of the four loci. Some of the candidate loci hold several cancer genes, suggesting that the risk associated with one locus could involve more than one gene associated with cancer risk. In summary, this study identified seven novel candidate loci associated with cancer risk. It was also suggested that cancer risk at one locus could depend on multiple contributing risk mutations/genes.

Keywords: cancer predisposition; cancer risk; cancer syndrome; genome-wide association study; haplotype association analysis.

Figure 1. Seven novel cancer risk loci/haplotypes

Chr, chromosome, H, haplotype.

Figure 2. Pedigrees

Pedigrees for the seven families, fulfilling one (of four) risk-haplotypes. For each family the case with the risk haplotype is indicated with sample-ID (★), and for all cases are shown diagnoses, Re, Rectal Cancer; Ga, Gastric Cancer; Br, Breast Cancer; Ca, Cancer; Co, Colon Cancer; Leu, Leukemia; Lym, Lymphoma; H/N, Head and Neck Cancer; Mel, Melanoma; Pr, Prostate Cancer.