Application of identity-by-descent (IBD) approach to genetic mapping of susceptibility locus in hereditary esophageal squamous cell carcinoma (ESCC) by high density SNP array analysis

Abstract

BACKGROUND AND AIMS: Esophageal cancer (EC) is a deadly disease with a very low 5-year survival rate. The incidence of EC shows great geographical variations with high prevalence in Northern China. Although epidemiological studies suggest that environmental factors may be etiologic factors of EC, strong evidence supporting a causative role of genetic factors in familial EC comes from i) familial aggregation of EC in Yangcheng County, ii) the distinct high EC incidence in Chaoshan migrants to Nanao, and iii) molecular genetic studies such as BRCA2 germline mutations. Recent technological advances allow the identification of long regions of homozygosity (known as IBD segments) in genomic DNAs, which represent the sharing of a common ancestor in those regions, using the high density SNP arrays. Previous studies suggest that a high rate of consanguinity, which produces germline genomic homozygosity, is associated with cancers. We aim to use the IBD approach for mapping the susceptibility locus with low-penetrance SNPs in hereditary ESCC patients in Henan, one of the highest ESCC risk regions in the world. Screening programs based on knowledge of founder mutations may reduce cancer mortality by prevention. Thus, our second aim is to assess if a founder effect exists and predisposes individual…