Article

DCC (Deleted in Colorectal Carcinoma) Gene Variants Confer Increased Susceptibility to Gallbladder Cancer (Ref. No.: GENE-D-12-01446).

Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, India.
Gene (Impact Factor: 2.2). 01/2013; 518(2). DOI: 10.1016/j.gene.2013.01.019
Source: PubMed

ABSTRACT BACKGROUND AND AIM: GBC is a lethal and multifaceted disease. Deleted in colorectal carcinoma (DCC) is well known tumour suppressor gene. Recently a small genome-wide association study (GWAS) identified DCC to be significantly associated with gallbladder cancer (GBC) susceptibility in Japanese population. However, the study sample size was small and lacked independent replication. Therefore, the present study was carried out to replicate the association of two GWAS identified DCC SNPs (A>G(rs4078288,) C>T(rs7504990)) and two other SNPs (C>G(rs2229080) and A>G(rs714)) previously associated with various cancers. METHODOLOGY: The study was accomplished in 406 GBC cases and 260 healthy control samples from North India. Genotyping was carried out by PCR-RFLP and Taqman genotyping assays. Statistical analysis was performed by using SPSS ver16 and functional prediction of these variants were carried out using Bioinformatics tools (FAST-SNP, F-SNP). RESULT: We did not observe association with GWAS-identified SNPs of DCC but other SNPs showed significant association. In addition, a DCC haplotype G (rs2229080)-A (rs4078288)-C (rs7504990)-A (rs714) conferred high risk of GBC in India. The haplotype associated risk was independent of gallstone, sex or tobacco usages which are well-known modifiers of GBC risk. Further analysis suggested DCC A>G(rs714) as major risk conferring SNP in Indian population. CONCLUSION: This study re-affirms the role of the plausible tumour suppressor DCC variants, in gallbladder carcinogenesis and the risk haplotype may be explored as useful marker for GBC susceptibility.

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