DCC (deleted in colorectal carcinoma) gene variants confer increased susceptibility to gallbladder cancer (Ref. No.: Gene-D-12-01446).
OBJECTIVE
GBC is a lethal and multifaceted disease. Deleted in colorectal carcinoma (DCC) is a well known tumor suppressor gene. Recently a small genome-wide association study (GWAS) identified DCC to be significantly associated with gallbladder cancer (GBC) susceptibility in a Japanese population sample. 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>Grs4078288, C>Trs7504990) and two other SNPs (C>Grs2229080 and A>Grs714) previously associated with various cancers.


METHODS
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 was carried out using Bioinformatics tools (FAST-SNP, F-SNP).


RESULTS
We did not observe association with GWAS-identified SNPs of DCC but other SNPs showed significant association. In addition, a DCC haplotype Grs2229080-Ars4078288-Crs7504990-Ars714 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>Grs714 as a major risk conferring SNP in the Indian population.


CONCLUSIONS
This study re-affirms the role of plausible tumor suppressor DCC variants, in gallbladder carcinogenesis and the risk haplotype may be explored as a useful marker for GBC susceptibility.
Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, India.
Rajani
R
Rai
Kiran L
KL
Sharma
Swati
S
Tiwari
Sanjeev
S
Misra
Ashok
A
Kumar
Balraj
B
Mittal
D000075389:DCC Receptor; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics*; D042882:Gallstones / Q000150:complications; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011956:Receptors, Cell Surface / Q000235:genetics*; D012306:Risk; D025521:Tumor Suppressor Proteins / Q000235:genetics*
D000075389:DCC Receptor; C501909:DCC protein, human; D011956:Receptors, Cell Surface; D025521:Tumor Suppressor Proteins