title: Association of genetic variants of cancer stem cell gene CD44 haplotypes with gallbladder cancer susceptibility in North Indian population.
abstract: CD44 is an important marker for cancer stem cells. Germline variants in CD44 gene have been associated with susceptibility to breast and nasopharyngeal carcinomas but no study in gallbladder cancer (GBC) has been done yet. The present study included 405 GBC patients and 200 healthy controls from North India. Tagger SNPs for CD44 were selected from the GIH population data. Genotyping was carried out by PCR-RFLP and Taqman probes. Statistical analysis was done by SPSS. Bonferroni correction was applied in subgroup analysis. Logistic regression analysis showed no individual association of CD44 polymorphisms with GBC risk. However, [CCAT] haplotype was associated with overall reduced risk of GBC [P = 0.04, odds ratios (OR) = 0.47]. Gender stratification revealed that [CCAT] and [TAGT] haplotypes were significantly associated with decreased risk in female GBC patients [P = 0.022, OR = 0.38; P = 0.011, OR = 0.17, respectively]. The CAAT haplotype was marginally associated with low GBC risk in patients with co-existing gallstones [P = 0.026, OR = 0.53]. The cancer risk was not further modified with tobacco usage or age of onset. In silico analysis showed change in transcriptional regulation of selected SNPs. This study reports an important role of CD44 haplotypes with reduced risk of GBC.
authors.affiliation: Department of Genetics, Sanjay Gandhi Post Graduate Institute of Medical Sciences (SGPGIMS), Lucknow, 226014, Uttar Pradesh, India, kiran_sharmadav@yahoo.co.in.
authors.forename: Kiran Lata
authors.initials: KL
authors.lastname: Sharma
authors.forename: Anu
authors.initials: A
authors.lastname: Yadav
authors.forename: Annapurna
authors.initials: A
authors.lastname: Gupta
authors.forename: Sonam
authors.initials: S
authors.lastname: Tulsayan
authors.forename: Vijay
authors.initials: V
authors.lastname: Kumar
authors.forename: Sanjeev
authors.initials: S
authors.lastname: Misra
authors.forename: Ashok
authors.initials: A
authors.lastname: Kumar
authors.forename: Balraj
authors.initials: B
authors.lastname: Mittal
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D044466:Asian People / Q000235:genetics; D005260:Female; D005706:Gallbladder Neoplasms / Q000235:genetics*; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D018960:Hyaluronan Receptors / Q000235:genetics*; D007194:India; D008297:Male; D008875:Middle Aged; D014411:Neoplastic Stem Cells / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: C497483:CD44 protein, human; D018960:Hyaluronan Receptors