title: Interleukin-12 and interleukin-6 gene polymorphisms and risk of bladder cancer in the Iranian population.
abstract: Interleukin-12 (IL-12) as an antitumor and interleukin-6 (IL-6) as an inflammatory cytokine, are immunomodulatory products that play important roles in responses in cancers and inflammation. We tested the association between two polymorphisms of IL-12(1188A>C; rs3212227) and IL-6 (-174 C>G) and the risk of bladder cancer in 261 patients and 251 healthy individuals. We also investigated the possible association of these SNPs in patients with high-risk jobs and smoking habits with the incidence of bladder cancer. The genotype distributions of IL-6 (-174 C/G) genotype were similar between the cases and the control groups; however, among patients with smoking habits, the association between IL-6 gene polymorphism and incidence of bladder cancer was significant. After a control adjustment for age and sex, the following results were recorded: CC genotype (OR= 2.11, 95%CI=1.56-2.87, p=0.007), GC genotype (OR=2.18, 95%CI=1.16-4.12, p=0.014) and GC+ CC (OR=2.6, 95%CI=1.43-4.47, p=0.011). A significant risk of bladder cancer was observed for the heterozygous genotype (AC) of IL-12 (OR=1.47, 95%CI=1.01-2.14, p=0.045) in all cases, and among smokers (AC) (OR=3.13, 95%CI=1.82-5.37, p=0.00014), combined AC+CC (OR=3.05, 95%CI=1.8-5.18, p=0.000015). Moreover among high risk job patients, there was more than a 3-fold increased risk of cancer in the carriers of IL-12 beta heterozygous (OR=3.7, 95%CI=2.04-6.57, p=0.000056) and combined AC+CC(OR=3.29, 95%CI=1.58-5.86, p=0.00002) genotypes as compared with the AA genotype with low-risk jobs. As a conclusion, this study suggests that IL-12(3'UTR A>C) and IL-6 (-174 C>G) genotypes are significantly associated with an increased risk of bladder cancer in the Iranian population with smoking habits and/or performing high-risk jobs.
authors.affiliation: Department of Medical Genetics, School of Medicine Tehran University of Medical Sciences, Tehran, Iran E-mail : s.hosseini1@med.miami.edu.
authors.forename: Nader
authors.initials: N
authors.lastname: Ebadi
authors.forename: Marzieh
authors.initials: M
authors.lastname: Jahed
authors.forename: Mohamad
authors.initials: M
authors.lastname: Mivehchi
authors.forename: Tayebeh
authors.initials: T
authors.lastname: Majidizadeh
authors.forename: Mojgan
authors.initials: M
authors.lastname: Asgary
authors.forename: Seyed Ali
authors.initials: SA
authors.lastname: Hosseini
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D005260:Female; D005500:Follow-Up Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000235:genetics*; D015850:Interleukin-6 / Q000235:genetics*; D007492:Iran / Q000453:epidemiology; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D011110:Polymorphism, Genetic / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D001749:Urinary Bladder Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology
chemical_list: C500879:IL12B protein, human; C508600:IL6 protein, human; D053762:Interleukin-12 Subunit p40; D015850:Interleukin-6