title: Interleukin 6 -174G>C polymorphism and cancer risk: meta-analysis reveals a site dependent differential influence in Ancestral North Indians.
abstract: In our earlier studies, single nucleotide polymorphisms (SNPs) associated with anti-inflammatory cytokines were found to influence risk for breast cancer in western Indian women. Analysis of Interleukin 6 (IL-6) -174G>C polymorphism in this cohort (patients = 182; controls = 236) suggested a protective role for IL-6 -174C allele associated with the lower expression of the cytokine (OR = 0.54; 95% CI 0.32-0.89, dominant model). Together these observations suggested that in comparison to Caucasians, inflammation associated-cytokine gene polymorphisms may have higher influence on risk for cancer in this population. To examine this possibility we analyzed data assessing influence of Interleukin 6 (IL-6) -174G>C polymorphism on risk for various cancers. Overall, there was a marginally higher risk for rare allele homozygotes compared to wild type homozygotes (OR = 1.07; 95% CI 1.00-1.15). Increased risks for genitourinary cancers and for skin cancer were also indicated. The ethnicity based analysis indicated a protective effect of the minor allele in Ancestral North Indians (OR = 0.73; 95% CI 0.55-0.97). Site by ethnicity analysis once again revealed a significant protection against breast cancer (OR = 0.51; 95% CI = 0.37-0.70; dominant model) but an opposite influence on the risk of genitourinary malignancies (OR = 2.51; 95% CI 1.59-3.96; recessive model) in this population alone. The observations imply that contribution of IL-6 to inflammation or effector immunity may depend on the site of malignancy. Assessment of available data in relation to prognosis in breast cancer patients also revealed trends that are compatible with the observations of the meta-analysis. Thus, IL-6 -174G>C polymorphism clearly represents a potential modulator of risk for malignant disorders with ethnicity and site dependent trends. The results also support the possibility of higher influence of inflammation related cytokine gene polymorphisms on the risk for cancers in Ancestral North Indians.
authors.affiliation: Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India. Electronic address: njoshi@actrec.gov.in.
authors.forename: Narendra
authors.initials: N
authors.lastname: Joshi
authors.affiliation: Epidemiology & Clinical Trials Unit, Clinical Research Centre, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India.
authors.forename: Sadhana
authors.initials: S
authors.lastname: Kannan
authors.affiliation: Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India.
authors.forename: Nirupama
authors.initials: N
authors.lastname: Kotian
authors.affiliation: Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India.
authors.forename: Shreyas
authors.initials: S
authors.lastname: Bhat
authors.affiliation: Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India.
authors.forename: Mithila
authors.initials: M
authors.lastname: Kale
authors.affiliation: Cancer Research Institute, Advanced Centre for Treatment, Research and Education in Cancer (ACTREC), Tata Memorial Centre, Kharghar, Navi Mumbai 410210, Maharashtra, India.
authors.forename: Sujata
authors.initials: S
authors.lastname: Hake
mesh_terms: D000328:Adult; D000483:Alleles; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016022:Case-Control Studies; D005260:Female; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D007194:India; D015850:Interleukin-6 / Q000235:genetics* / Q000276:immunology; D009369:Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000276:immunology / Q000473:pathology; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D012306:Risk; D044465:White People
chemical_list: C508600:IL6 protein, human; D015850:Interleukin-6
keywords: Ancestral North Indians; Breast cancer; Case–control; IL-6 −174G>C; Meta-analysis