Lack of an association between a functional polymorphism in the interleukin-6 gene promoter and breast cancer risk: a meta-analysis involving 25,703 subjects
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The association between a single-nucleotide polymorphism (SNP) −174G > C (rs1800795) located in the IL-6 gene promoter and breast cancer risk is still controversial and ambiguous. We performed in this study a more precise estimation of the relationship by meta-analyzing the currently available evidence from literature. A total of 11 publications containing 12 studies including 10,137 cases and 15,566 controls were identified. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess the strength of association in the codominant model, dominant model, and recessive model. When all the studies were pooled into the meta-analysis, there was no evidence showing a significant association between −174G > C and breast cancer risk (for CC vs. GG: OR = 1.024, 95% CI: 0.935–1.121; for GC vs. GG: OR = 1.008, 95% CI: 0.946-1.073; for dominant model: OR = 0.980, 95% CI: 0.857–1.121; and for recessive model: OR = 1.027, 95% CI: 0.944–1.117). In the subgroup analyses by ethnicity, no significant associations were observed in any genetic models. In summary, the present meta-analysis suggests that the functional polymorphism −174G > C within the IL-6 gene promoter is not associated with breast cancer risk. Identifying a unique SNP as a breast cancer risk predictor remains a very challenging task.
KeywordsInterleukin-6 rs1800795 Breast cancer Susceptibility Meta-analysis
This research is supported by grants from the National Basic Research Program of China (2006CB910501) and the National Natural Science Foundation of China (30971143, 30972936).
- 8.Heikkila K, Harris R, Lowe G, Rumley A, Yarnell J, Gallacher J, Ben-Shlomo Y, Ebrahim S, Lawlor DA (2009) Associations of circulating C-reactive protein and interleukin-6 with cancer risk: findings from two prospective cohorts and a meta-analysis. Cancer Causes Control 20:15–26CrossRefPubMedGoogle Scholar
- 10.Fishman D, Faulds G, Jeffery R, Mohamed-Ali V, Yudkin JS, Humphries S, Woo P (1998) The effect of novel polymorphisms in the interleukin-6 (IL-6) gene on IL-6 transcription and plasma IL-6 levels, and an association with systemic-onset juvenile chronic arthritis. J Clin Invest 102:1369–1376CrossRefPubMedPubMedCentralGoogle Scholar
- 13.Snoussi K, Strosberg AD, Bouaouina N, Ben Ahmed S, Chouchane L (2005) Genetic variation in pro-inflammatory cytokines (interleukin-1beta, interleukin-1alpha and interleukin-6) associated with the aggressive forms, survival, and relapse prediction of breast carcinoma. Eur Cytokine Netw 16:253–260PubMedGoogle Scholar
- 16.Vogel U, Christensen J, Nexo BA, Wallin H, Friis S, Tjonneland A (2007) Peroxisome proliferator-activated receptor-gamma2 Pro12Ala, interaction with alcohol intake and NSAID use, in relation to risk of breast cancer in a prospective study of Danes. Carcinogenesis 28:427–434CrossRefPubMedGoogle Scholar
- 19.Slattery ML, Curtin K, Baumgartner R, Sweeney C, Byers T, Giuliano AR, Baumgartner KB, Wolff RR (2007) IL6, aspirin, nonsteroidal anti-inflammatory drugs, and breast cancer risk in women living in the southwestern United States. Cancer Epidemiol Biomarkers Prev 16:747–755CrossRefPubMedGoogle Scholar
- 23.Dossus L, Kaaks R, Canzian F, Albanes D, Berndt SI, Boeing H, Buring J, Chanock SJ, Clavel-Chapelon F, Feigelson HS, Gaziano JM, Giovannucci E, Gonzalez C, Haiman CA, Hallmans G, Hankinson SE, Hayes RB, Henderson BE, Hoover RN, Hunter DJ, Khaw KT, Kolonel LN, Kraft P, Ma J, Le Marchand L, Lund E, Peeters PH, Stampfer M, Stram DO, Thomas G, Thun MJ, Tjonneland A, Trichopoulos D, Tumino R, Riboli E, Virtamo J, Weinstein SJ, Yeager M, Ziegler RG and Cox DG (2009) PTGS2 and IL6 Genetic Variation and Risk of Breast and Prostate Cancer: results from the Breast and Prostate Cancer Cohort Consortium (BPC3). Carcinogenesis (in press)Google Scholar