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Cervical and Vulvar Cancer Risk in Relation to the Joint Effects of Cigarette Smoking and Genetic Variation in Interleukin 2.

Hussain, Shehnaz K. and Madeleine, Margaret M. and Johnson, Lisa G. and Du, Qin Du and Malkki, Mari and Wilkerson, Hui-Wen and Farin, Federico M. and Carter, Joseph J. and Galloway, Denise A. and Daling, Janet R. and Petersdorf, Effie W. and Schwartz, Stephen M. (2008) Cervical and Vulvar Cancer Risk in Relation to the Joint Effects of Cigarette Smoking and Genetic Variation in Interleukin 2. Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology, 17 (7). pp. 1790-1799. ISSN 1055-9965

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Cigarette smoking is an established cofactor to human papillomavirus (HPV) in the development of cervical and vulvar squamous cell carcinoma (SCC), and may influence risk through an immunosuppressive pathway. Genetic variation in interleukin 2 (IL2), associated in some studies with the inhibition of HPV-targeted immunity, may modify the effect of smoking on the risk of HPV-related anogenital cancers. We conducted a population-based case-only study to measure the departure from a multiplicative joint effect of cigarette smoking and IL2 variation on cervical and vulvar SCC. Genotyping of the four IL2 tagSNPs (rs2069762, rs2069763, rs2069777, and rs2069778) was done in 399 cervical and 486 vulvar SCC cases who had been interviewed regarding their smoking history. Compared with cases carrying the rs2069762 TT genotype, we observed significant departures from multiplicativity for smoking and carriership of the TG or GG genotypes in vulvar SCC risk [interaction odds ratio (IOR), 1.67; 95% confidence interval (CI), 1.16-2.41]. Carriership of one of three diplotypes, together with cigarette smoking, was associated with either a supramultiplicative (TGCT/GGCC; IOR, 2.09; 95% CI, 0.98-4.46) or submultiplicative (TTCC/TGTC; IOR, 0.37; 95% CI, 0.16-0.85 or TGCT/TGCC; IOR, 0.37; 95% CI, 0.15-0.87) joint effect in vulvar cancer risk. For cervical SCC, departure from multiplicativity was observed for smokers homozygous for the rs2069763 variant allele (TT versus GG or GT genotypes; IOR, 1.87; 95% CI, 1.00-3.48), and for carriership of the TTCC/TTCC diplotype (IOR, 2.08; 95% CI, 1.01-4.30). These results suggest that cervical and vulvar SCC risk among cigarette smokers is modified by genetic variation in IL2. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1790-9).

Item Type: Article
Additional Information: The final version of this article is freely available at the journal website.
DOI: 10.1158/1055-9965.EPI-07-2753
PubMed ID: 18628433
PMCID: PMC2497438
Grant Numbers: R01 CA112512-01, R25 CA094880-06, P30 ES007033-14, P01 CA042792-110004
Keywords or MeSH Headings: MH - Adolescent MH - Adult MH - Aged MH - Alleles MH - DNA, Neoplasm/*genetics MH - Female MH - Genetic Predisposition to Disease MH - *Genetic Variation MH - Genotype MH - Humans MH - Incidence MH - Interleukin-2/blood/*genetics MH - Middle Aged MH - Polymerase Chain Reaction MH - Prognosis MH - Retrospective Studies MH - Smoking/*adverse effects/blood/epidemiology MH - Tumor Markers, Biological/blood/genetics MH - Uterine Cervical Neoplasms/blood/*epidemiology/etiology MH - Vulvar Neoplasms/blood/*epidemiology/etiology MH - Washington/epidemiology MH - Young Adult
Subjects: Diseases > Solid tumors > Cervical cancer
Psychology > Behavior > Smoking
Cellular and Organismal Processes > Immune Response
Research Methodologies > Epidemiology > Risk assessment
Depositing User: Library Staff
Date Deposited: 25 Sep 2008 21:43
Last Modified: 14 Feb 2012 14:42

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