A population-based case-control study of genetic variation in cytokine genes associated with risk of cervical and vulvar cancers

作者：Hardikar Sheetal; Johnson Lisa G; Malkki Mari; Petersdorf Effie W; Galloway Denise A; Schwartz Stephen M; Madeleine Margaret M^*

来源：Gynecologic Oncology, 2015, 139(1): 90-96.

DOI：10.1016/j.ygyno.2015.07.110

• Cervical cancer
• Vulvar cancer
• T-helper 1 pathways
• T-helper 2 pathway
• T-helper 17 pathway
• Genetic variation

Objective. Persistent infection with oncogenic human papillomavirus (HPV) is known to be the necessary cause of cervical cancer and a majority of vulvar cancers. Persistent HPV infections must evade host immune responses, including cytokines released by activated 1-helper (Th) cells. In this study, we investigated the risk of cervical and vulvar cancers associated with common genetic variations in 560 tagging single-nucleotide polymorphisms (SNPs) in candidate cytokine genes.
Methods. The study included 399 invasive squamous cell carcinomas (SCCs) and 502 in situ or invasive adenocarcinomas (AC) of the cervix; 357 in situ or invasive vulvar SCC; and 1109 controls from the Seattle-area case-control studies of HPV-related cancers. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) using a log additive model, with adjustment for multiple testing.
Results. Statistically significant risks were observed for HPV16-containing SCC of the cervix with the variant allele rs879576 in IL17RA and rs2229094 in TNF [OR, 95% Cl and multiple-testing corrected p: 1.91 (1.30-2.79), p = 0.018 and 0.61 (0.45-0.83), p = 0.02, respectively]. We also observed significantly increased risk of HPV-positive vulvar cancers associated with variant alleles in CSF2 (rs25882 and rs27438, 26-28% increased risk) and IL-12B (rs2569254 and rs3181225, 40-41% increased risk) genes.
Conclusions. We found that variation in several Th-cytokine genes is significantly associated with cervical and vulvar cancer risk. The strong association between these HPV-related cancers and common variation in cytokine genes in the Th1 and Th17 pathways may be important for development of new therapies.

• 出版日期2015-10