Human Genetics

, Volume 132, Issue 3, pp 301–312 | Cite as

Polymorphisms of the Interleukin 6 gene contribute to cervical cancer susceptibility in Eastern Chinese women

  • Ting-Yan Shi
  • Mei-Ling Zhu
  • Jing He
  • Meng-Yun Wang
  • Qiao-Xin Li
  • Xiao-Yan Zhou
  • Meng-Hong Sun
  • Zhi-Ming Shao
  • Ke-Da Yu
  • Xi Cheng
  • Xiaohua WuEmail author
  • Qingyi WeiEmail author
Original Investigation


Interleukin 6 (IL6) encodes a cytokine protein, which functions in inflammation, maintains immune homeostasis and plays important roles in cervical carcinogenesis. Single nucleotide polymorphisms (SNPs) in IL6 that cause variations in host immune response may contribute to cervical cancer risk. In this two-stage case–control study with a total of 1,584 cervical cancer cases and 1,768 cancer-free female controls, we investigated associations between two IL6 SNPs and cervical cancer risk in Eastern Chinese women. In both Study 1 and Study 2, we found a significant association of the IL6-rs2069837 SNP with an increased risk of cervical cancer as well as in their combined data (OR 1.27 and 1.19, 95 % CI 1.08–1.49 and 1.04–1.36, P = 0.004 and 0.014 for dominant and additive genetic models, respectively). Furthermore, rs2069837 variant AG/GG carriers showed significantly higher levels of IL6 protein than did rs2069837 AA carriers in the target tissues. Using multifactor dimensionality reduction (MDR) and classification and regression tree (CART) analyses, we observed some evidence of interactions of the IL6 rs2069837 SNP with age at primiparity and menopausal status in cervical cancer risk. We concluded that the IL6-rs2069837 SNP may be a marker for susceptibility to cervical cancer in Eastern Chinese women by a possible mechanism of altering the IL6 protein expression. Although lacked information on human papillomavirus (HPV) infection, our study also suggested possible interactions between IL6 genotypes and age at primiparity or menopausal status in cervical carcinogenesis. However, larger, independent studies with detailed HPV infection data are warranted to validate our findings.


Cervical Cancer Multifactor Dimensionality Reduction Cervical Cancer Risk Multifactor Dimensionality Reduction Analysis Cervical Stromal Invasion 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.



Human papillomavirus


Interleukin 6


Single nucleotide polymorphism


Fudan University Shanghai Cancer Center


Taizhou longitudinal study


Body mass index


International Federation of Gynecology and Obstetrics


Lymph node


Lympho–vascular space invasion


Estrogen receptor


Progesterone receptor


Untranslated region


Minor allele frequency


Linkage disequilibrium


Transcription factor binding site




Multifactor dimensionality reduction


Classification and regression tree


Odds ratio


Confidence interval


False positive report probability


Hardy–Weinberg equilibrium


Cross-validation consistency


Terminal node


Chromatin immunoprecipitation



This study was supported by the funds from “China’s Thousand Talents Program” Recruitment at Fudan University and by the Shanghai Committee of Science and Technology, China (Grant No. 12DZ2260100). We would like to thank Ya-Jun Yang and Jiu-Cun Wang from Fudan University for the DNA samples of 511 controls originated from the TZL. We also thank Yu-Hu Xin and Hong-Yu Gu from Fudan University Shanghai Cancer Center for the technical and immunohistochemical support, respectively.

Conflict of interest

We declare that we have no conflict of interest.

Supplementary material

439_2012_1245_MOESM1_ESM.doc (342 kb)
Supplementary material 1 (DOC 342 kb)


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Copyright information

© Springer-Verlag Berlin Heidelberg 2012

Authors and Affiliations

  • Ting-Yan Shi
    • 1
    • 5
  • Mei-Ling Zhu
    • 1
    • 5
  • Jing He
    • 1
    • 5
  • Meng-Yun Wang
    • 1
    • 5
  • Qiao-Xin Li
    • 1
    • 5
  • Xiao-Yan Zhou
    • 1
    • 2
    • 5
  • Meng-Hong Sun
    • 2
    • 5
  • Zhi-Ming Shao
    • 3
    • 5
  • Ke-Da Yu
    • 3
    • 5
  • Xi Cheng
    • 4
    • 5
  • Xiaohua Wu
    • 4
    • 5
    Email author
  • Qingyi Wei
    • 1
    • 6
    Email author
  1. 1.Cancer InstituteFudan University Shanghai Cancer CenterShanghaiChina
  2. 2.Department of PathologyFudan University Shanghai Cancer CenterShanghaiChina
  3. 3.Department of Breast SurgeryFudan University Shanghai Cancer CenterShanghaiChina
  4. 4.Department of Gynecologic OncologyFudan University Shanghai Cancer CenterShanghaiChina
  5. 5.Department of OncologyShanghai Medical College, Fudan UniversityShanghaiChina
  6. 6.Department of EpidemiologyThe University of Texas M.D. Anderson Cancer CenterHoustonUSA

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