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 Wu
  • Qingyi Wei
Original Investigation

Abstract

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.

Abbreviations

HPV

Human papillomavirus

IL6

Interleukin 6

SNP

Single nucleotide polymorphism

FUSCC

Fudan University Shanghai Cancer Center

TZL

Taizhou longitudinal study

BMI

Body mass index

FIGO

International Federation of Gynecology and Obstetrics

LN

Lymph node

LVSI

Lympho–vascular space invasion

ER

Estrogen receptor

PR

Progesterone receptor

UTR

Untranslated region

MAF

Minor allele frequency

LD

Linkage disequilibrium

TFBS

Transcription factor binding site

IHC

Immunohistochemistry

MDR

Multifactor dimensionality reduction

CART

Classification and regression tree

OR

Odds ratio

CI

Confidence interval

FPRP

False positive report probability

HWE

Hardy–Weinberg equilibrium

CVC

Cross-validation consistency

TN

Terminal node

ChIP

Chromatin immunoprecipitation

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
  • Qingyi Wei
    • 1
    • 6
  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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