TNF-Alpha rs1800629 Polymorphism Is Not Associated with HPV Infection or Cervical Cancer in the Chinese Population
et al. (2012) TNF-Alpha rs1800629 Polymorphism Is Not Associated with HPV Infection or Cervical Cancer in the
Chinese Population. PLoS ONE 7(9): e45246. doi:10.1371/journal.pone.0045246
TNF-Alpha rs1800629 Polymorphism Is Not Associated with HPV Infection or Cervical Cancer in the Chinese Population
Ning Wang 0
Duo Yin 0
Shulan Zhang 0
Heng Wei 0
Shizhuo Wang 0
Yang Zhang 0
Yanming Lu 0
Shuyan Dai 0
Wei Li 0
Qiao Zhang 0
Yao Zhang 0
Cordula M. Stover, University of Leicester, United Kingdom
0 1 Department of Gynecology and Obstetrics, Shengjing Hospital of China Medical University , Shenyang , China , 2 Department of Breast Surgery, Shengjing Hospital of China Medical University , Shenyang , China
Background: While HPV infection is the main cause of cervical cancer, genetic susceptibility to HPV infection is not well understood. Tumor necrosis factor alpha (TNF-alpha), involved in the defense against HPV infection, plays an important role in cervical cancer progression and regression. The aim of this study was to investigate the relationship between the TNFalpha rs1800629 polymorphism and risk of HPV infection or cervical cancer. Methods: Three groups were involved in this study of Chinese women. Group 1 consisted of 285 high risk HPV positive cervical cancer patients, Group 2, 225 high risk HPV positive patients without cervical cancer, and Group 3, 318 HPV negative women with no cervical cancer. Blood samples were obtained from all patients and genotyped by PCR-RLFP. Fifty randomly selected samples were further sequenced. Results: The allele and genotype distributions of the TNF-alpha rs1800629 polymorphism were not significantly different between each of the groups (P.0.05). There are no significant relationship between rs1800629 polymorphism and high risk HPV infection (OR = 0.649, 95% CI: 0.253-1.670, P = 0.371), cervical cancer (OR = 0.993, 95% CI: 0.376-2.618, P = 0.988), or cervical cancer with HPV infection (OR = 0.663, 95% CI: 0.250-1.758, P = 0.409). Conclusions: We demonstrated that there is no association between TNF rs1800629 polymorphism and the HPV infection, or cervical cancer with HPV infection.
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Funding: This study was supported by the National Nature Science Foundation of China (No. 30973191), Science and Technology Program of Liaoning Province
(No.2008225004), Peak Medical Construction Special Project of Liaoning Province (No.2010696), Science and Technology Program of Shenyang City
(No.F11-2629-15) and Free Researcher Project of Shengjing Hospital (No.200806). The funders had no role in study design, data collection and analysis, decision to publish, or
preparation of the manuscript.
Competing Interests: The authors have declared that no competing interests exist.
Cervical cancer remains the second most common cancer
among women worldwide [1]. Infection by an oncogenic human
papillomavirus (HPV) is a risk factor for developing cervical cancer
[2]. Immune responses to HPV infection within the cervical
epithelium play an important role in the pathogenesis of cervical
cancer.
Several cytokines that modulate the immunologic response have
been implicated in the development of cancer [3]. Tumor necrosis
factor-alpha (TNF-a), secreted mainly by activated macrophages,
is an extraordinarily pleiotropic cytokine with a central role in
immune homeostasis, inflammation, and host defense [4,5].
TNFa is involved in the defense against HPV infection, modulating
viral replication [6].
The role of TNF-a in cancer is not well understood.
Deregulated TNF expression within the tumor microenvironment
appears to favor malignant cell tissue invasion, migration, and
ultimately metastasis formation [7]. There is also evidence,
however, that TNF-a may promote the development and spread
of the cancer [8,9]. The role of TNF-a in tumor promotion is
supported by the TNF-a-deficient mouse model, in which
TNFa2/2 mice are resistant to the development of benign and
malignant skin tumors. TNF modulation may contribute to
regulation of cell inflammation, and the subsequent development
of malignant disease [10]. Since the malignant development of
cervical cancer is induced by persistent viral infection, we focus on
the TNF gene, which may be involved in the susceptibility to HPV
infection and development of cervical cancer.
TNF-a is regulated at the transcriptional level [11] and the
rs1800629 polymorphisms within the TNF-a promoter region
have been associated with the level of TNF-a [12]. The association
of rs1800629 polymorphism and cervical cancer has been widely
studied, but the results are contradictory [13,14,15,16]. The
current study was conducted to investigate the distribution of
Group 1 (n = 285)
Group 2 (n = 225)
Group 3 (n = 318)
Clinical stage*
Note: * According to the International Federation of Gynecology and Obstetrics classification.
doi:10.1371/journal.pone.0045246.t001
rs1800629 polymorphism and its relationship with HPV infection
and cervical cancer.
Materials and Methods
Study subject (...truncated)