Carcinogenesis

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Genetic polymorphism of the interferon-γ gene in cervical carcinogenesis

  1. Hung-Cheng Lai1,
  2. Cheng-Chang Chang1,
  3. Ya-Wen Lin2,
  4. Su-Feng Chen3,
  5. Mu-Hsien Yu1,
  6. Shin Nieh4,
  7. Ta-Wei Chu5,
  8. Tang-Yuan Chu1,2,†,*

Article first published online: 21 OCT 2004

DOI: 10.1002/ijc.20637

Issue

International Journal of Cancer

International Journal of Cancer

Volume 113, Issue 5, pages 712–718, 20 February 2005

Additional Information

How to Cite

Lai, H.-C., Chang, C.-C., Lin, Y.-W., Chen, S.-F., Yu, M.-H., Nieh, S., Chu, T.-W. and Chu, T.-Y. (2005), Genetic polymorphism of the interferon-γ gene in cervical carcinogenesis. Int. J. Cancer, 113: 712–718. doi: 10.1002/ijc.20637

Author Information

  1. 1

    Department of Obstetrics and Gynecology, Tri-Service General Hospital, Taipei, Taiwan

  2. 2

    Graduate Institutes of Medical Sciences, National Defense Medical Center, Taipei, Taiwan

  3. 3

    Institute of Clinical Dental Science, School of Dentistry, National Yang-Ming University, Taipei, Taiwan

  4. 4

    Department of Pathology, Tri-Service General Hospital, Taipei, Taiwan

  5. 5

    Department of Obstetrics and Gynecology, Army Forces Taoyuan General Hospital, Taoyuan, Taiwan

  1. †

    Fax: +886-2-8792-7199

*Department of Obstetrics and Gynecology, Tri-Service General Hospital, 325, Section 2, Cheng-Gung Road, Taipei 114, Taiwan

Publication History

  1. Issue published online: 8 DEC 2004
  2. Article first published online: 21 OCT 2004
  3. Manuscript Accepted: 6 AUG 2004
  4. Manuscript Received: 16 MAR 2004

Funded by

  • Tri-Service General Hospital, Taiwan. Grant Numbers: DOD-92-115, TSGH-C93-05-S02
  • National Science Council, Taiwan. Grant Numbers: NSC92-3112-B016-005, NSC92-3112-B016-006, NSC92-2314-B016-077
  • Taoyuan General Hospital, Taiwan. Grant Number: 804-9302
  • C.Y. Chai Foundation for Advancement of Education, Sciences and Medicine

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Keywords:

  • cervical cancer;
  • human papillomavirus;
  • IFN-γ;
  • polymorphism

Abstract

Beyond human papillomavirus (HPV) infection, host genetic factors may contribute to cervical carcinogenesis. This study aims to test the hypothesis that CA-dinucleotide repeat polymorphism in the first intron of the interferon-gamma (IFN-γ) gene is associated with HPV-initiated cervical carcinogenesis. A hospital-based case-control study including patients with low-grade squamous intraepithelial lesions (LSILs; n = 93), high-grade squamous intraepithelial lesions (HSILs; n = 123) and invasive carcinomas (n = 153) of the uterine cervix, as well as 1:1 age-matched controls, was conducted. The IFN-γ genotype was determined by PCR and capillary electrophoresis with internal standards. HPV genotype was determined by consensus PCR and reverse line blot hybridization. Genotypes containing the 12 or 14 allele (12 or 14 CA repeats) were significantly more common in patients with HSILs than in controls (46% vs. 22%; OR = 3.0; 95% CI = 1.7–5.2; p < 0.0001). In contrast, genotypes containing 13 and 18 were significantly more common in controls than in patients with HSILs (76% vs. 53%; OR = 0.3; 95% CI = 0.2–0.6; p = 0.0001) or squamous cell carcinomas (74% vs. 63%; OR = 0.6; 95% CI = 0.4–1.0; p = 0.037). The frequency of the 12 and 14 genotypes increased significantly in accordance with the severity of cervical carcinogenesis (ptest for trend = 0.0002), whereas the 13 and 18 genotypes showed the opposite trend (ptest for trend = 0.007). Comparing IFN-γ genotype and HPV status, 18-containing genotypes were more frequently found in HPV+ LSILs, and 12-containing genotypes were less frequently found in HPV+ HSILs. Compared with non-13 genotypes, 13 genotype HSILs were more frequently infected with HPV58 (70% vs. 45%) and less frequently infected with HPV18 (0% vs. 16%; p= 0.007). Genetic polymorphism of the IFN-γ gene is associated with individual susceptibility to cervical carcinogenesis. This polymorphism correlates with HPV infection in a disease- and type-specific manner. © 2004 Wiley-Liss, Inc.

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