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The effect of codon 98 of the FHIT gene on cervical cancer in Korean women
  1. S. H. Jee*,
  2. S. J. Um,
  3. J. E. Lee,
  4. S. Kim,
  5. J. H. Kim,
  6. S. J. Lee§,
  7. S. E. Namkoong§ and
  8. J. S. Park§
  1. * Department of Epidemiology and Health Promotion, Graduate School of Health Science and Management, Yonsei University, Seoul, Korea
  2. Department of Bioscience and Biotechnology, Sejong University, Seoul, Korea
  3. DNA Link, Inc.
  4. § Department of Obstetrics and Gynecology, The Catholic University of Korea, Seoul, Korea
  1. Address correspondence and reprint requests to: Jong Sup Park, MD, PhD, Department of Obstetrics and Gynecology, The Catholic University of Korea, Kangnam St. Mary's Hospital, 505 Banpo-dong, Seocho-ku, Seoul, 137–040, Korea. Email: jspark{at}cmc.cuk.ac.kr.

Abstract

The Fragile Histadine Triad (FHIT) is a putative tumor suppressor gene involved in different tumors. The objective of this study was to examine the effect of codon 98 of FHIT on cervical carcinogenesis. The study subjects were patients who were pathologically diagnosed with cervical neoplasia and who had a positive result for human papillomavirus (n = 567) compared to normal healthy women as normal controls (n = 506). The FHIT-specific sequences of DNA from peripheral blood samples from study subjects were determined by PCR using allele-specific primers and were compared with those of the controls. The genetic susceptibility of codon 98 of the FHIT gene (3p14.2) in cervical carcinogenesis was determined by examining the effect of the gene and environmental factors vs. the different stages of cervical intraepithelial lesions and the different histopathologic types of invasive cervical cancers. On assessing FHIT polymorphisms, the percentages of individuals homozygous for the T allele, homozygous for the C allele, and heterozygous for these two alleles were 42.1%, 11.3, and 46.6% in the control group. The corresponding figures were 39.5%, 14.8%, and 45.7% among in women with cervical cancer. Compared with FHIT T/ T, odds ratio (95% confidence interval) for FHIT C/C was 1.4 (0.8–2.5) for invasive cervical cancer and 1.7 (0.9–3.1) for cervical intraepithelial neoplasia (CIN) II or III. The risks for invasive cervical cancer were higher with early onset cervical carcinogenesis (2.3, 1.0–5.5, P = 0.0438), than with late onset (1.0, 0.5–2.1, P = 0.9306). The risks of FHIT C/C or C/ T also increased for ever smokers or women with two or more children compared with FHIT T/ T. Polymorphisms of FHIT are associated with a higher risk of developing cervical cancer, in particular early onset cervical carcinogenesis.

  • cervical cancer
  • FHIT
  • polymorphism

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