Jee S H, Um S J, Lee J E, Kim S, Kim J H, Lee S J, Namkoong S E, Park J S
Department of Epidemiology and Health Promotion, Graduate School of Health Science and Management, Yonsei University, Seoul, Korea.
Int J Gynecol Cancer. 2003 Nov-Dec;13(6):843-8. doi: 10.1111/j.1525-1438.2003.13616.x.
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.
脆性组氨酸三联体（FHIT）是一种推定的肿瘤抑制基因，与多种肿瘤相关。本研究的目的是检测FHIT基因第98密码子对宫颈癌发生的影响。研究对象为经病理诊断为宫颈肿瘤且人乳头瘤病毒检测呈阳性的患者（n = 567），以正常健康女性作为正常对照（n = 506）。使用等位基因特异性引物通过聚合酶链反应（PCR）测定研究对象外周血样本中FHIT特异性DNA序列，并与对照组进行比较。通过检测该基因和环境因素对宫颈上皮内病变不同阶段以及浸润性宫颈癌不同组织病理学类型的影响，确定FHIT基因（3p14.2）第98密码子在宫颈癌发生中的遗传易感性。在评估FHIT基因多态性时，对照组中T等位基因纯合子、C等位基因纯合子以及这两个等位基因杂合子个体的百分比分别为42.1%、11.3%和46.6%。宫颈癌女性中的相应数字分别为39.5%、14.8%和45.7%。与FHIT T/T相比，浸润性宫颈癌中FHIT C/C的优势比（95%置信区间）为1.4（0.8 - 2.5），宫颈上皮内瘤变（CIN）II或III中为1.7（0.9 - 3.）。早期发生的宫颈癌浸润风险更高（2.3，1.0 - 5.5，P = 0.0438），而晚期发生的风险较低（1.0，0.5 - 2.1，P = 0.9306）。与FHIT T/T相比，曾经吸烟或育有两个或更多子女的女性中，FHIT C/C或C/T的风险也有所增加。FHIT基因多态性与患宫颈癌的风险较高相关，尤其是早期发生的宫颈癌。
