Single nucleotide polymorphism at Fas promoter is associated with cervical carcinogenesis.
The causal role of human papillomavirus (HPV) in cervical carcinogenesis is beyond reasonable questioning. The progression from HPV infection, squamous intraepithelial lesions (SIL) to squamous cell carcinomata (SCC), however, is very uncommon and inefficient. Host genetic factors that may confer the susceptibility of disease progression are largely unknown. Apoptosis is an important fail-safe check for tumor development, in which Fas/FasL interaction contributes substantially. The purpose of our study is to test the hypothesis that an A/G polymorphism at -670 of Fas promoter with different transcriptional activity is associated with the risk for cervical neoplasia. A hospital-based case-control study was conducted, in which 104 patients of low grade SIL (LSIL), 131 high grade SIL (HSIL) and 176 SCC as well as age-matched, 1:1 controls were tested for Fas polymorphism by PCR-RFLP. HPV genotypes were determined in case groups by MY PCR-reverse line blot. The frequency of A allele was significantly (p = 0.006) higher in SCC than in control, conferring an odd ratio of 1.5 (95% CI = 1.1-2.0). The distribution of Fas (-670) genotypes also differed significantly between HSIL, SCC and each of their control (p = 0.017 and 0.03, respectively), with the A/A genotype conferring an OR of 1.3 (95% CI = 1.1-1.6) and 1.6 (95% CI = 1.0-2.5), respectively. Remarkably, the frequency of A allele and A/A genotype increased gradually in accordance with the multi-step carcinogenesis from LSIL, HSIL to SCC (p(test for trend) = 0.0066 and 0.0007, respectively). In addition, there was no difference of Fas genotypes between HPV (+) and HPV (-) cases. Fas genotypes, however, differed in LSIL infected with different HPV types (p = 0.033). The present study demonstrated an association between Fas polymorphism and cervical carcinogenesis. We deduced a possible effect of apoptosis of immune cells in this virus-induced cancer.
Lai
Hung-Cheng
HC
Graduate Institutes of Medical Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Sytwu
Huey-Kang
HK
Sun
Chien-An
CA
Yu
Mu-Hsien
MH
Yu
Cheng-Ping
CP
Liu
Hang-Seng
HS
Chang
Cheng-Chang
CC
Chu
Tang-Yuan
TY
D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000378:metabolism; D004279:DNA, Viral / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D016017:Odds Ratio; D027383:Papillomaviridae / Q000235:genetics / Q000302:isolation & purification; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology; D002583:Uterine Cervical Neoplasms / Q000235:genetics* / Q000821:virology; D014626:Vaginal Smears; D019014:fas Receptor / Q000235:genetics*; D002578:Uterine Cervical Dysplasia / Q000235:genetics* / Q000821:virology
D017931:DNA Primers; D004273:DNA, Neoplasm; D004279:DNA, Viral; D019014:fas Receptor