Genetic polymorphisms of FAS and FASL (CD95/CD95L) genes in cervical carcinogenesis

An analysis of haplotype and gene-gene interaction

Hung Cheng Lai, Wei Yu Lin, Ya Wen Lin, Cheng Chang Chang, Mu Hsien Yu, Chia Chi Chen, Tang Yuan Chu

Research output: Contribution to journalArticle

62 Citations (Scopus)

Abstract

Objective. Whereas human papillomavirus (HPV) infection is necessary but not sufficient for cervical carcinogenesis, host genetic variations may confer individual susceptibility. Resistance to apoptosis is a hallmark of cancer in which FAS/FAS ligand signaling plays an important role. The present study examines the hypothesis that genetic polymorphisms in FAS and FAS ligand genes, alone or in combination, are associated with cervical carcinogenesis. Methods. The genotypes of FAS -670A/G, FAS -1377G/A, and FASL -844C/T were assessed in 143 patients with high-grade squamous intraepithelial lesions (HSIL), 175 patients with invasive squamous cell carcinomas (SCC), and in age-matched controls by real-time PCR with allele-specific TaqMan probes. The status of cervical high-risk HPV infection was determined and adjusted to test the independence of genotype in the risk assessment. Results. The A-allele and AA-genotype frequencies of FASA -670G were significantly higher in HSIL/SCC than in controls (60% vs. 54%, P = 0.04, OR 1.26 [95% CI 1.01-1.57]; 38.0% vs. 28.6%, P = 0.02, OR 1.70 [95% CI 1.07-2.70]). No association between FAS -1377 or FASL -844 polymorphisms and HSIL/SCC could be identified. The FAS -1377A/-670A haplotype conferred a higher risk for HSIL/SCC (OR 3.05, 95% CI 1.28-7.30) than FAS -670A alone (OR 1.26, 95% CI 1.28-7.30). The interaction between FAS -670AA and FASL -844CC genotypes was associated with a risk of HSIL/SCC (OR 2.13, 95% CI 1.06-4.29) higher than that of the FAS -670AA genotype alone (OR 1.70, 95% CI 1.07-2.70). Conclusions. The FAS -1377A/-670A haplotype in combination with FASL -844C is associated with cervical carcinogenesis.

Original languageEnglish
Pages (from-to)113-118
Number of pages6
JournalGynecologic Oncology
Volume99
Issue number1
DOIs
Publication statusPublished - Oct 2005
Externally publishedYes

Fingerprint

Fas Ligand Protein
Genetic Polymorphisms
Haplotypes
Squamous Cell Carcinoma
Carcinogenesis
Genotype
Papillomavirus Infections
Genes
Alleles
Ligands
Real-Time Polymerase Chain Reaction
Squamous Intraepithelial Lesions of the Cervix
Apoptosis
Neoplasms

Keywords

  • Cervical cancer
  • FAS
  • FASL
  • Gene-gene interaction
  • Haplotype
  • Polymorphism

ASJC Scopus subject areas

  • Obstetrics and Gynaecology
  • Oncology

Cite this

Genetic polymorphisms of FAS and FASL (CD95/CD95L) genes in cervical carcinogenesis : An analysis of haplotype and gene-gene interaction. / Lai, Hung Cheng; Lin, Wei Yu; Lin, Ya Wen; Chang, Cheng Chang; Yu, Mu Hsien; Chen, Chia Chi; Chu, Tang Yuan.

In: Gynecologic Oncology, Vol. 99, No. 1, 10.2005, p. 113-118.

Research output: Contribution to journalArticle

Lai, Hung Cheng ; Lin, Wei Yu ; Lin, Ya Wen ; Chang, Cheng Chang ; Yu, Mu Hsien ; Chen, Chia Chi ; Chu, Tang Yuan. / Genetic polymorphisms of FAS and FASL (CD95/CD95L) genes in cervical carcinogenesis : An analysis of haplotype and gene-gene interaction. In: Gynecologic Oncology. 2005 ; Vol. 99, No. 1. pp. 113-118.
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abstract = "Objective. Whereas human papillomavirus (HPV) infection is necessary but not sufficient for cervical carcinogenesis, host genetic variations may confer individual susceptibility. Resistance to apoptosis is a hallmark of cancer in which FAS/FAS ligand signaling plays an important role. The present study examines the hypothesis that genetic polymorphisms in FAS and FAS ligand genes, alone or in combination, are associated with cervical carcinogenesis. Methods. The genotypes of FAS -670A/G, FAS -1377G/A, and FASL -844C/T were assessed in 143 patients with high-grade squamous intraepithelial lesions (HSIL), 175 patients with invasive squamous cell carcinomas (SCC), and in age-matched controls by real-time PCR with allele-specific TaqMan probes. The status of cervical high-risk HPV infection was determined and adjusted to test the independence of genotype in the risk assessment. Results. The A-allele and AA-genotype frequencies of FASA -670G were significantly higher in HSIL/SCC than in controls (60{\%} vs. 54{\%}, P = 0.04, OR 1.26 [95{\%} CI 1.01-1.57]; 38.0{\%} vs. 28.6{\%}, P = 0.02, OR 1.70 [95{\%} CI 1.07-2.70]). No association between FAS -1377 or FASL -844 polymorphisms and HSIL/SCC could be identified. The FAS -1377A/-670A haplotype conferred a higher risk for HSIL/SCC (OR 3.05, 95{\%} CI 1.28-7.30) than FAS -670A alone (OR 1.26, 95{\%} CI 1.28-7.30). The interaction between FAS -670AA and FASL -844CC genotypes was associated with a risk of HSIL/SCC (OR 2.13, 95{\%} CI 1.06-4.29) higher than that of the FAS -670AA genotype alone (OR 1.70, 95{\%} CI 1.07-2.70). Conclusions. The FAS -1377A/-670A haplotype in combination with FASL -844C is associated with cervical carcinogenesis.",
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T1 - Genetic polymorphisms of FAS and FASL (CD95/CD95L) genes in cervical carcinogenesis

T2 - An analysis of haplotype and gene-gene interaction

AU - Lai, Hung Cheng

AU - Lin, Wei Yu

AU - Lin, Ya Wen

AU - Chang, Cheng Chang

AU - Yu, Mu Hsien

AU - Chen, Chia Chi

AU - Chu, Tang Yuan

PY - 2005/10

Y1 - 2005/10

N2 - Objective. Whereas human papillomavirus (HPV) infection is necessary but not sufficient for cervical carcinogenesis, host genetic variations may confer individual susceptibility. Resistance to apoptosis is a hallmark of cancer in which FAS/FAS ligand signaling plays an important role. The present study examines the hypothesis that genetic polymorphisms in FAS and FAS ligand genes, alone or in combination, are associated with cervical carcinogenesis. Methods. The genotypes of FAS -670A/G, FAS -1377G/A, and FASL -844C/T were assessed in 143 patients with high-grade squamous intraepithelial lesions (HSIL), 175 patients with invasive squamous cell carcinomas (SCC), and in age-matched controls by real-time PCR with allele-specific TaqMan probes. The status of cervical high-risk HPV infection was determined and adjusted to test the independence of genotype in the risk assessment. Results. The A-allele and AA-genotype frequencies of FASA -670G were significantly higher in HSIL/SCC than in controls (60% vs. 54%, P = 0.04, OR 1.26 [95% CI 1.01-1.57]; 38.0% vs. 28.6%, P = 0.02, OR 1.70 [95% CI 1.07-2.70]). No association between FAS -1377 or FASL -844 polymorphisms and HSIL/SCC could be identified. The FAS -1377A/-670A haplotype conferred a higher risk for HSIL/SCC (OR 3.05, 95% CI 1.28-7.30) than FAS -670A alone (OR 1.26, 95% CI 1.28-7.30). The interaction between FAS -670AA and FASL -844CC genotypes was associated with a risk of HSIL/SCC (OR 2.13, 95% CI 1.06-4.29) higher than that of the FAS -670AA genotype alone (OR 1.70, 95% CI 1.07-2.70). Conclusions. The FAS -1377A/-670A haplotype in combination with FASL -844C is associated with cervical carcinogenesis.

AB - Objective. Whereas human papillomavirus (HPV) infection is necessary but not sufficient for cervical carcinogenesis, host genetic variations may confer individual susceptibility. Resistance to apoptosis is a hallmark of cancer in which FAS/FAS ligand signaling plays an important role. The present study examines the hypothesis that genetic polymorphisms in FAS and FAS ligand genes, alone or in combination, are associated with cervical carcinogenesis. Methods. The genotypes of FAS -670A/G, FAS -1377G/A, and FASL -844C/T were assessed in 143 patients with high-grade squamous intraepithelial lesions (HSIL), 175 patients with invasive squamous cell carcinomas (SCC), and in age-matched controls by real-time PCR with allele-specific TaqMan probes. The status of cervical high-risk HPV infection was determined and adjusted to test the independence of genotype in the risk assessment. Results. The A-allele and AA-genotype frequencies of FASA -670G were significantly higher in HSIL/SCC than in controls (60% vs. 54%, P = 0.04, OR 1.26 [95% CI 1.01-1.57]; 38.0% vs. 28.6%, P = 0.02, OR 1.70 [95% CI 1.07-2.70]). No association between FAS -1377 or FASL -844 polymorphisms and HSIL/SCC could be identified. The FAS -1377A/-670A haplotype conferred a higher risk for HSIL/SCC (OR 3.05, 95% CI 1.28-7.30) than FAS -670A alone (OR 1.26, 95% CI 1.28-7.30). The interaction between FAS -670AA and FASL -844CC genotypes was associated with a risk of HSIL/SCC (OR 2.13, 95% CI 1.06-4.29) higher than that of the FAS -670AA genotype alone (OR 1.70, 95% CI 1.07-2.70). Conclusions. The FAS -1377A/-670A haplotype in combination with FASL -844C is associated with cervical carcinogenesis.

KW - Cervical cancer

KW - FAS

KW - FASL

KW - Gene-gene interaction

KW - Haplotype

KW - Polymorphism

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