Host genetic polymorphism analysis in cervical cancer

Eric S. Calhoun, Renee M. McGovern, Carol A. Janney, James R Cerhan, Stephen J. Iturria, David I Smith, Bobbie S. Gostout, David H. Persing

Research output: Contribution to journalArticle

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Abstract

Background: The natural history of cervical cancer comprises a latency period that probably involves long-term immunologic tolerance of human papillomavirus infection. Identifying host determinants of viral persistence may help to better understand the mechanisms of tolerance and may lead to the development of tests that can allow more focused follow-up of high-risk individuals. Methods: Genotypic frequencies of 12 polymorphic loci in four candidate genes from 127 Cervical cancer patients were compared with a control group of 108 female blood donors. Genotypes were determined by PCR amplification and direct sequencing of isolated genomic DNA. Results: The tumor necrosis factor-α (TNFα) -238 polymorphism was significantly underrepresented in cervical cancer patients [heterozygotes (HETs), odds ratio (OR) = 0.33; 95% confidence interval (CI), 0.11-0.96], as was the TNFα -376 polymorphism (P = 0.02; 0% for any variant genotype in cases vs 4.7% in controls). The NRAMP1 3′ untranslated region STP+86 polymorphism also appeared to be inversely associated with cervical cancer, but this result did not reach statistical significance (HET, OR = 0.57; 95% CI, 0.32-1.02). The p53 codon 72 arginine allele showed a suggestive negative association with cervical cancer (HET, OR = 0.49; 95% CI, 0.14-1.63; homozygotes, OR = 0.35; 95% CI, 0.11-1.17). The remaining alleles tested showed no association with cervical cancer. Conclusions: We identified host genetic polymorphisms that may be associated with cervical cancer risk, some of which have been linked to potential functional effects on cellular immune responses or antigen processing. We failed to confirm earlier reports of increased cervical cancer susceptibility in women who harbor the p53 P72R allele. Although our findings support the general hypothesis that host immunogenetic determinants other than class II MHC may be important in the development of cervical cancer, further analysis of the HLA gene cluster comprising the implicated TNFα single-nucleotide polymorphisms will be required to determine whether their association is linkage independent.

Original languageEnglish (US)
Pages (from-to)1218-1224
Number of pages7
JournalClinical Chemistry
Volume48
Issue number8
StatePublished - 2002
Externally publishedYes

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Genetic Polymorphisms
Polymorphism
Uterine Cervical Neoplasms
Tumor Necrosis Factor-alpha
Heterozygote
Odds Ratio
Confidence Intervals
Genes
Alleles
3' Untranslated Regions
Ports and harbors
Amplification
Arginine
Genotype
Blood
Nucleotides
Immunogenetics
Papillomavirus Infections
Antigens
Histocompatibility Antigens Class II

ASJC Scopus subject areas

  • Clinical Biochemistry

Cite this

Calhoun, E. S., McGovern, R. M., Janney, C. A., Cerhan, J. R., Iturria, S. J., Smith, D. I., ... Persing, D. H. (2002). Host genetic polymorphism analysis in cervical cancer. Clinical Chemistry, 48(8), 1218-1224.

Host genetic polymorphism analysis in cervical cancer. / Calhoun, Eric S.; McGovern, Renee M.; Janney, Carol A.; Cerhan, James R; Iturria, Stephen J.; Smith, David I; Gostout, Bobbie S.; Persing, David H.

In: Clinical Chemistry, Vol. 48, No. 8, 2002, p. 1218-1224.

Research output: Contribution to journalArticle

Calhoun, ES, McGovern, RM, Janney, CA, Cerhan, JR, Iturria, SJ, Smith, DI, Gostout, BS & Persing, DH 2002, 'Host genetic polymorphism analysis in cervical cancer', Clinical Chemistry, vol. 48, no. 8, pp. 1218-1224.
Calhoun ES, McGovern RM, Janney CA, Cerhan JR, Iturria SJ, Smith DI et al. Host genetic polymorphism analysis in cervical cancer. Clinical Chemistry. 2002;48(8):1218-1224.
Calhoun, Eric S. ; McGovern, Renee M. ; Janney, Carol A. ; Cerhan, James R ; Iturria, Stephen J. ; Smith, David I ; Gostout, Bobbie S. ; Persing, David H. / Host genetic polymorphism analysis in cervical cancer. In: Clinical Chemistry. 2002 ; Vol. 48, No. 8. pp. 1218-1224.
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abstract = "Background: The natural history of cervical cancer comprises a latency period that probably involves long-term immunologic tolerance of human papillomavirus infection. Identifying host determinants of viral persistence may help to better understand the mechanisms of tolerance and may lead to the development of tests that can allow more focused follow-up of high-risk individuals. Methods: Genotypic frequencies of 12 polymorphic loci in four candidate genes from 127 Cervical cancer patients were compared with a control group of 108 female blood donors. Genotypes were determined by PCR amplification and direct sequencing of isolated genomic DNA. Results: The tumor necrosis factor-α (TNFα) -238 polymorphism was significantly underrepresented in cervical cancer patients [heterozygotes (HETs), odds ratio (OR) = 0.33; 95{\%} confidence interval (CI), 0.11-0.96], as was the TNFα -376 polymorphism (P = 0.02; 0{\%} for any variant genotype in cases vs 4.7{\%} in controls). The NRAMP1 3′ untranslated region STP+86 polymorphism also appeared to be inversely associated with cervical cancer, but this result did not reach statistical significance (HET, OR = 0.57; 95{\%} CI, 0.32-1.02). The p53 codon 72 arginine allele showed a suggestive negative association with cervical cancer (HET, OR = 0.49; 95{\%} CI, 0.14-1.63; homozygotes, OR = 0.35; 95{\%} CI, 0.11-1.17). The remaining alleles tested showed no association with cervical cancer. Conclusions: We identified host genetic polymorphisms that may be associated with cervical cancer risk, some of which have been linked to potential functional effects on cellular immune responses or antigen processing. We failed to confirm earlier reports of increased cervical cancer susceptibility in women who harbor the p53 P72R allele. Although our findings support the general hypothesis that host immunogenetic determinants other than class II MHC may be important in the development of cervical cancer, further analysis of the HLA gene cluster comprising the implicated TNFα single-nucleotide polymorphisms will be required to determine whether their association is linkage independent.",
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T1 - Host genetic polymorphism analysis in cervical cancer

AU - Calhoun, Eric S.

AU - McGovern, Renee M.

AU - Janney, Carol A.

AU - Cerhan, James R

AU - Iturria, Stephen J.

AU - Smith, David I

AU - Gostout, Bobbie S.

AU - Persing, David H.

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N2 - Background: The natural history of cervical cancer comprises a latency period that probably involves long-term immunologic tolerance of human papillomavirus infection. Identifying host determinants of viral persistence may help to better understand the mechanisms of tolerance and may lead to the development of tests that can allow more focused follow-up of high-risk individuals. Methods: Genotypic frequencies of 12 polymorphic loci in four candidate genes from 127 Cervical cancer patients were compared with a control group of 108 female blood donors. Genotypes were determined by PCR amplification and direct sequencing of isolated genomic DNA. Results: The tumor necrosis factor-α (TNFα) -238 polymorphism was significantly underrepresented in cervical cancer patients [heterozygotes (HETs), odds ratio (OR) = 0.33; 95% confidence interval (CI), 0.11-0.96], as was the TNFα -376 polymorphism (P = 0.02; 0% for any variant genotype in cases vs 4.7% in controls). The NRAMP1 3′ untranslated region STP+86 polymorphism also appeared to be inversely associated with cervical cancer, but this result did not reach statistical significance (HET, OR = 0.57; 95% CI, 0.32-1.02). The p53 codon 72 arginine allele showed a suggestive negative association with cervical cancer (HET, OR = 0.49; 95% CI, 0.14-1.63; homozygotes, OR = 0.35; 95% CI, 0.11-1.17). The remaining alleles tested showed no association with cervical cancer. Conclusions: We identified host genetic polymorphisms that may be associated with cervical cancer risk, some of which have been linked to potential functional effects on cellular immune responses or antigen processing. We failed to confirm earlier reports of increased cervical cancer susceptibility in women who harbor the p53 P72R allele. Although our findings support the general hypothesis that host immunogenetic determinants other than class II MHC may be important in the development of cervical cancer, further analysis of the HLA gene cluster comprising the implicated TNFα single-nucleotide polymorphisms will be required to determine whether their association is linkage independent.

AB - Background: The natural history of cervical cancer comprises a latency period that probably involves long-term immunologic tolerance of human papillomavirus infection. Identifying host determinants of viral persistence may help to better understand the mechanisms of tolerance and may lead to the development of tests that can allow more focused follow-up of high-risk individuals. Methods: Genotypic frequencies of 12 polymorphic loci in four candidate genes from 127 Cervical cancer patients were compared with a control group of 108 female blood donors. Genotypes were determined by PCR amplification and direct sequencing of isolated genomic DNA. Results: The tumor necrosis factor-α (TNFα) -238 polymorphism was significantly underrepresented in cervical cancer patients [heterozygotes (HETs), odds ratio (OR) = 0.33; 95% confidence interval (CI), 0.11-0.96], as was the TNFα -376 polymorphism (P = 0.02; 0% for any variant genotype in cases vs 4.7% in controls). The NRAMP1 3′ untranslated region STP+86 polymorphism also appeared to be inversely associated with cervical cancer, but this result did not reach statistical significance (HET, OR = 0.57; 95% CI, 0.32-1.02). The p53 codon 72 arginine allele showed a suggestive negative association with cervical cancer (HET, OR = 0.49; 95% CI, 0.14-1.63; homozygotes, OR = 0.35; 95% CI, 0.11-1.17). The remaining alleles tested showed no association with cervical cancer. Conclusions: We identified host genetic polymorphisms that may be associated with cervical cancer risk, some of which have been linked to potential functional effects on cellular immune responses or antigen processing. We failed to confirm earlier reports of increased cervical cancer susceptibility in women who harbor the p53 P72R allele. Although our findings support the general hypothesis that host immunogenetic determinants other than class II MHC may be important in the development of cervical cancer, further analysis of the HLA gene cluster comprising the implicated TNFα single-nucleotide polymorphisms will be required to determine whether their association is linkage independent.

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