Common variants in immune and DNA repair genes and risk for human papillomavirus persistence and progression to cervical cancer

Sophia S. Wang, M. Concepcion Bratti, Ana Cecilia Rodríguez, Rolando Herrero, Robert D. Burk, Carolina Porras, Paula González, Mark E. Sherman, Sholom Wacholder, Z. Elizabeth Lan, Mark Schiffman, Stephen J. Chanock, Allan Hildesheim

Research output: Contribution to journalArticle

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Abstract

Background. We examined host genetic factors to identify those more common in individuals whose human papillomavirus (HPV) infections were most likely to persist and progress to cervical intraepithelial neoplasia grade 3 (CIN3) and cancer. Methods. We genotyped 92 single-nucleotide polymorphisms (SNPs) from 49 candidate immune response and DNA repair genes obtained from 469 women with CIN3 or cancer, 390 women with persistent HPV infections (median duration, 25 months), and 452 random control subjects from the 10,049-woman Guanacaste Costa Rica Natural History Study. We calculated odds ratios and 95% confidence intervals (CIs) for the association of SNP and haplotypes in women with CIN3 or cancer and HPV persistence, compared with random control subjects. Results. A SNP in the Fanconi anemia complementation group A gene (FANCA) (G501S) was associated with increased risk of CIN3 or cancer. The AG and GG genotypes had a 1.3-fold (95% CI, 0.95-1.8-fold) and 1.7-fold (95% CI, 1.1-2.6-fold) increased risk for CIN3 or cancer, respectively (Ptrend = .008; referent, AA). The FANCA haplotype that included G501S also conferred increased risk of CIN3 or cancer, as did a different haplotype that included 2 other FANCA SNPs (G809A and T266A). A SNP in the innate immune gene IRF3 (S427T) was associated with increased risk for HPV persistence (Ptrend = .009). Conclusions. Our results require replication but support the role of FANCA variants in cervical cancer susceptibility and of IRF3 in HPV persistence.

Original languageEnglish (US)
Pages (from-to)20-30
Number of pages11
JournalJournal of Infectious Diseases
Volume199
Issue number1
DOIs
StatePublished - Jan 1 2009

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Cervical Intraepithelial Neoplasia
DNA Repair
Uterine Cervical Neoplasms
Fanconi Anemia
Single Nucleotide Polymorphism
Haplotypes
Genes
Neoplasms
Papillomavirus Infections
Confidence Intervals
Costa Rica
Natural History
Odds Ratio
Genotype

ASJC Scopus subject areas

  • Infectious Diseases
  • Immunology and Allergy

Cite this

Common variants in immune and DNA repair genes and risk for human papillomavirus persistence and progression to cervical cancer. / Wang, Sophia S.; Bratti, M. Concepcion; Rodríguez, Ana Cecilia; Herrero, Rolando; Burk, Robert D.; Porras, Carolina; González, Paula; Sherman, Mark E.; Wacholder, Sholom; Lan, Z. Elizabeth; Schiffman, Mark; Chanock, Stephen J.; Hildesheim, Allan.

In: Journal of Infectious Diseases, Vol. 199, No. 1, 01.01.2009, p. 20-30.

Research output: Contribution to journalArticle

Wang, SS, Bratti, MC, Rodríguez, AC, Herrero, R, Burk, RD, Porras, C, González, P, Sherman, ME, Wacholder, S, Lan, ZE, Schiffman, M, Chanock, SJ & Hildesheim, A 2009, 'Common variants in immune and DNA repair genes and risk for human papillomavirus persistence and progression to cervical cancer', Journal of Infectious Diseases, vol. 199, no. 1, pp. 20-30. https://doi.org/10.1086/595563
Wang, Sophia S. ; Bratti, M. Concepcion ; Rodríguez, Ana Cecilia ; Herrero, Rolando ; Burk, Robert D. ; Porras, Carolina ; González, Paula ; Sherman, Mark E. ; Wacholder, Sholom ; Lan, Z. Elizabeth ; Schiffman, Mark ; Chanock, Stephen J. ; Hildesheim, Allan. / Common variants in immune and DNA repair genes and risk for human papillomavirus persistence and progression to cervical cancer. In: Journal of Infectious Diseases. 2009 ; Vol. 199, No. 1. pp. 20-30.
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T1 - Common variants in immune and DNA repair genes and risk for human papillomavirus persistence and progression to cervical cancer

AU - Wang, Sophia S.

AU - Bratti, M. Concepcion

AU - Rodríguez, Ana Cecilia

AU - Herrero, Rolando

AU - Burk, Robert D.

AU - Porras, Carolina

AU - González, Paula

AU - Sherman, Mark E.

AU - Wacholder, Sholom

AU - Lan, Z. Elizabeth

AU - Schiffman, Mark

AU - Chanock, Stephen J.

AU - Hildesheim, Allan

PY - 2009/1/1

Y1 - 2009/1/1

N2 - Background. We examined host genetic factors to identify those more common in individuals whose human papillomavirus (HPV) infections were most likely to persist and progress to cervical intraepithelial neoplasia grade 3 (CIN3) and cancer. Methods. We genotyped 92 single-nucleotide polymorphisms (SNPs) from 49 candidate immune response and DNA repair genes obtained from 469 women with CIN3 or cancer, 390 women with persistent HPV infections (median duration, 25 months), and 452 random control subjects from the 10,049-woman Guanacaste Costa Rica Natural History Study. We calculated odds ratios and 95% confidence intervals (CIs) for the association of SNP and haplotypes in women with CIN3 or cancer and HPV persistence, compared with random control subjects. Results. A SNP in the Fanconi anemia complementation group A gene (FANCA) (G501S) was associated with increased risk of CIN3 or cancer. The AG and GG genotypes had a 1.3-fold (95% CI, 0.95-1.8-fold) and 1.7-fold (95% CI, 1.1-2.6-fold) increased risk for CIN3 or cancer, respectively (Ptrend = .008; referent, AA). The FANCA haplotype that included G501S also conferred increased risk of CIN3 or cancer, as did a different haplotype that included 2 other FANCA SNPs (G809A and T266A). A SNP in the innate immune gene IRF3 (S427T) was associated with increased risk for HPV persistence (Ptrend = .009). Conclusions. Our results require replication but support the role of FANCA variants in cervical cancer susceptibility and of IRF3 in HPV persistence.

AB - Background. We examined host genetic factors to identify those more common in individuals whose human papillomavirus (HPV) infections were most likely to persist and progress to cervical intraepithelial neoplasia grade 3 (CIN3) and cancer. Methods. We genotyped 92 single-nucleotide polymorphisms (SNPs) from 49 candidate immune response and DNA repair genes obtained from 469 women with CIN3 or cancer, 390 women with persistent HPV infections (median duration, 25 months), and 452 random control subjects from the 10,049-woman Guanacaste Costa Rica Natural History Study. We calculated odds ratios and 95% confidence intervals (CIs) for the association of SNP and haplotypes in women with CIN3 or cancer and HPV persistence, compared with random control subjects. Results. A SNP in the Fanconi anemia complementation group A gene (FANCA) (G501S) was associated with increased risk of CIN3 or cancer. The AG and GG genotypes had a 1.3-fold (95% CI, 0.95-1.8-fold) and 1.7-fold (95% CI, 1.1-2.6-fold) increased risk for CIN3 or cancer, respectively (Ptrend = .008; referent, AA). The FANCA haplotype that included G501S also conferred increased risk of CIN3 or cancer, as did a different haplotype that included 2 other FANCA SNPs (G809A and T266A). A SNP in the innate immune gene IRF3 (S427T) was associated with increased risk for HPV persistence (Ptrend = .009). Conclusions. Our results require replication but support the role of FANCA variants in cervical cancer susceptibility and of IRF3 in HPV persistence.

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