TY - JOUR
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
N1 - Funding Information:
This work was supported by the National Cancer Institute Intramural Program and National Institutes of Health (contracts CO-12400, CP-21081, and CP-31061 to R.H.; grant CA-78527 to R.D.B.); FUCODOCSA (Costa Rican Foundation for Training in Health Sciences); Caja Costarricense de Seguro Social (Costa Rica).
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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U2 - 10.1086/595563
DO - 10.1086/595563
M3 - Article
C2 - 19012493
AN - SCOPUS:58749088558
SN - 0022-1899
VL - 199
SP - 20
EP - 30
JO - Journal of Infectious Diseases
JF - Journal of Infectious Diseases
IS - 1
ER -