Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer

Mahboobeh Safaeian, Allan Hildesheim, Paula Gonzalez, Kai Yu, Carolina Porras, Qizhai Li, Ana Cecilia Rodriguez, Mark E. Sherman, Mark Schiffman, Sholom Wacholder, Robert D. Burk, Rolando Herrero, Laurie Burdette, Stephen J. Chanock, Sophia S. Wang

Research output: Contribution to journalArticle

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Abstract

Background: Host genetic factors might affect the risk of progression from infection with carcinogenic human papillomavirus (HPV), the etiologic agent for cervical cancer, to persistent HPV infection, and hence to cervical precancer and cancer. Methodology/Principal Findings: We assessed 18,310 tag single nucleotide polymorphisms (SNPs) from 1113 genes in 416 cervical intraepithelial neoplasia 3 (CIN3)/cancer cases, 356 women with persistent carcinogenic HPV infection (median persistence of 25 months) and 425 randomly selected women (non-cases and non-HPV persistent) from the 10,049 women from the Guanacaste, Costa Rica HPV natural history cohort. For gene and SNP associations, we computed age-adjusted odds ratio and p-trend. Three comparisons were made: 1) association with CIN3/cancer (compared CIN3/cancer cases to random controls), 2) association with persistence (compared HPV persistence to random controls), and 3) progression (compared CIN3/cancers with HPV-persistent group). Regions statistically significantly associated with CIN3/cancer included genes for peroxiredoxin 3 PRDX3, and ribosomal protein S19 RPS19. The single most significant SNPs from each gene associated with CIN3/cancer were PRDX3 rs7082598 (P trend<0.0001), and RPS19 rs2305809 (P trend=0.0007), respectively. Both SNPs were also associated with progression. Conclusions/Significance: These data suggest involvement of two genes, RSP19 and PRDX3, or other SNPs in linkage disequilibrium, with cervical cancer risk. Further investigation showed that they may be involved in both the persistence and progression transition stages. Our results require replication but, if true, suggest a role for ribosomal dysfunction, mitochondrial processes, and/or oxidative stress, or other unknown function of these genes in cervical carcinogenesis.

Original languageEnglish (US)
Article numbere33619
JournalPLoS One
Volume7
Issue number4
DOIs
StatePublished - Apr 9 2012

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Cervical Intraepithelial Neoplasia
uterine cervical neoplasms
Papillomaviridae
Polymorphism
Uterine Cervical Neoplasms
single nucleotide polymorphism
Single Nucleotide Polymorphism
Nucleotides
Genes
neoplasms
Papillomavirus Infections
Neoplasms
Peroxiredoxin III
Association reactions
Costa Rica
Oxidative stress
genes
Neoplasm Genes
Linkage Disequilibrium
Natural History

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Safaeian, M., Hildesheim, A., Gonzalez, P., Yu, K., Porras, C., Li, Q., ... Wang, S. S. (2012). Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer. PLoS One, 7(4), [e33619]. https://doi.org/10.1371/journal.pone.0033619

Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer. / Safaeian, Mahboobeh; Hildesheim, Allan; Gonzalez, Paula; Yu, Kai; Porras, Carolina; Li, Qizhai; Rodriguez, Ana Cecilia; Sherman, Mark E.; Schiffman, Mark; Wacholder, Sholom; Burk, Robert D.; Herrero, Rolando; Burdette, Laurie; Chanock, Stephen J.; Wang, Sophia S.

In: PLoS One, Vol. 7, No. 4, e33619, 09.04.2012.

Research output: Contribution to journalArticle

Safaeian, M, Hildesheim, A, Gonzalez, P, Yu, K, Porras, C, Li, Q, Rodriguez, AC, Sherman, ME, Schiffman, M, Wacholder, S, Burk, RD, Herrero, R, Burdette, L, Chanock, SJ & Wang, SS 2012, 'Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer', PLoS One, vol. 7, no. 4, e33619. https://doi.org/10.1371/journal.pone.0033619
Safaeian, Mahboobeh ; Hildesheim, Allan ; Gonzalez, Paula ; Yu, Kai ; Porras, Carolina ; Li, Qizhai ; Rodriguez, Ana Cecilia ; Sherman, Mark E. ; Schiffman, Mark ; Wacholder, Sholom ; Burk, Robert D. ; Herrero, Rolando ; Burdette, Laurie ; Chanock, Stephen J. ; Wang, Sophia S. / Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer. In: PLoS One. 2012 ; Vol. 7, No. 4.
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abstract = "Background: Host genetic factors might affect the risk of progression from infection with carcinogenic human papillomavirus (HPV), the etiologic agent for cervical cancer, to persistent HPV infection, and hence to cervical precancer and cancer. Methodology/Principal Findings: We assessed 18,310 tag single nucleotide polymorphisms (SNPs) from 1113 genes in 416 cervical intraepithelial neoplasia 3 (CIN3)/cancer cases, 356 women with persistent carcinogenic HPV infection (median persistence of 25 months) and 425 randomly selected women (non-cases and non-HPV persistent) from the 10,049 women from the Guanacaste, Costa Rica HPV natural history cohort. For gene and SNP associations, we computed age-adjusted odds ratio and p-trend. Three comparisons were made: 1) association with CIN3/cancer (compared CIN3/cancer cases to random controls), 2) association with persistence (compared HPV persistence to random controls), and 3) progression (compared CIN3/cancers with HPV-persistent group). Regions statistically significantly associated with CIN3/cancer included genes for peroxiredoxin 3 PRDX3, and ribosomal protein S19 RPS19. The single most significant SNPs from each gene associated with CIN3/cancer were PRDX3 rs7082598 (P trend<0.0001), and RPS19 rs2305809 (P trend=0.0007), respectively. Both SNPs were also associated with progression. Conclusions/Significance: These data suggest involvement of two genes, RSP19 and PRDX3, or other SNPs in linkage disequilibrium, with cervical cancer risk. Further investigation showed that they may be involved in both the persistence and progression transition stages. Our results require replication but, if true, suggest a role for ribosomal dysfunction, mitochondrial processes, and/or oxidative stress, or other unknown function of these genes in cervical carcinogenesis.",
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AU - Safaeian, Mahboobeh

AU - Hildesheim, Allan

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AU - Yu, Kai

AU - Porras, Carolina

AU - Li, Qizhai

AU - Rodriguez, Ana Cecilia

AU - Sherman, Mark E.

AU - Schiffman, Mark

AU - Wacholder, Sholom

AU - Burk, Robert D.

AU - Herrero, Rolando

AU - Burdette, Laurie

AU - Chanock, Stephen J.

AU - Wang, Sophia S.

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