TY - JOUR
T1 - Single nucleotide polymorphisms in the PRDX3 and RPS19 and risk of HPV persistence and cervical precancer/cancer
AU - Safaeian, Mahboobeh
AU - Hildesheim, Allan
AU - Gonzalez, Paula
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
AU - Herrero, Rolando
AU - Burdette, Laurie
AU - Chanock, Stephen J.
AU - Wang, Sophia S.
N1 - Funding Information:
Laurie Burdette and Stephen J. Chanock are employed by The Core Genotyping Facility (CGF) which is within the Division of Cancer Epidemiology and Genetics (DCEG) of the National Cancer Institute (NCI) and supported by SAIC-Frederick Inc. Information Management Services, Inc. also supported this study, along with Amy Hutchinson and Belynda Hicks with their management of this genotyping effort at the NCI Core Genotyping Facility and for their scientific contributions to the authors' research efforts. This does not alter the authors' adherence to all PloS ONE policies on sharing data and materials.
PY - 2012/4/9
Y1 - 2012/4/9
N2 - 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.
AB - 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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U2 - 10.1371/journal.pone.0033619
DO - 10.1371/journal.pone.0033619
M3 - Article
C2 - 22496757
AN - SCOPUS:84859509236
SN - 1932-6203
VL - 7
JO - PloS one
JF - PloS one
IS - 4
M1 - e33619
ER -