Abstract
BackgroundHost 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 FindingsWe 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/SignificanceThese 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.
Highlights
While it is well-known that carcinogenic human papillomaviruses (HPVs) are the causal agents of cervical cancer, HPV infections are extremely common relative to rare cancer incidence, indicating that many infections spontaneously resolve [1], or persist without progression
Host genetic factors may play a role in cervical carcinogenesis and are thought to influence who develops persistent HPV infection and perhaps who further progresses to cancer [2,3,4,5,6,7]
Of the genes identified to be associated with CIN3/cancer RPS19 was associated with progression to CIN3/cancer (p-value 0.006)
Summary
While it is well-known that carcinogenic human papillomaviruses (HPVs) are the causal agents of cervical cancer, HPV infections are extremely common relative to rare cancer incidence, indicating that many infections spontaneously resolve [1], or persist without progression. Host genetic factors may play a role in cervical carcinogenesis and are thought to influence who develops persistent HPV infection and perhaps who further progresses to cancer [2,3,4,5,6,7]. 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 to cervical precancer and cancer
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