Common Genetic Variation in TP53 and Risk of Human Papillomavirus Persistence and Progression to CIN3/Cancer Revisited

Abstract

Driven by findings that human papillomavirus (HPV)-induced degradation of p53 differs by a TP53 polymorphism at codon 72 (Pro72Arg), past studies of TP53 genetic variants and cervical cancer have focused on this nonsynonymous polymorphism, with mixed results. We analyzed common single nucleotide polymorphisms (SNP) across the TP53 locus in a population-based nested case-control study in Guanacaste, Costa Rica. We evaluated 11 SNPs, including Pro72Arg (rs1042522), among 1,281 women: 465 with cervical intraepithelial neoplasia grade 3/cancer (CIN3+), 380 with HPV persistence (median, 25 months), and 436 random population controls. We combined HPV persistence and CIN3+ into one case group because they did not differ in TP53 genotypic frequencies and calculated odds ratios and 95% confidence intervals (CI) for individual SNPs and inferred haplotypes. We observed that proline at codon 72 was associated with increased risk of CIN3+/persistence compared with population controls. Relative to GG (Arg), the CG (Pro/Arg) and CC (Pro) genotypes had a 1.3-fold (95% CI, 0.99-1.6) and 1.8-fold (95% CI, 1.2-2.7) increased risk, respectively (P trend < 0.01). rs12951053 and rs1642785 were also associated with CIN3+/persistence (P trend , 0.05 and 0.04, respectively), as was a haplotype containing the codon 72 variant (rs1042522), rs12951053, rs1642785, and rs12947788 (odds ratio, 1.6; 95% CI, 1.1-2.3 versus the most common haplotype, which comprised the major alleles for all 11 SNPs). Although genetic variation in TP53 might affect the natural history of HPV and cervical cancer, further work is needed to elucidate the possible mechanism. (Cancer Epidemiol Biomarkers Prev 2009;18(5):1631 -7)

Polymorphisms in TP53 (rs1042522), p16 (rs11515 and rs3088440) and NQO1 (rs1800566) Genes in Thai Cervical Cancer Patients with HPV 16 Infection

“…Based on previous studies, the Arg polymorphism depends on the population group (Jee et al, 2004;Koushik et al, 2004;Piña-Sánchez et al, 2011). Moreover, a meta-analysis conducted between 1998 and 2002 suggested that any effect is a slightly increased risk associated with arginine at codon 72 (Koshiol et al, 2009). The homozygous Arg are associated with high risk of invasive cervical cancer with OR nearly 1.1-1.2 while studies conducted in most European countries have not observed any significant association (Jee et al, 2004;Koushik et al, 2004;Sousa et al, 2007;Piña-Sánchez et al, 2011;Koshiol et al, 2009).…”

“…Moreover, a meta-analysis conducted between 1998 and 2002 suggested that any effect is a slightly increased risk associated with arginine at codon 72 (Koshiol et al, 2009). The homozygous Arg are associated with high risk of invasive cervical cancer with OR nearly 1.1-1.2 while studies conducted in most European countries have not observed any significant association (Jee et al, 2004;Koushik et al, 2004;Sousa et al, 2007;Piña-Sánchez et al, 2011;Koshiol et al, 2009). However, other biological factors in conjunction with p53 also have an effect on the population.…”

p53 Arg72Pro Polymorphism, HPV Status and Initiation, Progression, and Development of Cervical Cancer: A Systematic Review and Meta-Analysis

“…1). Although there is little data to support or refute the role of the Arg72Pro polymorphism with HPV persistence (22,23), initiation of carcinogenesis is probably independent of this p53 polymorphism because the level of E6 and E7 expression in the basal cells of both SIL and healthy controls is relatively low (24). Moreover, most women who contract high-risk HPV will spontaneously clear the infection with no clinical sequelae (25).…”

Detection of p53 Common Intron Polymorphisms in Patients with Gastritis Lesions from Iran

“…The 16 bp insertion in intron 3 of p53 (p53Ins3) found to be associated with increased risk of several cancers such as colorectal (Gemignani et al, 2003), lung (Wu, et al, 2002), breast (Wang-Gohrke et al, 2002;Koshiol et al, 2009), cervical (Koshiol et al, 2009) and ovary cancer (Angelopoulou et al, 1998;Wang-Gohrke et al, 1999). According to our study most of patients had no insertion while the other was prominently heterozygous.…”

“…Currently, we have no explanation about the probable cause and consequence of this correlation. However, previous work on the cervical cancer revealed that this polymorphism is associated with increased risk of cervical intraepithelial neoplasia/HPV persistence (Koshiol et al, 2009). Also, significant differences were found among the distributions of the genotypes in blood samples compared to the corresponding ovarian cancer tissue (Maunakea et al 2010).…”