Reduced rate of human papillomavirus infection and genetic overtransmission of TP53 72C polymorphic variant lower cervical cancer incidence

Abstract

BACKGROUNDCervical cancer is a predominantly human papillomavirus (HPV)‐driven disease worldwide. However, its incidence is unexplainably low in western Asia, including Saudi Arabia. Using this paradigm, we investigated the role of HPV infection rate and host genetic predisposition in TP53 G72C single nucleotide polymorphism (SNP) presumed to affect cancer incidence.METHODSPatients treated between 1990 and 2012 were reviewed, and a series of 232 invasive cervical cancer cases were studied and compared with 313 matched controls without cancer. SNP was genotyped by way of direct sequencing. HPV linear array analysis was used to detect and genotype HPV in tumor samples.RESULTSThe incidence of cervical cancer revealed bimodal peaks at 42.5 years, with a slighter rebound at 60.8 years. Among all cases, 77% were HPV‐positive and 16 HPV genotypes were detected—mostly genotypes 16 (75%) and 18 (9%)—with no difference by age, histology, or geographical region. Although the TP53 G72C genotype was not associated with overall cervical cancer risk, it was significantly associated with HPV positivity (odds ratio, 0.57; 95% confidence interval, 0.36‐0.90; P = .016). Furthermore, the variant C allele was significantly overtransmitted in the population (P < .0003).CONCLUSIONCervical cancer incidence displays bimodal curve peaking at a young age with secondary rebound at older age. The combination of relative low HPV infection and variant TP53 72C allele overtransmission provide a plausible explanation for the low incidence of cervical cancer in our population. Therefore, HPV screening and host SNP genotyping may provide more relevant biomarkers to gauge the risk of developing cervical cancer. Cancer 2017;123:2459–66. © 2017 The Authors. Cancer published by Wiley Periodicals, Inc. on behalf of American Cancer Society. This is an open access article under the terms of the Creative Commons Attribution NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.

Prevalence of Human Papillomavirus (HPV) Infection and the Association with Survival in Saudi Patients with Head and Neck Squamous Cell Carcinoma

“…Overall, these results imply that the prevalence of HPV-driven HNSCC in our population is very low. The reasons for this low rate is unknown, but could be related to the predominance of other risk factors, such as various tobacco products consumption, which is as high as 62% of patients, socio-cultural differences, or the presence of relative protective variants of genetic predisposing factors as has been shown previously for cervical cancer patients [31]. Most infections (90%) were with HPV16 (9/10) followed by 10% with HPV33 (1/10) genotypes.…”

“…This PCR-based test detects and genotypes the 37 most common anogenital HPVs (13 high-risk: 16, 18, 31, 33, 35, 39, 45, 51, 52, 56, 58, 59, 68, and 24 low-risk: 6, 11, 26, 40, 42, 53, 54, 55, 61, 62, 64, 66, 67, 69, 70, 71, 72, 73 (MM9), 81, 82 (MM4), 83 (MM7), 84 (MM8), 89 (CP6108) and IS39). Procedures followed the manufacture’s instruction described in detail previously [31,49]. Briefly, the methodology involves the PCR amplification of the target DNA, the hybridization of the amplified DNA segments to oligonucleotide probes immobilized on strips of membranes, and finally, the colorimetric detection of the hybridized products using the Linear Array Detection Kit.…”

Elevated serum expression of p53 and association of TP53 codon 72 polymorphisms with risk of cervical cancer in Bangladeshi women

“…These findings have been collaborated with the meta-analysis study which reported that Pro/Pro genotype and proline allele was associated with increased risk of cervical cancer within the Indian population [ 21 ]. On the contrary, the proline allele was found to confer a protective effect in patients with cervical cancer from Saudi Arabia [ 22 ]. The proline allele has also been linked with increased overall survival in Caucasian cervical cancer patients [ 23 ].…”

Interaction between TP53 and XRCC1 increases susceptibility to cervical cancer development: a case control study

“…Recently, numerous studies have been performed to assess the effect of SNPs on cervical cancer susceptibility [11–13]. Based on these reports and findings from bioinformatics studies exploring high risk factors within the Chinese population for cervical cancer, we focused our current study on crucial genes within the DNA repair and recombination pathways.…”