title: Reduced rate of human papillomavirus infection and genetic overtransmission of TP53 72C polymorphic variant lower cervical cancer incidence.
abstract: BACKGROUND
  Cervical 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.
  
  
  METHODS
  Patients 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.
  
  
  RESULTS
  The 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).
  
  
  CONCLUSIONS
  Cervical 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 American Cancer Society.
authors.affiliation: Biomedical Physics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
authors.forename: Ghazi A
authors.identifier: http://orcid.org/0000-0002-2128-6293
authors.initials: GA
authors.lastname: Alsbeih
authors.affiliation: Biomedical Physics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
authors.forename: Najla M
authors.initials: NM
authors.lastname: Al-Harbi
authors.affiliation: Biomedical Physics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
authors.forename: Sara S
authors.initials: SS
authors.lastname: Bin Judia
authors.affiliation: Pathology & Laboratory Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
authors.forename: Hatim A
authors.initials: HA
authors.lastname: Khoja
authors.affiliation: National Biotechnology Centre, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
authors.forename: Mohamed M
authors.initials: MM
authors.lastname: Shoukri
authors.affiliation: Pathology & Laboratory Medicine, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia.
authors.forename: Asma M
authors.initials: AM
authors.lastname: Tulbah
mesh_terms: D000230:Adenocarcinoma / Q000453:epidemiology* / Q000235:genetics / Q000821:virology; D000328:Adult; D017677:Age Distribution; D000368:Aged; D000483:Alleles; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology* / Q000235:genetics / Q000821:virology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D016017:Odds Ratio; D027383:Papillomaviridae; D030361:Papillomavirus Infections / Q000453:epidemiology* / Q000235:genetics / Q000821:virology; D020641:Polymorphism, Single Nucleotide; D012529:Saudi Arabia / Q000453:epidemiology; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*; D002583:Uterine Cervical Neoplasms / Q000453:epidemiology* / Q000235:genetics / Q000821:virology
chemical_list: C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53
keywords: HPV genotyping; TP53 polymorphism; cancer predisposition; cervical cancer; human papillomavirus; single nucleotide polymorphism