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. 2013 May 4;8(1):15.
doi: 10.1186/1750-9378-8-15.

HPV prevalence and genetic predisposition to cervical cancer in Saudi Arabia

Ghazi Alsbeih  1 , Najla Al-Harbi, Medhat El-Sebaie, Ismail Al-Badawi
Affiliations

HPV prevalence and genetic predisposition to cervical cancer in Saudi Arabia

Ghazi Alsbeih et al. Infect Agent Cancer. .

Abstract

Background: Cervical cancer incidence is low in Saudi Arabian women, suggesting low prevalence to HPV infection due to environmental, cultural and genetic differences. Therefore, we investigated HPV prevalence and genotype distribution in cervical cancer as well as the association with 9 genetic single nucleotide polymorphisms (SNPs): CDKN1A (p21) C31A, TP53 C72G, ATM G1853A, HDM2 promoter T309G, HDM2 A110G, LIG4 A591G, XRCC1 G399A, XRCC3 C241T and TGFβ1 T10C, presumed to predispose to cancer.

Methods: One hundred cervical cancer patients (90 squamous cell carcinoma and 10 adenocarcinoma) and 100 age/sex-matched controls were enrolled. SNPs were genotyped by direct sequencing and HPV was detected and typed in tumors using the HPV Linear Array Test.

Results: Eighty-two cases (82%) were positive for HPV sequences. Seven HPV genotypes were present as single infections (16, 18, 31, 45, 56, 59, 73) and five double infections (16/18, 16/39, 16/70, 35/52, 45/59) were detected. Most common genotypes were HPV-16 (71%), 31 (7%), and 18, 45, 73 (4% each). Only XRCC1 SNP was significantly associated with cervical cancer (P=0.02, OD=1.69; 95% CI= 1.06-2.66). However, nested analysis revealed a preponderance of HPV-positivity in patients harboring the presumed risk allele TP53 G (P=0.06). Both XRCC1 and TP53 SNPs tended to deviate from Hardy-Weinberg equilibrium (HWE; P=0.03-0.07).

Conclusions: HPV prevalence (82%) in cervical cancer is at the lower range of the worldwide estimation (85 - 99%). While XRCC1 G399A was significantly associated with cervical cancer, TP53 G72C showed borderline association only in HPV-positive patients. Deviation from HWE in HPV-positive patients indicates co-selection, hence implicating the combination of HPV and SNPs in cancer predisposition. Thus, SNPs could be more relevant biomarkers of susceptibility to cervical cancer when associated with HPV infection.

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Figures

Figure 1
Figure 1
Schematic representation of main pathways involved in processing of genotoxic DNA damage including base damages (BDs), DNA single-strand breaks (SSBs) and double-strand breaks (DSBs). BDs and SSBs are efficiently repaired by base-excision (BER) and SSBR mechanisms. DSBs are repaired by non-homologous end joining (NHEJ) and homologous recombination (HR). These activate panoply of interacting proteins in tissues, cells and mitochondria that lead to the expression and inhibition of multiple genes. These normally results in cell cycle arrest to allow for accurate DNA healing to prevent the cells from entering DNA synthesis with damaged DNA. The aim is to maintain genomic integrity which enables recovery or otherwise triggers cell death. The E6 and E7 oncoproteins produced by high risk HPV infections will respectively interact with TP53 and RB tumor suppressor proteins and inhibit their functions leading to genomic instability. Lines represent interactions. Arrows indicate activation and blunt ends indicate inhibition. Thickness represents the strength of the actions. Underlined text designates encoding genes selected for polymorphic variations predisposing to cervical cancer (See text for details).
Figure 2
Figure 2
The distribution of squamous cell carcinoma and adenocarcinoma by 5-year age group in 100 cervical cancer patients.
Figure 3
Figure 3
The distribution of HPV detection and genotypes by 5-year age group in 100 cervical cancer patients.
See this image and copyright information in PMC

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