HPV prevalence and genetic predisposition to cervical cancer in Saudi Arabia

Infectious Agents and Cancer

Ismail Al-Badawi³  Medhat El-Sebaie²  Najla Al-Harbi⁴  Ghazi Alsbeih¹ 

[1] Research Centre, Biomedical Physics Department, KFSHRC, MBC-03, P.O. Box 3354, Riyadh 11211, Saudi Arabia;Radiation Oncology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia;Obstetrics & Gynecology, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia;Biomedical Physics, King Faisal Specialist Hospital & Research Centre, Riyadh, Saudi Arabia

关键词: Single nucleotide polymorphism (SNP);    Predisposition;    Human papillomavirus (HPV);    Cervical cancer;   

Others  :  803094
DOI  :  10.1186/1750-9378-8-15

 received in 2012-12-31, accepted in 2013-04-17,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Alsbeih et al.; BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

Figure 3.

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