BackgroundCervical 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.MethodsOne 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.ResultsEighty-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).ConclusionsHPV 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.

Genetic predictive biomarkers of radiosensitivity are being sought to individualize radiation treatment of cancer patients. In this pilot case-control study, we tested the association between TGFB1 T869C codon 10 Leu/Pro (rs1982073), XRCC1 G28152A codon 399 Arg/Gln (rs25487), and XRCC3 C18067T codon 241 Thr/Met (rs861539) single-nucleotide polymorphisms (SNPs) and late reaction to radiotherapy in 60 nasopharyngeal cancer patients. Subcutaneous and deep tissue fibrosis was scored using the RTOG/EORTC grading system. Patients with moderate to severe fibrosis (radiosensitive cases, G2-3, n = 30) were matched and compared to those with little or no reaction (controls, G0-1, n = 30). The three nonsynonymous SNPs were genotyped by direct DNA sequencing. Significant association was observed for TGFB1 T869C and XRCC1 G28152A genotypes (P < or = 0.05). Both variant alleles, TGFB1 869C and XRCC1 28152A, were associated with a lower grade of fibrosis (odds ratios were 0.41, 95% CI: 0.20-0.86, P = 0.02 and 0.30, 95% CI: 0.10-0.89, P = 0.02, respectively), and therefore the wild-types were the risk alleles. Interestingly, there was a significant difference in the median number of risk alleles between the radiosensitive and the control groups (P = 0.006). We conclude that radiotherapy complications are associated with genetic variations in our nasopharynx cancer patients. Our findings support the assumption of the combined effects of multiple SNPs. Large-scale studies are required to confirm these findings before polymorphisms can be used as predictive markers to individualize radiation therapy on genetic bases.

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Head and neck squamous cell carcinoma (HNSCC) shows wide disparities, association with human papillomavirus (HPV) infection, and prognosis. We aimed at determining HPV prevalence, and its prognostic association with overall survival (OS) in Saudi HNSCC patients. The study included 285 oropharyngeal and oral-cavity HNSCC patients. HPV was detected using HPV Linear-Array and RealLine HPV-HCR. In addition, p16INK4a (p16) protein overexpression was evaluated in 50 representative cases. Oropharyngeal cancers were infrequent (10%) compared to oral-cavity cancers (90%) with no gender differences. Overall, HPV-DNA was positive in 10 HNSCC cases (3.5%), mostly oropharyngeal (21%). However, p16 expression was positive in 21 cases of the 50 studied (42%) and showed significantly higher OS (p = 0.02). Kaplan–Meier univariate analysis showed significant associations between patients’ OS and age (p < 0.001), smoking (p = 0.02), and tumor stage (p < 0.001). A Cox proportional hazard multivariate analysis confirmed the significant associations with age, tumor stage, and also treatment (p < 0.01). In conclusion, HPV-DNA prevalence was significantly lower in our HNSCC patients than worldwide 32–36% estimates (p ≤ 0.001). Although infrequent, oropharyngeal cancer increased over years and showed 21% HPV-DNA positivity, which is close to the worldwide 36–46% estimates (p = 0.16). Besides age, smoking, tumor stage, and treatment, HPV/p16 status was an important determinant of patients’ survival. The HPV and/or p16 positivity patients had a better OS than HPV/p16 double-negative patients (p = 0.05). Thus, HPV/p16 status helps improve prognosis by distinguishing between the more favorable p16/HPV positive and the less favorable double-negative tumors.

Although the variation in individual radiosensitivity was associated with certain SNPs, gender bias for both endpoints was evident. Therefore, assessing the risk of radiation exposure in females and males should be considered separately in order to achieve the ultimate goal of personalized radiation medicine.

Aim: Individuals differ in their inherited tendency to develop cancer. This has been suggested to be due to genetic variations between individuals. Single-nucleotide polymorphisms (SNPs) are the most common form of genetic variations found in the human population. The aim of this study was to investigate the association between 10 SNPs in genes involved in cell cycle control and DNA repair (p21 C31A, p53 G72C, ATM G1853A, XRCC1 G399A, XRCC3 C241T, Ku80 A2790G, DNA Ligase IV C9T, DNA-PKcs A3434G, TGF-beta T10C, MDM2 promoter T309G) and the risk to develop head and neck cancer. Materials and Methods: A cohort of 407 individuals (156 cancer patients and 251 controls) was included. DNA was extracted from peripheral blood. SNPs were genotyped by direct sequencing. Results: Data showed significant allelic associations for p21 C31A ( p = 0.04; odds ratio [OR] = 1.44; confidence interval [CI]: 1.02-2.03), Ku80 A2790G ( p = 0.04; OR = 1.5; CI: 1.01-2.23), and MDM2 T309G ( p = 0.0003; OR = 0.58; CI: 0.43-0.78) and head and neck cancer occurrence. Both cancer cases and controls were in Hardy-Weinberg equilibrium. Conclusion: SNPs can be associated with head and neck cancer in the Saudi population. The p21 C31A, Ku80 A2790G, and MDM2 T309G SNPs could be used as genetic biomarkers to screen individuals at high cancer risk.

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BackgroundBiomarkers are needed to individualize cancer radiation treatment. Therefore, we have investigated the association between various risk factors, including single nucleotide polymorphisms (SNPs) in candidate genes and late complications to radiotherapy in our nasopharyngeal cancer patients.MethodsA cohort of 155 patients was included. Normal tissue fibrosis was scored using RTOG/EORTC grading system. A total of 45 SNPs in 11 candidate genes (ATM, XRCC1, XRCC3, XRCC4, XRCC5, PRKDC, LIG4, TP53, HDM2, CDKN1A, TGFB1) were genotyped by direct genomic DNA sequencing. Patients with severe fibrosis (cases, G3-4, n = 48) were compared to controls (G0-2, n = 107).ResultsUnivariate analysis showed significant association (P < 0.05) with radiation complications for 6 SNPs (ATM G/A rs1801516, HDM2 promoter T/G rs2279744 and T/A rs1196333, XRCC1 G/A rs25487, XRCC5 T/C rs1051677 and TGFB1 C/T rs1800469). In addition, Kaplan-Meier analyses have also highlighted significant association between genotypes and length of patients’ follow-up after radiotherapy. Multivariate logistic regression has further sustained these results suggesting predictive and prognostic roles of SNPs.ConclusionsUnivariate and multivariate analysis suggest that radiation toxicity in radiotherapy patients are associated with certain SNPs, in genes including HDM2 promoter studied for the 1st time. These results support the use of SNPs as genetic predictive markers for clinical radiosensitivity and evoke a prognostic role for length of patients’ follow-up after radiotherapy.