HPV prevalence and genetic predisposition to cervical cancer in Saudi Arabia

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

Combining CDKN1A gene expression and genome-wide SNPs in a twin cohort to gain insight into the heritability of individual radiosensitivity

Individual variability in response to radiation exposure is recognised and has often been reported as important in treatment planning. Despite many efforts to identify biomarkers allowing the identification of radiation sensitive patients, it is not yet possible to distinguish them with certainty before the beginning of the radiotherapy treatment. A comprehensive analysis of genome-wide single-nucleotide polymorphisms (SNPs) and a transcriptional response to ionising radiation exposure in twins have the potential to identify such an individual. In the present work, we investigated SNP profile and CDKN1A gene expression in blood T lymphocytes from 130 healthy Caucasians with a complex level of individual kinship (unrelated, mono- or dizygotic twins). It was found that genetic variation accounts for 66% (95% CI 37-82%) of CDKN1A transcriptional response to radiation exposure. We developed a novel integrative multi-kinship strategy allowing investigating the role of genome-wide polymorphisms in transcriptomic radiation response, and it revealed that rs205543 (ETV6 gene), rs2287505 and rs1263612 (KLF7 gene) are significantly associated with CDKN1A expression level. The functional analysis revealed that rs6974232 (RPA3 gene), involved in mismatch repair (p value = 9.68e-04) as well as in RNA repair (p value = 1.4e-03) might have an important role in that process. Two missense polymorphisms with possible deleterious effect in humans were identified: rs1133833 (AKIP1 gene) and rs17362588 (CCDC141 gene). In summary, the data presented here support the validity of this novel integrative data analysis strategy to provide insights into the identification of SNPs potentially influencing radiation sensitivity. Further investigations in radiation response research at the genomic level should be therefore continued to confirm these findings.Peer reviewe

Retraction Note: SNPs in genes implicated in radiation response are associated with radiotoxicity and evoke roles as predictive and prognostic biomarkers

The authors are retracting this article [1] because the data have already been published in [2] making this a redundant publication. Ghazi Alsbeih, Najla Al-Harbi, Khaled Al-Hadyan, Mohamed Shoukri and Nasser Al-Rajhi agree with this retraction. Medhat El-Sebaie did not respond to our correspondence

Size and time-dependent induction of proinflammatory cytokines expression in brains of mice treated with gold nanoparticles

Gold nanoparticles (GNPs) are among the ideal nano-sized materials for medical applications such as imaging and drug delivery. Considering the significance of recent reports on acute phase induction of inflammatory mediators by GNPs, we studied the effect of GNPs on proinflammatory cytokines gene expression in mouse brain. Group 1 served as control whereas groups 2–4 were given only one intraperitoneal dose of 5, 20 and 50 nm GNPs, respectively and sacrificed after 24 h. The animals in groups 5–7 also received the same treatment but sacrificed after 7 days. Groups 8–10 received two injections of GNPs (5, 20 and 50 nm, respectively), first at the beginning of study and second on day 6, and sacrificed on day 7. Total RNA was extracted from the cerebral tissue and analyzed for the gene expressions of IL-1β, IL-6 and TNF-α. A single injection of 5 nm diameter GNPs significantly increased the mRNA expression of IL-1β and IL-6 in mouse brain on day 7, which was not augmented by the second dose of the same GNPs. Larger size GNPs (20 nm and 50 nm) did not cause any significant change in the expression of proinflammatory cytokines in mouse brain. In conclusion, systemic administration of small sized GNPs (5 nm) induced a proinflammatory cascade in mouse brain indicating a crucial role of GNPs size on immune response. It is important to use the right sized GNPs in order to avoid an acute phase inflammatory response that could be cytotoxic or interfere with the bioavailability of nanomaterials. Keywords: Gold nanoparticles, Proinflammatory cytokines, Brain, Inflammation, Mic

Effect of Air-Frying on the Bioactive Properties of Eggplant (Solanum melongena L.)

The eggplant is an important vegetable that is used all over the world and it contains valuable bioactive properties. Cooking methods affect the nutritional value as well as the functional characteristics of vegetables. This study investigated the effect of air-frying at different temperatures and the extraction solvents on the bioactive properties of eggplant. The eggplant air-fried for 25 min and extracted with 50% ethanol exhibited the highest total flavonoid content (35.10 mg catechin equivalent per gram dry weight), while its total polyphenol content was found as 87.81 mg gallic acid equivalent per gram dry weight. The uncooked sample exhibited the lowest DPPH scavenging (IC50: 422.12 mg/mL reducing power: 0.914), while the highest DPPH scavenging activity (IC50: 2.87 mg/mL; reducing power: 0.936) was recorded for the sample air-fried for 25 min and extracted with 50% ethanol. The highest amount of tannic acid was found in medium-cooked eggplant, while chlorogenic acid was the highest in the high-cooked sample. These results might be helpful for functional food processors