Epstein-Barr virus and its association with Fascin expression in colorectal cancers in the Syrian population: A tissue microarray study.

Colorectal cancer (CRC) is the third most common malignancy in both men and women worldwide. Colorectal carcinogenesis is a complex, multistep process involving environmental and lifestyle features as well as sequential genetic changes in addition to bacterial and viral infections. Viral infection has a proven role in the incidence of approximately 20% of human cancers including gastric malignancies. Accordingly, Epstein-Barr virus (EBV) has been recently shown to be present in human gastric cancers, which could play an important role in the initiation and progression of these cancers. Therefore, this work explores the prevalence of EBV in 102 CRC tissues from the Syrian population using polymerase chain reaction (PCR) and tissue microarray (TMA) analysis. We found that EBV is present in 37 (36.27%) of CRC samples. Additionally, the expression of LMP1 onco-protein of EBV was found to be correlated with Fascin expression/overexpression in the majority of CRC tissue samples, which are intermediate/high grade invasive carcinomas. Our data indicate that EBV is present in CRC and its presence is associated with more aggressive cancer phenotype. Consequently, future investigations are needed to expose the role of EBV in CRC initiation and progression.

Co-prevalence of Epstein-Barr virus and high-risk human papillomaviruses in Syrian women with breast cancer.

ABSTRAT We recently performed 2 studies viewing the presence of Epstein-Barr virus (EBV) and high-risk human papillomaviruses (HPVs) types 16, 18, 31, 33 and 35 in human breast cancer in the Syrian population. Herein, we report that EBV and high-risk HPVs are co-present in breast cancer in Syrian women. Therefore, and based on our previous studies and present data, we reveal that 35 (32%) of 108 cancer samples are positive for both EBV and high-risk HPVs and their co-presence is associated with high grade invasive ductal carcinomas (IDCs) with at least one positive lymph nodes, in comparison with EBV and high-risk HPVs-positive samples, which are low to intermediate grade IDCs, respectively. Future studies are needed to confirm the co-presence and the cooperation effect of these onco-viruses in human breast carcinogenesis and metastasis.

Incidence of Epstein-Barr virus in Syrian women with breast cancer: A tissue microarray study.

Epstein-Barr virus (EBV) has been recently shown to be present in human breast cancer worldwide, which could play an important role in the initiation and progression of this cancer. In this regard, we aimed to explore the prevalence of EBV in 108 breast cancer tissues from Syrian women using polymerase chain reaction (PCR) and tissue microarray (TMA) analysis. We found that EBV is present in 56 (51.85%) of breast cancers samples. Additionally, we report that the expression of LMP1 gene of EBV is associated with a cancer invasive phenotype in the majority of the cancer samples. These data imply that EBV is present in breast cancer worldwide including Syria and its presence is associated with more aggressive cancer phenotype. Thus, future investigations are needed to elucidate the exact role of EBV in breast carcinogenesis and metastasis.

Human papillomaviruses-related cancers. Presence and prevention strategies in the Middle east and north African regions.

Human papillomavirus (HPV) infections are estimated to be the most common sexually transmitted infections worldwide. Meanwhile, it is well established that infection by high-risk HPVs is considered the major cause of cervical cancer since more than 96% of these cancers are positive for high-risk HPVs, especially types 16 and 18. Moreover, during the last 2 decades, numerous studies pointed-out the possible involvement of high-risk HPV in several human carcinomas including head and neck, colorectal and breast cancers. The association between high-risk HPVs and cervical cancer and potentially other human malignancies would necessitate the introduction of vaccines which were generated against the 2 most frequent high-risk HPVs (types 16 and 18) worldwide, including the Middle East (ME) as well as North African countries. The presence of high-risk HPVs in the pathogenesis of human cancers in the ME, which is essential in order to evaluate the importance of vaccination against HPVs, has not been fully investigated yet. In this review, we present an overview of the existing epidemiological evidence regarding the presence of HPV in human cancers in the ME and the potential impact of vaccination against HPV infections and its outcome on human health in this region.

High-Risk HPVs and Human Carcinomas in the Syrian Population.

Human papillomavirus (HPV) infection is the most common sexually transmitted infection; persistent infection with high-risk types of HPV present a major risk factor for the initiation and progression of a variety of human carcinomas including cervical, colorectal, head, and neck (HN) as well as breast carcinomas. A huge number of studies investigated and reported the incidence of high-risk HPVs in these cancers worldwide particularly in the developed countries; therefore, two HPV prophylactic vaccines against the two most frequent high-risk HPV types (16 and 18) have been developed and used worldwide. However, there are very limited studies about the prevalence of HPVs in the developing countries especially in Africa and some states of the Middle East. In this mini review, we outline the presence of high-risk HPVs in human cervical, colorectal, HN as well as breast cancers in the Syrian population, which was recently explored for the first time by a Canadian/Syrian group.

Allele Frequencies of the Epidermal Growth Factor Receptors Polymorphism R521K in Colorectal Cancer Patients and Healthy Subjects Indicate a Risk-Reducing Effect of K521 in Syrian Population.

BACKGROUND: Colorectal cancer contributes heavily to cancer morbidity and mortality worldwide. Numerous therapies are currently in use, including monoclonal antibodies against cellular components involved in tumorigenesis such as epidermal growth factor receptors (EGFRs). Studies showed the polymorphism [R521K] GàA in the EGFR gene to be involved in both colorectal cancer susceptibility and clinical response to therapeutics (e.g., Cetuximab). AIM: We aimed at uncovering allele frequencies of this polymorphism among Syrian colorectal cancer patients and healthy individuals. MATERIALS AND METHODS: Forty-seven patients with colorectal cancer were included in a case-control study along with 48 healthy subjects, all native Syrians. Individuals were genotyped using PCR-Restriction Fragment Length Polymorphism (PCR-RFLP) and results were statistically analyzed to elucidate significant differences between the two groups. RESULTS: Allele frequencies were 40.4% (G/G), 57.4% (G/A) and 2.1% (A/A) in colorectal cancer patients and 41.6% (G/G), 43.7% (G/A) and 14.5% (A/A) in healthy subjects. The A/A genotype was significantly lower in colorectal cancer patients than in the control group. CONCLUSIONS: Homozygosity for the A allele is linked to reducing the risk of developing colorectal cancer in Syrian patients. The lower prevalence of (A/A) locally may predict sub-optimal rates of clinical response to Cetuximab compared with populations with higher frequencies of the A allele. Larger scale investigations are needed for a stronger conclusion.

Does the Syrian population have to wait for the new generation of human papillomaviruses vaccine?

We recently conducted several studies regarding the presence of high-risk HPVs in human cervical, colorectal and breast cancers in the Syrian population. Herein, we report that high-risk HPVs type 16, 18, 33, 45, 51, 52 and 58 are frequently present in colorectal cancer in this population. Therefore and based on previous studies and present data, we conclude that the most frequent high-risk HPV types, in the Syrian population, are 16, 18, 33, 35, 45, 51, 52 and 58. Thus, our data suggest that it will be useful to use the new generation of HPV vaccine to protect the Syrian population from high-risk HPVs and their associated cancers.

P53 gene polymorphisms and breast cancer risk in Arab women.

The association between polymorphisms in the p53 tumor suppressor gene and breast cancer risk has been studied in many human populations with conflicting conclusions. However, similar studies in Arab women are not available, and the status of these polymorphisms in this ethnic population is not known. We investigated the status of four known p53 gene polymorphisms and their possible role in breast cancer risk in Arab women. Genotyping was performed for 288 breast cancer women and 188 controls to determine Pro47Ser, Arg72Pro, Intron 3 Ins16 bp and intron 6 (G > C) polymorphisms. The p53 variant Pro47Ser was detected only in one Kuwaiti breast cancer patient and was not detected in any of the control subjects. Frequency of Arg/Arg at codon 72 was 26.6% in controls and 28.1% in patients, Arg/Pro frequency was 59.6% in controls and 69.4% in patients, the Pro/Pro genotype was 13.8% in controls and 2.4% in patients. We observed that women with Pro/Pro genotype have decreased risk for developing breast cancer (OR=0.166, 95% CI=0.067-0.411, p<0.001). The intron 3 genotypes were A1/A1 (48.9%), A1/A2 (40.6%) and A2/A2 (10.5%) in controls and A1/A1(42.4%), A1/A2 (52.8%) and A2/A2 (4.8%) in cases. The intron 6 genotypes were 92.4% (GG), 7.6% (GC) and 0% (CC) in controls and 96.5% (GG), 3.5% (GC) and 0% (CC) in cases. No statistically significant differences between patients and controls were observed for intron 3 and intron 6 polymorphisms. Our data show that proline homozygosity at p53 codon 72 is associated with decreased breast cancer risk in Arab women.

Water pipe smoking and human oral cancers.

While cigarette smoking is recognized as an important risk factor in human oral cancers, the effect of water pipe smoking (WPS) on these cancers is not known. WPS is very common in the young adult population, especially in the Middle East, and has been associated with several respiratory problems. However, to date, there have been no studies examining the association between WPS and the progression of human oral cancers. Currently, the role of WPS in human oral cancers remains uncertain because of the limited number of investigations. This raises the question of whether WPS plays a significant role in the development of human oral carcinomas. In this paper, we propose the hypothesis that human oral normal epithelial cells are vulnerable to persistent WPS; moreover, WPS could play an important role in the initiation of a neoplastic transformation of human normal oral epithelial cells. Therefore, we believe that an international collaboration of epidemiological and clinical studies as well as cellular and molecular biology investigations is necessary to answer this important question.

Association between human papillomavirus and Epstein-Barr virus infections in human oral carcinogenesis.

Infection by high-risk human papillomaviruses (HPVs) and Epstein-Barr virus (EBV) are very frequent in the adult human population, and have been associated with several human carcinomas, especially oral cancers. However, a small number of studies have examined the association between high-risk HPV and EBV in the progression of human oral cancers. Currently, the role of high-risk HPV and EBV co-infections in human oral cancers, particularly nasopharyngeal carcinomas, remain uncertain because of the limited number of investigations. This raises the question whether high-risk HPV and EBV co-infections play a significant role in the development of human nasopharyngeal carcinomas. In this paper, we propose the hypothesis that human oral normal epithelial cells, especially nasopharyngeal cells, are very susceptible to persistent HPV and EBV co-infections; therefore, high-risk HPV and EBV co-infections play an important role in the initiation of a neoplastic transformation of human oral epithelial cells. We believe that significant studies, using different cells and animal models as well as clinical samples, are necessary to answer these important questions.