| Abstract |
The multi-event nature of carcinogenesis has led to extensive studies focusing on the involvement of several cellular oncogenes, oncosuppressor genes, viral genes and their combined participation in the development of human cancers. Carcinogenesis is a multi-stage process and the exposure to environmental chemicals plays an important role in it. The collaboration of a variety of genetic factors, gene mutations and specific gene polymorphism in esophageal cancer lesions and their interactions and correlation with their host and the environment have also been extensively studied.
Esophageal cancer is the ninth most common malignancy, and represents the sixth most frequent cause of death from cancer worldwide. When the cancer ESCC is diagnosed, the majority of neoplasms are unresectable or with metastases. The high-risk countries include Eastern Turkey, Former Soviet Union, Iraq, Iran, Western and Northern China, Hong-Kong, Japan, termed as the Asian esophageal cancer belt. Also South Africa, Brazil, and France have been reported as high-risk areas. Risk factors for esophageal cancer include cigarette smoking, alcohol abuse, and diet deficient in vitamins and antioxidants. The detection rate of the human papilloma virus (HPV) have an overall incidence of 22%.
The purpose of the present study was to evaluate the incidence of HPV and EBV DNA genomes within esophageal SCC specimens derived from Greek population, in order to further investigate their putative contribution and association with ESCC malignancy. Also to determine the incidence and consequently the possible implication of B-raf, K-ras, and N-ras gene mutations in ESCC development. and the correlation with clinicopathological features of the patients including gender, HPV infection and habits such as tobacco or alcohol use.
For this purpose was used the polymerase chain reaction method (PCR) for the amplifiacation of the target genes, followed by the intermittent restriction digestion (RFLP) for mutation detection of the K-ras, and N-ras codon 12, and BRAF V600E genes.
Our results in virus aetiology of ESCC, indicated that seventeen out of thirty ESCC specimens (56%) were found positive for HPV DNA, by which fifteen (88%) typed as HPV-18 infected, one (5.9%) as HPV-16 and one (5.9%) as type different from the studied 6, 11, 16, 18 and 33 HPV subtypes. Six out of twenty seven normal esophageal specimens (22.2%) were positive for HPV infection, five typed as HPV-18 (83.3%) and one as HPV-16 (16.7%). All samples were negative in EBV genome detection, as assessed by the PCR assay. In conclusion, our findings indicate a statistically significant (p<0.001) overall association between ESCC incidence and HPV infection, mostly related to HPV-18 subtype, in the Greek population
Our results in genome aetiology of ESCC, indicated that Among the genes tested, only the heterozygous K-ras mutation was detected in 5 out of the 30 ESCC specimens (16%), whereas no mutation was found in the normal esophageal tissue (p<0.022). The normal samples were screened negative for N-ras and V600E B-raf mutations. The increased risk of esophageal cancer was correlated with tobacco users (OR=3.5, p<0.023) and alcohol abusers (OR=7.22, p<0.001), accompanied with the high incidence of the k-ras codon 12 mutation (22%, OR=1.77 and 21%, OR=1.52), respectively. A similar positive association was seen in HPV-infected patients (OR=5.66. p<0.003). Our overall findings demonstrate that the mutational activation of the K-ras gene, HPV infection and tobacco or alcohol abuse, can be considered independently or in combination as high risk factors for ESCC development.
Our overall findings demonstrate that the mutational activation of the K-ras gene, HPV infection and tobacco or alcohol abuse, can be considered independently or in combination as high risk factors for ESCC development.
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Ο ρόλος του ιού του θηλώματος του ανθρώπου (HPV) σε ακανθοκυτταρικό καρκίνωμα του οισοφάγου (ESCC)
