خطر ابتلا به سرطان دهان توسط ژنوتیپ های پلی مورفیسم XPC و هاپلوتیپ ها
Abstract
1- Introduction
2- Material and methods
3- Results
4- Discussion
References
Abstract
Chewing and smoking of tobacco have been reported to cause DNA damage in oral mucosa which can be repaired by Xeroderma Pigmentosum Group C (XPC) protein. This study aimed to evaluate the association of XPC gene polymorphisms with the risk of oral diseases including oral pre cancer and cancer. In the present study we genotyped 302 patients with oral diseases and 300 healthy controls for XPC PAT (D > I), C > T and A > C polymorphisms with PCR-RFLP and PCR method. Haplotypes were constituted from different XPC genotypes with SNPstats programme. Our results show that individuals with D/I genotype for XPC D > I polymorphism were significantly protected from developing Oral submucous fibrosis (OSMF) and Leukoplakia (p = .029 and 0.031 and respectively). Risk of oral cancer was also significantly lower with the I/I genotype of the same XPC polymorphism (p = .048). However, once oral cancer is established, individual with I allele were at significantly increased risk for having high stage and metastatic tumor (p = .011 and 0.03 respectively). Carrier of T allele for XPC C > T polymorphism were significantly protected from development of OSMF (p = .004) but did not show any association with the development of other pre oral cancerous lesions or oral cancer. In contrast, CC genotype as well as C allele for XPC A > C polymorphism was significantly associated with increased risk of Lichenplanus (p = .006 and 0.004 respectively). XPC C > T and A > C polymorphisms did not show any association with clinical parameters of oral cancer. Haplotype D/T/A and I/T/A showed protective association with development of oral disease (P-value = .001 and 0.0001 respectively). In conclusion, results from the present study demonstrate association of XPC polymorphisms with oral pre cancer and cancer.
Introduction
Compared to the U.S. oral cancer development is high in India (Kekatpure and Kuriakose, 2010). In India, 20 per 100,000 people are affected by oral cancer which accounts for about 30% of all types of cancers. Invasive oral cancer is usually introduced by the presence of clinically known dysplasia of the oral mucosa or oral pre cancerous lesions. These oral pre cancers include, Lichen Planus, Leukoplakia, and Oral submucous fibrosis (OSMF). An oral pre cancerous lesion is defined as a benign, morphologically altered tissue that has a greater than normal risk of cancer transformation (Warnakulasuriya et al., 2007). Caffeine, tobacco, alcohol are known to be associated with a high number of cases of OSMF which are potentially malignant. Carcinogenic molecules from such substances are known to cause oxidative DNA damage to epithelial cells, and can be repaired by cell's own DNA repair mechanisms (Frosina, 2000; Wood et al., 2001). However, faulty DNA repair systems, primarily occurring due to genetic polymorphisms may play a role in the development of oral pre cancer as well as oral cancer (Scully and Bagan, 2009).