分子遺伝医学

Association of hOGG1 Ser326Cys, ITGA2 C807T and TNF-A -308G>A Polymorphisms with the Risk of NPC

Abstract

Eng-Zhuan B, Munn-Sann L, Chong PP, Yoke-Yeow Y, Siew-Ying CL and Rahman HA

Background: Nasopharyngeal carcinoma (NPC) is a rare form of cancer. NPC is the 4th most common cancer in Malaysia and the incidence rate for Malaysian Chinese is exceptionally high compared to other races. NPC is considered as a relatively radiosensitive tumor and patients diagnosed at early stages tend to survive longer compared to those who with advanced disease. Given that early symptoms of NPC are non-specific, and that the nasopharynx is relatively inaccessible, less invasive screening methods such as biomarker screening might be the key to improve NPC survival and management. Methodology: A matched case-control study was conducted to investigate the effect of hOGG1 Ser326Cys, ITGA2 C807T and TNF-α -308G>A polymorphisms on the risk of nasopharyngeal carcinoma and all-cause survival. hOGG1 gene encodes for a DNA glycosylase, a protein that is involved in DNA repair. ITGA2 is the alpha subunit of the transmembrane receptor integrin and is mainly responsible for cell-cell and cell-extracellular matrix interaction. TNF-α is a cytokine that is released by immune cells during inflammation. Restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) was used to process DNA genotyping studies involving all aforementioned gene polymorphisms. Conditional logistic regression was used for the analysis of NPC risk on gene polymorphisms, controlling for cigarette smoking, salted fish and alcohol consumption. Results: Conditional logistic regression showed that NPC cases were more likely to ever consume salted fish during childhood compared to controls (OR=1.80, 95% CI=1.32-2.46, p<0.01). Individuals with previous smoking history were also at higher risk of NPC (OR=1.96, 95% CI=1.37-2.81, p<0.01). No significant difference was found between NPC cases and controls for alcohol consumption. No significant association was observed between hOGG1 Ser326Cys, ITGA2 C807T, TNF-α -308G>A polymorphisms with NPC risk. Conclusion: None of the aforementioned polymorphisms showed significant association in increasing NPC risk individually.