The Association Study Between BIM 2903-bp Deletion Polymorphism And The Risk Of Lung Cancer

Objective:Lung cancer is one of the most common carcinomas. The incidence rate of lung cancer is increasing rapidly recent years because of smoking, air-pollution and other environmental cancer-related issues. Bcl-2 family members play an important role in apoptosis, which is essential in the tumorigenesis of lung cancer. BIM is one of BH3-only factors that belong to Bcl-2 family. The 2903-bp deletion polymorphism located in exon 2 of BIM might lead to alternative splicing of the m RNA of BIM, and further result in the lack of BH3 domain. Bim without BH3 domain might lose its function of pro-apoptosis, and lead to the development of cancer. About one of eight east Asians carry the 2903-bp deletion polymorphism. The present study aims to analyze the potential correlation between the deletion polymorphism of BIM and the risk of lung cancer, and whether the 2903-bp polymorphism could be identified as a biomarker of lung cancer.Methods: Present study enrolled 7183 participants, including 2583 histologically confirmed NSCLC patients, 325 histologically confirmed SCLC patients and 4275 healthy participants that without any cancer. High resolution melting curve(HRM) was utilized for genotyping of BIM 2903-bp deletion. Fisher’s exact test were utilized in the association analysis between the deletion polymorphism and participants’ characteristics. The associations between the deletion polymorphism and NSCLC or SCLC were analyzed with logistic regression model. The logistic regression model was also utilized for association studies between the deletion polymorphism and treatment response or toxicities of chemotherapy in NSCLC patients. The cox regression model was utilized for the association study between the deletion polymorphism and overall survival in SCLC patients.Results:In present study, no significant association between BIM2903-bp deletion polymorphism and risk of NSCL was observed neither in combined cohort nor sub-groups. However, carriers of 2903-bp deletion polymorphism had lower risk of thrombocytopenia after chemotherapy(P=0.048).In addition, SCLC patients showed a significant enrichment of 2903-bp deletion polymorphism(P=0.026) in combined cohort, together with smoke, male and elderly sub-groups. Nevertheless, no association was observed between the 2903-bp deletion polymorphism and OS in SCLC patients.Conclusion: No evidence of association between the deletion polymorphism of BIM and the risk of NSCLC was observed in present study. The carriers of 2903-bp deletion polymorphism had higher risk of SCLC, but showed no difference in the prognosis of SCLC.