Genetic polymorphisms in the vitamin D pathway in relation to lung cancer risk and survival

// Jinyu Kong 1,2,3 , Fangxiu Xu 1 , Jinli Qu 1 , Yu Wang 1 , Ming Gao 1 , Herbert Yu 4 and Biyun Qian 1,3 1 Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Tianjin, China 2 Department of Cancer Epigenetics Laboratory, First Affiliated Hospital of Henan University of Science and Technology, Luoyang, China 3 Hongqiao International Institute of Medicine, Shanghai Tongren Hospital/Faculty of Public Health, Shanghai Jiao Tong University School of Medicine, Shanghai, China 4 Epidemiology Program, University of Hawaii Cancer Center, Honolulu, HI, USA Correspondence: Biyun Qian, email: // Keywords : non-small cell lung cancer, vitamin D pathway, single nucleotide polymorphism, genetic susceptibility, prognosis Received : October 02, 2014 Accepted : December 09, 2014 Published : December 10, 2014 Abstract Studies have suggested that vitamin D may have protective effects against cancer development or tumor progression. To search for additional evidence, we investigated the role of genetic polymorphisms involved in the vitamin D pathway in non-small cell lung cancer (NSCLC). We evaluated common genetic polymorphisms associated with the vitamin D pathway in relation to NSCLC in a case-control study of 603 newly diagnosed NSCLC patients and 661 matched healthy controls. Seven single nucleotide polymorphisms (SNPs) were genotyped, the expression of CYP27B1 and CYP24A1 were measured in 153 tumor samples and their associations with genotypes and patient survival were also analyzed. In the case-control comparison, we found SNP rs3782130 ( CYP27B1 ), rs7041 ( GC ), rs6068816 and rs4809957 ( CYP24A1 ) associated with NSCLC risk. The risk of NSCLC was increased with the number of risk alleles. CYP27B1 and CYP24A1 expression were significantly different between tumor and normal tissues in NSCLC. High CYP27B1 expression was associated with better overall survival, and the expression was different by the rs3782130 genotype. The study suggests that some genetic polymorphisms involved in the vitamin D pathway may associate with NSCLC risk, and one of the polymorphisms (rs3782130) may affect gene expression and patient survival.