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

• Published in: Oncotarget 2015-02, Vol.6 (4), p.2573-2582
• Main Authors: Kong, Jinyu, Xu, Fangxiu, Qu, Jinli, Wang, Yu, Gao, Ming, Yu, Herbert, Qian, Biyun
• Format: Article
• Language: English
• Subjects: 25-Hydroxyvitamin D3 1-alpha-Hydroxylase - genetics; 25-Hydroxyvitamin D3 1-alpha-Hydroxylase - metabolism; Biosynthetic Pathways - genetics; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - metabolism; Case-Control Studies; Clinical Research Paper; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Gene Frequency; Genetic Predisposition to Disease - genetics; Genotype; Humans; Kaplan-Meier Estimate; Lung Neoplasms - genetics; Lung Neoplasms - metabolism; Male; Middle Aged; Multivariate Analysis; Polymorphism, Single Nucleotide; Proportional Hazards Models; Reverse Transcriptase Polymerase Chain Reaction; Risk Assessment - methods; Risk Assessment - statistics & numerical data; Risk Factors; Vitamin D - biosynthesis; Vitamin D3 24-Hydroxylase - genetics; Vitamin D3 24-Hydroxylase - metabolism
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.2951

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.