APOB Genotypes and CDH13 Haplotypes in the Cholesterol-Related Pathway Genes Predict Non-Small Cell Lung Cancer Survival.

BACKGROUND: Several oncogenic signals are involved in the synthesis, metabolism, transportation, and modulation of cholesterol. However, the roles of genetic variants of the cholesterol pathway genes in cancer survival remain unclear. METHODS: We investigated associations between 26,781 common SNPs in 209 genes of the cholesterol pathway and non-small cell lung cancer (NSCLC) survival by utilizing genotyping data from two published genome-wide association studies. We used multivariate Cox proportional hazards regression and expression quantitative trait loci analyses to identify survival-associated SNPs and their correlations with the corresponding mRNA expression, respectively. We also used the Kaplan-Meier survival analysis and bioinformatics functional prediction to further evaluate the identified independent SNPs. RESULTS: We found five independent SNPs (APOB rs1801701C>T; CDH13 rs35859010 C>T, rs1833970 T>A, rs254315 T>C, and rs425904 T>C) to be significantly associated with NSCLC survival in both discovery and replication datasets. When the unfavorable genotype (APOB rs1801701CC) and haplotypes (CDH13 rs35859010-rs1833970-rs254315-rs425904 C-A-T-C and T-T-T-T) were combined into a genetic score as the number of unfavorable genotypes/haplotypes (NUGH) in the multivariate analysis, an increased NUGH was associated with worse survival (P trend < 0.0001). In addition, both APOB rs1801701T

Duke Scholars

Author Sheng Luo Biostatistics & Bioinformatics, Division of Biostatistics

Author Jeffrey Melson Clarke Medicine, Medical Oncology

Author Carolyn Glass Pathology

Author Qingyi Wei Population Health Sciences