Runs of homozygosity （ROHs） are a class of important but poorly studied genomic variations and may be in- volved in individual susceptibility to diseases. To better understand ROH and its relationship with lung cancer, we performed a genome-wide ROH analysis of a subset of a previous genome-wide case-control study （1,473 cases and 1,962 controls） in a Han Chinese population. ROHs were classified into two classes, based on lengths, intermedi- ate and long ROils, to evaluate their association with lung cancer risk using existing genome-wide single nucleofide polymorphism （SNP） data. We found that the overall level of intermediate ROHs was significantly associated with a decreased risk of lung cancer （odds ratio = 0.63; 95% confidence interval： 0.51-0.77; P = 4.78 × 10-6 ）, while the long ROHs seemed to be a risk factor of lung cancer. We also identified one ROH region at 14q23A that was con- sistently associated with lung cancer risk in the study. These results indicated that ROHs may be a new class of variation which may be associated with lung cancer risk, and genetic variants at 14q23.1 may be involved in the development of lung cancer.
Apoptosis plays a key role in inhibiting tumor growth, progression and resistance to anti-tumor therapy. We hypothesized that genetic variants in apoptotic genes may affect the prognosis of lung cancer. To test this hypoth- esis, we selected 38 potentially functional single nucleotide polymorphisms （SNPs） from 12 genes （BAX, BCL2, BID, CASP3, CASP6, CASP7, CASPS, CASP9, CASPIO, FAS, FASLG and MCL1） involved in apoptosis to assess their prognostic significance in lung cancer in a Chinese case cohort with 568 non-small cell lung cancer （NSCLC） patients. Thirty-five SNPs passing quality control underwent association analyses, 11 of which were shown to be significantly associated with NSCLC survival （P 〈 0.05）. After Cox stepwise regression analyses, 3 SNPs were independently associated with the outcome of NSCLC （BID rs8190315： P = 0.003; CASP9 rs4645981： P = 0.007 and FAS rs1800682： P = 0.016）. A favorable survival of NSCLC was significantly associated with the genotypes of BID rs8190315 AG/GG （adjusted HR = 0.65, 95% CI： 0.49-0.88）, CASP9 rs4645981 AA （HR = 0.22, 95% CI： 0.07-0.69） and FAS rs1800682 GG （adjusted HR = 0.67, 95% CI： 0.46-0.97）. Time-dependent receptor operation curve （ROC） analysis revealed that the area under curve （AUC） at year 5 was significantly increased from 0.762 to 0.819 after adding the risk score of these 3 SNPs to the clinical risk score. The remaining 32 SNPs were not sig- nificantly associated with NSCLC prognosis after adjustment for these 3 SNPs. These findings indicate that BID rs8190315, CASP9 rs4645981 and FAS rs1800682 polymorphisms in the apoptotic pathway may be involved in the prognosis of NSCLC in the Chinese population.
