OBJECTIVE: To explore the association between DNA damage-related genetic 
variants and lung cancer susceptibility in a Han Chinese population.
METHODS: This case-control study enrolled patients from the Cancer Hospital of 
Jiangsu Province and Jiangsu Province Hospital from 2003 to 2009. Controls were 
randomly selected from individuals who visited the same hospital or a 
community-based health examination program during the same time period. A 5 ml 
venous blood sample was obtained from each participant and epidemiological 
information was collected on a standard questionnaire. Illumina Infinium(®) 
BeadChip was used for genotyping of 35 DNA damage-related single nucleotide 
variations (SNVs), which were identified in our previous study. Multivariate and 
binary logistic regressions were used to calculate the OR and 95%CI for lung 
cancer risk. HaploReg V4.1 and Regulome DB were used to understand functional 
annotation on important SNV.
RESULTS: The distributions of age (61.06±10.15) vs. (61.32±11.07) years; 
t=-0.72, P=0.473) and sex (χ(2)=1.81, P=0.179) were similar between cases and 
controls. However, the case group had a higher frequency of smokers (61.08% vs. 
48.54%; χ(2)=50.04, P<0.001) and heavy smokers (42.28% vs. 24.07%; χ(2)=122.32, 
P<0.001). Among the 34 SNVs that passed quality control, two SNVs were 
significantly associated with lung cancer risk after adjustments for age, sex 
and cumulative smoking dose: rs9267576 C>A (CA genotype/CC genotype, OR=1.56, 
95% CI: 1.01-2.40) and rs3130683 A>G (AG genotype/AA genotype, OR=1.87, 95%CI: 
1.13-3.09). After step-wise logistic regression analysis, only the rs3130683 SNV 
was retained in the model, indicating that the association between rs9267576 and 
lung cancer may be due to the effect of rs3130683. Functional annotation 
indicated that rs3130683 was located in the promoter and enhancer regions, and 
was an expression quantitative trait loci of HLA. The Cancer Genome Atlas 
indicated that expression of HLA-C, DQB1, DRB1 and DRB5 in lung cancer tissue 
was significantly lower than in paired normal tumor-adjacent tissue, with 
down-regulation of the four respective genes in 81.3%, 88.8%, 90.7% and 90.7% of 
lung cancer tissues (P-values were 6.68×10(-15), 2.21×10(-13), 2.20×10(-16), 
2.58×10(-13), respectively).
CONCLUSIONS: The SNV rs3130683 (A>G) was associated with the risk of lung cancer 
in a Han Chinese population. This SNV may affect the risk of lung cancer by 
regulating HLA expression.