Genetic variants of SP-D confer susceptibility to radiation pneumonitis in lung cancer patients undergoing thoracic radiation therapy.

Background: Surfactant protein D (SP-D) is an innate immunity molecule in the alveoli. However, the associations between genetic variants of SP-D and radiation pneumonitis (RP) have never been investigated.

Methods: The Linkage disequilibrium of SP-D and tagSNPs were analyzed by using Haploview 4.1. Eight tagSNPs were genotyped among 396 lung cancer patients who received thoracic radiation therapy with follow-up time (median [P25, P75]: 11[6, 18]) using improved multiplex ligation detection reaction (iMLDR). The associations between clinical characteristics, tagSNP alleles, genotypes, haplotypes and onset time of grade ≥2 or ≥3 RP were evaluated by using univariate and multivariate Cox proportional hazard regression model.

Results: Three tagSNPs of SP-D (rs1998374, rs911887 and rs2255326) were significantly associated with grade ≥2 RP in multivariate analysis with multiple testing (Q test). The rs199874 had a protective effect for grade ≥2 RP in the dominant model (Hazard ratio (HR), 0.575; 95% confidence interval (CI), 0.378-0.875). The homozygous mutant genotype for rs911887 had risk effect for grade ≥2 RP (HR, 2.209; 95% CI, 1.251-3.902). The A mutant allele of rs2255326 also showed an elevated risk for grade ≥2 RP (HR, 1.777; 95% CI, 1.283-2.461) and this risk effect was still significant in the recessive genetic model (HR, 3.320; 95% CI, 1.659-6.644) and dominant genetic model (HR, 1.773; 95% CI, 1.166-2.696). Compared to the lung cancer patients bearing the most common haplotype C-G-T, the patients bearing the haplotype T-A-C (rs1998374-rs2255326-rs911887) showed a significant risk of both grade ≥2 RP (HR, 1.885; 95% CI, 1.284-2.765) and grade ≥3 RP (HR, 2.256; 95% CI, 1.248-4.080).

Conclusions: Genetic variants of SP-D were associated with risk of RP development in lung cancer patients receiving thoracic radiotherapy.