Abstract
BackgroundSurfactant 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.MethodsThe 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.ResultsThree 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).ConclusionsGenetic variants of SP‐D were associated with risk of RP development in lung cancer patients receiving thoracic radiotherapy.
Highlights
With the increasing lung cancer patients diagnosed, more and more lung cancer patients receive thoracic radiotherapy as a part of standard treatment regimen.[1]
P were calculated by univariate Cox proportional hazard regression model. 95% CI, 95% confidence interval; HR, hazard ratio; PS, performance status of ECOG score standard; radiation pneumonitis (RP), Radiation Pneumonitis; SCLC, small cell carcinoma; V10 (%), percentage of the lung volume that received more than 10 Gy; V20 (%), percentage of the lung volume that received more than 20 Gy; V30 (%), percentage of the lung volume that received more than 30 Gy; V5 (%), percentage of the lung volume that received more than 5 Gy
Three tagSNPs were significantly associated with grade ≥2 RP and haplotype (T‐A‐C) in Surfactant protein D (SP‐D) was significantly associated with both grade ≥2 RP and grade ≥3 RP in lung cancer patients treated with radiotherapy
Summary
This work was supported by the Key Project of Chengdu Military Region During the 12th Five‐year Plan Period (B14005) fund, the Key Research Fund of Chengdu Military General Hospital (2013YG‐A004) and the Research Personnel Project of Chengdu Military General Hospital (41732536).
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