Association Between Genetic Variations In Surfactant Protein D and Emphysema, Interstitial Pneumonia, and Lung Cancer in a Japanese Population

Figures & data

Table 1.  Genotypes of SFTPD in the subjects with IP, emphysema, and lung cancer

	Subjects with lung cancer (n = 140)	Subjects without lung cancer (n = 1202)	p-value
Age (mean [SD])	79.6 (7.6)	80.4 (9.0)	0.274
Gender
Male	88 (62.9%)	627 (52.2%)	0.016
Female	52 (37.1%)	575 (47.8%)
Smoking status
Ex + current	108 (78.8%)	531 (48.0%)	<0.0001
None	29 (21.2%)	575 (52.0%)
Pack-years (mean [SD])	60.1 (38.6)	48.2 (34.9)	0.003
Emphysema	31 (22.1%)	129 (10.7%)	<0.0001
IP	11 (7.9%)	82 (6.8%)	0.648
IPF/UIP	5 (3.6%)	47 (3.9%)	0.433
AIP/DAD	1 (0.7)	18 (1.5%)	0.458
Collagen Disease-associated	0	5 (0.4%)	0.445
Drug-induced	0	1 (0.1%)	0.733
Organizing pneumonia	0	17 (1.1%)	0.157
Unclassified	2 (1.4%)	12 (1.0%)
Lung cancer
Squamous cell carcinoma	61 (43.6%)
Adenocarcinoma	41 (29.3%)
Adeno-squamous cell carcinoma	7 (5.0%)
Small-cell carcinoma	28 (20.0%)
Large-cell carcinoma	4 (2.9%)
Carcinoid	5 (3.6%)

IPF, idiopathic pulmonary fibrosis; UIP, usual interstitial pneumonia; AIP, acute interstitial pneumonia; DAD, diffuse alveolar damage.

Figure 1.  Association study for rs721917. (A) Emphysema with the additive model. (B) IP with the recessive model. (C) Lung cancer with the dominant, recessive, and additive models. Odds ratios are shown for models in which significant associations were observed.

Table 2.  Associations of SFTPD with emphysema, IP, and lung cancer

	rs721917		rs10887199
	p-value	Adjusted odds ratio (95% CI)	p-value
Emphysema
Dominant	0.148		0.209
Recessive	0.118		0.127
Additive	0.066		0.093
Interstitial pneumonia
Dominant	0.873		0.666
Recessive	0.025	1.98 (1.10–3.41)	0.181
Additive	0.282		0.664
Lung cancer
Dominant	0.01	0.86 (0.34–0.91)	0.825
Recessive	0.044	0.40 (0.18–0.81)	0.885
Additive	0.004	0.62 (0.45–0.85)	0.819

Table 3.  Associations of the haplotype at the rs721917/rs10887199 region with emphysema, interstitial pneumonia, and lung cancer

Haplotype (rs721917/rs10887199)	Haplotype frequency		IP	Emphysema	Lung cancer
		Global p-value	0.12	0.08	0.01
C/C	0.38	beta (SE)	−0.09 (0.36)	0.74 (0.3167)	0.18 (0.30)
		p-value	0.81	0.02	0.56
T/T	0.37	beta (SE)	−0.07 (0.37)	−0.29 (0.34)	−0.88 (0.34)
		p-value	0.85	0.39	0.006
C/T	0.22	beta (SE)	−0.17 (0.42)	−0.44 (0.38)	0.91 (0.31)
		p-value	0.68169	0.24	0.009
T/C	0.04	beta (SE)	1.63 (0.67)	−1.20 (0.93)	−0.92 (0.93)
		p-value	0.02	0.20	0.32

Significant correlations are shown in bold. SE, standard error.

Table 4.  Mediation effect

	Estimate	SE	p-value
Model
Initial factor: SNP rs721917 genotype Mediator: Emphysema Outcome: Lung cancer
Effect
Total effect: SNP on lung cancer	0.14	0.06	0.006
Effect 1: SNP on emphysema	0.09	0.05	0.07
Effect 2 (with given SNP): Emphysema on lung cancer	0.04	0.02	0.04
Mediation effect: SNP on lung cancer through emphysema	0.004	n.a.	0.17
Model
Initial factor: SNP rs721917 genotype Mediator: IP Outcome: Lung cancer
Effect
Total effect: SNP on lung cancer	−0.64	0.32	0.04
Effect 1: SNP on IP	0.59	0.26	0.03
Effect 2 (with given SNP): IP on lung cancer	0.04	0.17	0.83
Mediation effect: SNP on lung cancer through IP	0.02	n.a.	0.83

Table

SNP (Genotype)	Number of subjects for each genotype
	Emphysema	IP	Lung cancer	Whole population
rs721917 (CC/CT/TT)	66/78/17	34/40/21	64/65/13	455/709/205
rs10887199 (TT/TC/CC)	51/78/33	35/39/22	51/70/28	477/670/237