Table 2.

Association of Selected SNPs on 5p15 and 15q25 Loci with Lung Cancer Risk Overall and by Histologic Types and Smoking Status

Marker,aAllele,bLocation,cGene,dMAFe	Study	Overall NCI Data		Adenocarcinoma NCI Data		Squamous Cell Carcinoma NCI Data:		Small Cell Carcinoma NCI Data:
		p Valuef	ORg(95% CI)	p Valuef	ORg(95% CI)	p Valuef	ORg(95% CI)	p Valuef	ORg(95% CI)
SNPs on Chromosome 5p15
rs2736100, (T,G), 1339516, TERT, 0.499/0.466	NCI_Smoking Unadjusted	0.001	1.09 (1.03, 1.15)	3.02 × 10−7	1.23 (1.13,1.33)	0.84	1.01 (0.93, 1.10)	0.93	1.00 (0.90, 1.13)
	NCI_Current smokers	0.41	1.03 (0.96-1.11)	0.001	1.23 (1.09, 1.39)	0.37	0.95 (0.85, 1.06)	0.77	0.98 (0.85, 1.12)
	NCI_Former smokers	0.02	1.11 (1.02, 1.22)	0.01	1.17 (1.03, 1.33)	0.13	1.13 (0.97, 1.31)	0.81	1.03 (0.81, 1.30)
	NCI_Never smokers	0.002	1.34 (1.11, 1.61)	0.01	1.35 (1.07, 1.71)	0.33	0.74 (0.40, 1.35)	0.18	1.95 (0.70, 5.23)
	Meta-analysis Unadjusted	1.60 × 10-10	1.12 (1.08, 1.16)	3.74 × 10-14	1.24 (1.17, 1.31)	0.69	0.99 (0.93, 1.05)	0.48	0.97 (0.89, 1.05)
rs31489, (C,A), 1395714, CLPTM1L, 0.411/0.385	NCI_Smoking Unadjusted	2.80 × 10-4	0.90 (0.86, 0.95)	0.067	0.93 (0.86, 1.00)	8.51 × 10-5	0.84 (0.77, 0.91)	0.089	0.90 (0.80, 1.01)
	NCI_Current smokers	0.008	0.90 (0.83-0.97)	0.21	0.92 (0.82, 1.05)	0.0003	0.81 (0.73, 0.91)	0.22	0.92 (0.80, 1.05)
	NCI_Former smokers	0.33	0.95 (0.87, 1.05)	0.68	0.97 (0.86, 1.11)	0.35	0.93 (0.79, 1.09)	0.11	0.82 (0.64, 1.05)
	NCI_Never smokers	0.37	0.92 (0.77, 1.10)	0.45	0.92 (0.73, 1.15)	0.41	0.77 (0.41, 1.44)	0.76	1.15 (0.47, 2.85)
	Meta-analysis Unadjusted	1.56 × 10−10	0.89 (0.86, 0.92)	0.005	0.92 (0.87, 0.98)	1.39 × 10−5	0.87 (0.81, 0.92)	0.024	0.91 (0.83, 0.99)
rs4635969, (C,T), 1361552, TERT, CLPTM1L, 0.199/0.184	NCI_Smoking Unadjusted	9.80 × 10−5	0.87 (0.82, 0.93)	5.49 × 10−5	0.81 (0.73, 0.90)	0.031	0.88 (0.79, 0.99)	0.055	0.86 (0.74, 1.00)
	NCI_Current smokers	0.08	0.92 (0.83, 1.01)	0.02	0.82 (0.70, 0.96)	0.12	0.89 (0.77, 1.03)	0.20	0.89 (0.74, 1.06)
	NCI_Former smokers	0.001	0.83 (0.74, 0.93)	0.006	0.80 (0.68, 0.94)	0.20	0.88 (0.72, 1.07)	0.11	0.77 (0.56, 1.06)
	NCI_Never smokers	0.27	0.88 (0.69, 1.11)	0.08	0.76 (0.56, 1.04)	0.61	1.21 (0.58, 2.52)	0.73	0.81 (0.23, 2.78)
	Meta-analysis Unadjusted	2.15 × 10−8	0.88 (0.84, 0.92)	6.39 × 10−6	0.83 (0.77, 0.90)	0.005	0.88 (0.80, 0.96)	0.20	0.92 (0.80, 1.05)
SNPs on Chromosome 15q25
rs12914385, (C,T), 76685778, CHRNA3, 0.386/0.452	NCI_Smoking Unadjusted	5.24 × 10−27	1.34 (1.27, 1.42)	3.93 × 10−14	1.36 (1.25, 1.47)	5.23 × 10−12	1.36 (1.24, 1.48)	3.76 × 10−8	1.38 (1.23, 1.55)
	NCI_Current smokers	6.12 × 10−18	1.41 (1.31, 1.53)	2.88 × 10−8	1.42 (1.25, 1.61)	2.12 × 10−8	1.38 (1.23, 1.55)	4.28 × 10−7	1.43 (1.25, 1.65)
	NCI_Former smokers	6.11 × 10−10	1.34 (1.22, 1.47)	5.65 × 10−7	1.38 (1.22, 1.57)	2.92 × 10−5	1.39 (1.19, 1.62)	0.05	1.27 (1.00, 1.61)
	NCI_Never smokers	0.24	1.11 (0.93, 1.34)	0.24	1.15 (0.92, 1.46)	0.84	0.94 (0.50, 1.75)	0.16	2.00 (0.76, 5.27)
	Meta-analysis Unadjusted	2.75 × 10−38	1.30 (1.25, 1.36)	3.32 × 10−18	1.31 (1.23, 1.40)	8.72 × 10−13	1.30 (1.21, 1.40)	2.31 × 10−9	1.37 (1.24, 1.52)
rs1051730, (C,T), 76681394, CHRNA5,CHRNA3, 0.348/0.413	NCI_Smoking Unadjusted	3.63 × 10−25	1.33 (1.26, 1.41)	4.21x10−14	1.36 (1.26, 1.47)	1.93x 10−9	1.31 (1.20, 1.43)	6.70 × 10−8	1.38 (1.23, 1.55)
	NCI_Current smokers	1.30 × 10−17	1.42 (1.31, 1.53)	1.03x10−8	1.44 (1.27, 1.63)	4.7x10−7	1.34 (1.20, 1.50)	2.58 × 10−7	1.45 (1.26, 1.67)
	NCI_Former smokers	3.66 × 10−8	1.30 (1.19, 1.43)	8.05x10-7	1.38 (1.21, 1.57)	0.0005	1.32 (1.13, 1.54)	0.13	1.20 (0.95, 1.54)
	NCI_Never smokers	0.14	1.15 (0.96, 1.38)	0.22	1.16 (0.92, 1.46)	0.71	1.13 (0.60, 2.11)	0.08	2.44 (0.91, 6.51)
	Meta-analysis Unadjusted	1.91 × 10−51	1.31 (1.27, 1.36)	7.10 × 10−19	1.32 (1.24, 1.41)	1.01 × 10−10	1.28 (1.18, 1.37)	3.18 × 10−9	1.37 (1.23, 1.52)
rs8034191, (T,C), 76593078, LOC123688, 0.352/0.414	NCI_Smoking Unadjusted	6.19 × 10−20	1.29 (1.22, 1.36)	1.61 × 10−10	1.30 (1.20, 1.40)	1.10 × 10−7	1.26 (1.16, 1.38)	1.31 × 10−5	1.29 (1.15, 1.45)
	NCI_Current smokers	3.51 × 10−14	1.36 (1.25, 1.47)	4.14 × 10−7	1.38 (1.22, 1.56)	2.49 × 10−5	1.27 (1.14, 1.43)	7.14 × 10−5	1.33 (1.15, 1.53)
	NCI_Former smokers	1.52 × 10−7	1.29 (1.17, 1.41)	1.33 × 10−5	1.33 (1.17, 1.51)	0.0004	1.32 (1.13, 1.54)	0.10	1.22 (0.96, 1.56)
	NCI_Never smokers	0.72	1.03 (0.86, 1.24)	0.77	1.04 (0.82, 1.31)	0.90	1.04 (0.56, 1.94)	0.11	2.21 (0.84, 5.82)
	Meta-analysis Unadjusted	2.18 × 10-46	1.29 (1.25, 1.34)	1.46 × 10−15	1.29 (1.21, 1.37)	3.37 × 10−9	1.25 (1.16, 1.34)	4.49 × 10−7	1.31 (1.18, 1.45)

Bold font indicates genome-wide significant results

Overall NCI Data: 5848 controls (2384 current, 2041 former,1402 never smokers), 5739 cases (3410 current, 1946 former, 362 never smokers). Meta-analysis: 19666 controls, 13300 cases

Adenocarcinoma NCI Data: 5848 controls (2384 current, 2041 former,1402 never smokers), 1730 cases (786 current, 731 former, 203 never smokers). Meta-analysis: 14933 controls, 3333 cases

Squamous Cell Carcinoma NCI Data: 5848 controls (2384 current, 2041 former,1402 never smokers), 1400 cases (953 current, 422 former, 23 never smokers). Meta-analysis: 14933 controls, 2589 cases

Small Cell Carcinoma NCI Data: 5848 controls (2384 current, 2041 former,1402 never smokers), 678 cases (516 current, 152 former, 9 never smokers). Meta-analysis: 13796 controls, 1418 cases

Most notable SNPs from the NCI GWAS and SNPs identified as relevant for lung cancer risk in previous studies are shown. The lung cancer cases in the Overall analyses include adenocarcinomas, squamous cell carcinomas, small cell carcinomas, and other groups of different histologic types or mixed histologies. The Overall meta-analyses include four NCI GWAS studies plus ten additional studies; the meta-analyses in the three major histologic types include four NCI GWAS studies plus four replication studies for the SNPs on chromosome 5p15 and three replication studies for the SNPs on chromosome 15q25. Results for each SNP are shown in this order: Top row (NCI_Smoking Unadjusted), results from the NCI GWAS data adjusted for age in five-year intervals (defined as age-at-diagnosis/interview for case-control study and age at baseline for cohort study), gender, study (EAGLE, PLCO, ATBC, CPS-II) and four principal components for population stratification within studies (two for PLCO, and one each for EAGLE and ATBC). Adjustment for the same variables plus smoking status (current, former, never), cigarettes smoked per day (≤10, 11–20, 21–30, 31–40, 41+), duration in ten-year intervals and number of years since quitting (1–5, 6–10, 11–20, 21–30, 30+) for former smokers showed virtually identical results (data not shown). Second row (NCI_Current smokers), results from the NCI GWAS data restricted to current smoker subjects, adjusted for the same variables of the top row. Third row (NCI_Former smokers), results from the NCI GWAS data restricted to former smoker subjects who quit smoking > 6 months prior to the study, adjusted for the same variables of the top row. Fourth row (NCI_Never smokers), results from the NCI GWAS data restricted to never smoker subjects who smoked < 100 cigarettes in their lifetime, adjusted for the same variables of the top row. Bottom row (Meta-analysis Unadjusted), results from the meta-analysis combining NCI GWAS data and ten additional studies, unadjusted models.

^aNCBI dbSNP identifier.

^bMajor allele, minor allele.

^cChromosome and NCBI Human genome Build 36 location.

^dGene neighborhood within 20 kb upstream and 10 kb downstream of SNP.

^eMinor allele frequency in controls/cases.

^f1d.f. Wald test.

^gOR, per-allele odds ratio; CI, 95% confidence interval.