Supplementary Table 1. Associations of 7 excluded SNPs with the survival of early-stage NSCLC patients in the GWAS scan

CHR / Excluded SNPs / Tagging SNPs / r2 values / GWAS scan
HR (95% CI) a / P a
4 / rs898131 / rs17305086 / 0.883 / 2.57(1.70-3.90) / 4.65´10-5
4 / rs10016002 / rs10023113 / 0.915 / 2.38(1.59-3.56) / 8.45´10-5
4 / rs787361 / rs12506221 / 1 / 1.97(1.40-2.76) / 8.36´10-5
5 / rs16878496 / rs13361589 / 0.92 / 3.52(2.13-5.83) / 9.35´10-6
5 / rs7703816 / rs13361589 / 0.92 / 3.34(2.01-5.55) / 2.54´10-5
5 / rs16902206 / rs6883744 / 0.966 / 1.91(1.38-2.63) / 9.72´10-5
5 / rs16876651 / rs6883744 / 0.966 / 1.91(1.38-2.62) / 9.87´10-5

a Results of the additive model with adjustment for age, gender, histology, stage, smoking status and principal-component.

NSCLC, non-small-cell lung cancer; GWAS, genome-wide association study; HR, hazard ratio; CI, confidence intervals.


Supplementary Table 2. Patients’ characteristics and clinical features

Characteristics / GWAS scan (N=354) / Replication cohort (N=327) / Combined cohort (N=681)
Death / 83(23.4%) / 35(10.7%) / 118(17.3%)
MST (months) / 59.27 / 73.61 a / 68.03
Age, yr (mean ± SD) / 61.62±9.91 / 63.16±9.61 / 62.36±9.79
Gender
Male / 256(72.3) / 207(63.3) / 463(68.0)
Female / 98(27.7) / 120(36.7) / 218(32.0)
Smoking status
Never / 136(38.4) / 162(49.5) / 298(43.8)
Ever / 218(61.6) / 165(50.5) / 383(56.2)
Histology
Squamous cell / 119(33.6) / 107(32.7) / 226(33.2)
Adenocarcinoma / 235(66.4) / 220(67.3) / 455(66.8)
Stage
I / 240(67.8) / 215(65.7) / 455(66.8)
II / 114(32.2) / 112(34.3) / 226(33.2)
Adjuvant chemotherapy b
No / 332(93.8) / 291(89.0) / 623(91.5)
Yes / 22(6.2) / 13(4.0) / 35(5.1)

a Mean survival time was provided when MST could not be calculated.

b Adjuvant chemotherapy information were unavailable in 23 patients in the replication cohort.

GWAS, genome-wide association study; MST, median survival time.


Supplementary Table 3. Stratification analyses on CAMK2D rs10023113 and early-stage NSCLC patients’ survival by selected variables

Variable / rs10023113(Patients/Deaths) / Pa / Pb
AA / GA / GG / HR (95% CI)a
Age
£63 / 250/34 / 92/26 / 5/0 / 1.82(1.17-2.84) / 8.45´10-3 / 0.079
>63 / 247/31 / 80/25 / 4/2 / 3.27(2.02-5.29) / 1.47´10-6
Gender
Male / 334/53 / 121/41 / 7/2 / 2.35(1.63-3.36) / 3.70´10-6 / 0.913
Female / 165/12 / 51/10 / 2/0 / 2.46(1.18-5.12) / 1.58´10-2
Smoking
Never / 220/21 / 74/17 / 4/1 / 2.04(1.21-3.42) / 7.44´10-3 / 0.641
Ever / 279/44 / 98/34 / 5/1 / 2.39(1.58-3.62) / 3.85´10-5
Histology
Adenocarcinoma / 327/44 / 121/37 / 6/0 / 1.96(1.34-2.87) / 5.87´10-4 / 0.071
Squamous cell / 172/21 / 51/14 / 3/2 / 3.78(2.07-6.90) / 1.46´10-5
Stage
I / 339/41 / 111/26 / 5/1 / 2.02(1.29-3.19) / 2.36´10-3 / 0.571
II / 160/24 / 61/25 / 4/1 / 2.43(1.55-3.82) / 1.17´10-4

a Adjusted for age, gender, smoking status, histology, and stage except for the stratification factor.

b Heterogeneity test for differences between subgroups.

NSCLC, non-small-cell lung cancer.


Supplementary Table 4. Stepwise Cox regression analysis on NSCLC patients’ survival

Variables / βa / SEb / HR / 95% CI / P
rs10023113 (additive model) / 0.8584 / 0.1611 / 2.36 / 1.72-3.24 / 9.85´10-8
Stage (II vs I) / 0.5068 / 0.1877 / 1.66 / 1.15-2.40 / 6.94´10-3
Age / 0.0190 / 0.0095 / 1.02 / 1.00-1.04 / 4.55´10-2

a β is the estimated parameter of the regression model.

b SE is the standard error of the regression model.

NSCLC, non-small-cell lung cancer; HR, hazard ratio; CI, confidence intervals.

Supplementary FIG.1 Regional plots of rs10023113 in GWA scan. Results (−log10 P) are shown in the region flanking 500 kb on either side of the marker SNPs. The marker SNPs were shown in purple diamond and the R2 values of the rest of the SNPs are indicated by different colors.