Supplemetary TABLE 1 Description of SNPs in LKB1-AMPK-mTOR signaling pathway associated with colorectal cancer

SNP / Allele / Gene / CR (%) / MAF / HWE-p
1 / rs1057079 / AG / mTOR / 100.0 / 0.179 / 0.055
2 / rs1104897 / GA / mTOR / 99.0 / 0.463 / 0.011
3 / rs461404 / TC / PIK3CA / 99.0 / 0.237 / 0.410
4 / rs532678 / CT / PRKAA1 / 96.9 / 0.481 / 0.397
5 / rs6464156 / AG / PRKAA1 / 96.2 / 0.086 / 0.820
6 / rs741765 / AG / PRKAA1 / 97.4 / 0.467 / 0.317
7 / rs7784818 / GA / PRKAG2 / 97.5 / 0.234 / 0.432
8 / rs9648723 / AC / PRKAG2 / 95.5 / 0.145 / 0.052
9 / rs10053664 / TC / PRKAG2 / 95.9 / 0.221 / 0.979
10 / rs2024627 / CT / PRKAG2 / 96.0 / 0.116 / 0.074
11 / rs2727527 / AC / PRKAG2 / 95.9 / 0.474 / 0.824
12 / rs3805490 / AT / PRKAG2 / 96.0 / 0.221 / 0.987
13 / rs7651265 / AG / PRKAG2 / 95.6 / 0.068 / 0.821
14 / rs9632641 / AC / PRKAG2 / 96.1 / 0.077 / 0.428
15 / rs9648724 / GA / PRKAG2 / 96.0 / 0.220 / 0.541
16 / rs11243940 / AG / STK11 / 98.4 / 0.130 / 0.354
17 / rs4725431 / TC / TSC1 / 97.5 / 0.216 / 0.005
18 / rs4128396 / AC / TSC1 / 99.1 / 0.105 / 0.183

CR SNP call rate, MAF minor allele frequency, HWE Hardy-Weinberg equilibrium

1

Supplementary TABLE 2 Genotype frequencies

Gene / Alias / Chromosome / SNP / CR (%) / MAF / HWE-p
STK11 / LKB1 / 19p13.3 / rs741765 / 97.4 / 0.467 / 0.317
AA / 207 / (26.8%)
AG / 388 / (50.2%)
GG / 157 / (20.3%)
PRKAA1 / AMPK / 5p12 / rs461404 / 99.0 / 0.237 / 0.410
TT / 449 / (58.1%)
TC / 268 / (34.7%)
CC / 47 / (6.1%)
TSC1 / LAM / 9q34 / rs13295634 / 99.5 / 0.423 / 0.669
TT / 259 / (33.5%)
TG / 369 / (47.8%)
GG / 140 / (18.1%)

CR SNP call rate, MAF minor allele frequency, HWE Hardy-Weinberg equilibrium, STK11 serine/threonine kinase 11, LKB1 liver kinase B 1, PRKAA1 phosphorylates the adenosine monophosphate-dependent kinase, AMPK adenosine monophosphate-activated protein kinase, TSC1 tuberous sclerosis 1, LAMLymphangioleiomyomatosis

Supplementary TABLE 3 Multivariate Cox analysis according to the combination of 2 risk genotypes

Combination of 2 risk genotypes / N (%) / DFS / OS
HR / 95% CI / p valuea / HR / 95% CI / p valuea
STK11 rs741765 GG / PRKAA rs461404 TT / 25 (8.0) / 1 / 0.283 / 1 / 0.156
PRKAA rs461404 TT / TSC1 rs13295634 TG+GG / 243 (77.9) / 1.876 / 0.672-5.234 / 0.230 / 2.647 / 0.743-9.428 / 0.133
STK11 rs741765 GG / TSC1 rs13295634 TG+GG / 44 (14.1) / 2.073 / 0.837-5.135 / 0.115 / 3.066 / 0.963-9.764 / 0.058

aP values correspond to multivariate Cox model adjusted for age, CEA level, and pathologic stage.

Supplementary FIGURE1Additive effect of the genotypes in STK11, PRKAA1, and TSC1 associated with poor prognosis for patients with colorectal.

Supplementary FIGURE 2 Survival curves according to the combination of two genotypes.

(A)Disease-free survival (B) Overall survival

1