Table 1 Results of two-sample Mendelian randomization analyses on glucose-lowering drug targets and risks of gastrointestinal cancer

ABCC8 + KCNJ11

Anal Carcinoma

2.749 × 10^− 4 (1.18 × 10^− 6, 0.064)

0.003

4.370 × 10^− 6 (1.700 × 10^− 10, 0.112)

0.017

1.000 × 10^− 4 (0.0001, 0.013)

0.0002

Cardia Cancer

4.217 (0.007, 2.46 × 10³)

0.658

0.518 (0.091, 2.952)

0.459

0.600 (0.112, 3.211)

0.550

Gastric Cancer

0.107 (0.001, 22.430)

0.412

0.884 (0.364, 2.147)

0.786

0.835 (0.348, 2.005)

0.687

Hepatocellular Carcinoma

0.009 (1.01 × 10^− 4, 0.852)

0.042

0.001 (8.782 × 10^− 5, 0.026)

7.058 × 10^− 6

0.003 (2.000 × 10^− 4, 0.028)

< 0.0001

Intrahepatic Cholangiocarcinoma

440.752 (1.751, 1.11 × 10⁵)

0.031

56.759 (6.941, 464.115)

1.651 × 10^− 4

73.520 (10.312, 524.150)

< 0.0001

Pancreatic Cancer

8.440 (1.633, 43.635)

0.010

56.728 (4.720, 681.753)

0.001

15.058 (3.824, 59.295)

0.0001

Rectum Cancer

3.805 (0.871, 16.620)

0.076

0.280 (0.073, 1.068)

0.062

0.911 (0.338, 2.457)

0.855

DPP4

Anal Carcinoma

4.453 × 10^− 6 (2.04 × 10^− 8, 0.001)

7.325 × 10^− 6

0.447 (0.020, 0.910)

0.005

0.123 (0.020, 0.745)

0.023

Cardia Cancer

0.152 (0.004, 6.255)

0.321

5.092 (0.669, 38.723)

0.402

2.275 (0.383, 13.501)

0.366

Gastric Cancer

0.192 (0.003, 13.660)

0.449

1.251 (0.430, 3.645)

0.681

1.120 (0.397, 3.160)

0.830

Hepatocellular Carcinoma

19.221 (1.47 × 10^− 4, 2.51 × 10⁶)

0.623

3.455 (0.312, 382.858)

0.389

3.988 (0.133, 120.054)

0.426

Intrahepatic Cholangiocarcinoma

7.993 × 10³ (51.330, 1.25 × 10⁶)

4.846 × 10^− 4

3.991 (0.839, 18.977)

0.082

7.733 (1.743, 34.310)

0.007

Pancreatic Cancer

0.315 (0.074, 1.334)

0.117

0.455 (0.053, 3.904)

0.472

0.353 (0.106, 1.170)

0.089

Rectum Cancer

2.685 (0.110, 65.590)

0.545

8.268 (0.278, 246.197)

0.148

4.555 (0.445, 46.650)

0.202

ETFDH

Anal Carcinoma

0.004 (2.47 × 10^− 14, 6.53 × 10⁸)

0.675

0.684 (0.025, 190.226)

0.990

0.589 (0.007, 48.429)

0.814

Cardia Cancer

3.149 × 10^− 4 (6.35 × 10^− 11, 1.56 × 10³)

0.305

1.228 (0.129, 11.711)

0.953

1.032 (0.111, 9.616)

0.978

Gastric Cancer

1.578 (3.17 × 10^− 8, 7.86 × 10⁷)

0.96

0.666 (0.022, 20.340)

0.816

0.687 (0.024, 19.720)

0.826

Hepatocellular Carcinoma

3.949 (1.34 × 10^− 9, 1.16 × 10¹⁰)

0.902

4.262 (0.037, 485.767)

0.345

4.248 (0.042, 434.573)

0.540

Intrahepatic Cholangiocarcinoma

0.070 (5.75 × 10^− 11, 8.57 × 10⁷)

0.803

0.490 (0.000, 611.716)

0.845

0.401 (0.001, 341.417)

0.790

Pancreatic Cancer

8.505 (0.025, 2.95 × 10³)

0.473

6.546 (0.142, 302.443)

0.132

7.082 (0.287, 174.724)

0.231

Rectum Cancer

3.248 (0.012, 8.59 × 10²)

0.679

0.083 (0.001, 9.994)

0.309

0.394 (0.010, 14.895)

0.615

GLP1R

Anal Carcinoma

1.044 × 10⁴ (9.548, 1.14 × 10⁷)

0.010

9.431 (0.194, 458.377)

0.150

49.160 (1.648, 1.466 × 10³)

0.025

Cardia Cancer

3.094 × 10² (3.695, 2.59 × 10⁴)

0.011

17.191 (3.092, 95.583)

0.536

25.073 (5.064, 124.149)

< 0.0001

Gastric Cancer

19.724 (0.189, 2.06 × 10³)

0.209

0.553 (0.293, 1.043)

0.067

1.526 (0.065, 35.899)

0.793

Hepatocellular Carcinoma

0.046 (5.91 × 10^− 4, 3.645)

0.168

2.666 (0.205, 34.673)

0.454

0.942 (0.103, 8.597)

0.958

Intrahepatic Cholangiocarcinoma

63.028 (0.261, 1.52 × 10⁴)

0.139

0.975 (0.187, 5.091)

0.976

1.379 (0.283, 6.714)

0.690

Pancreatic Cancer

1.085 (0.274, 4.292)

0.907

7.414 (0.732, 75.066)

0.090

1.792 (0.549, 5.846)

0.334

Rectum Cancer

4.290 (0.795, 23.160)

0.091

1.136 (0.302, 4.273)

0.851

1.886 (0.665, 5.346)

0.233

GPD2

Anal Carcinoma

2.365 × 10³ (1.74 × 10^− 10, 3.22 × 10¹⁶)

0.615

14.585 (0.004, 500.561)

0.380

17.511 (0.057, 5.406 × 10³)

0.328

Cardia Cancer

0.509 (2.28 × 10^− 7, 1.14 × 10⁶)

0.928

4.010 (0.516, 313.133)

0.078

3.648 (0.160, 83.440)

0.418

Gastric Cancer

2.869 × 10³ (1.32 × 10^− 4, 6.25 × 10¹⁰)

0.356

1.267 (0.040, 40.233)

0.893

1.729 (0.058, 51.164)

0.752

Hepatocellular Carcinoma

2.161 (3.09 × 10^− 7, 1.51 × 10⁷)

0.924

0.009 (7.779 × 10^− 8, 1.132 × 10³)

0.434

0.065 (0.0001, 779.411)

0.568

Intrahepatic Cholangiocarcinoma

3.333 × 10⁴ (6.74 × 10^− 5, 1.65 × 10¹³)

0.308

0.002 (7.750 × 10^− 8, 76.031)

0.254

0.078 (0.0001, 766.568)

0.586

Pancreatic Cancer

8.064 (0.024, 2.71 × 10³)

0.482

12.495 (0.003, 4.623 × 10⁴)

0.547

9.334 (0.081, 1.076 × 10³)

0.357

Rectum Cancer

0.004 (1.83 × 10^− 5, 0.728)

0.038

0.062 (0.003, 1.277)

0.086

0.031 (0.002, 0.428)

0.010

INSR

Anal Carcinoma

1.095 × 10³ (0.001, 1.99 × 10⁹)

0.341

0.381 (0.008, 173.995)

0.885

0.889 (0.008, 97.817)

0.961

Cardia Cancer

5.233 × 10³ (0.032, 8.60 × 10⁸)

0.162

9.896 (0.103, 94.798)

0.058

15.804 (0.594, 420.471)

0.099

Gastric Cancer

0.031 (3.35 × 10^− 8, 2.96 × 10⁴)

0.622

2.047 (0.139, 30.057)

0.601

1.756 (0.126, 24.528)

0.676

Hepatocellular Carcinoma

0.050 (4.49 × 10^− 7, 5.49 × 10³)

0.612

0.067 (2.086 × 10^− 4, 21.519)

0.359

0.063 (4.000 × 10^− 4, 11.094)

0.295

Intrahepatic Cholangiocarcinoma

0.001 (4.81 × 10^− 10, 2.41 × 10³)

0.360

0.036 (0.001, 1.513)

0.081

0.029 (0.001, 1.086)

0.056

Pancreatic Cancer

0.397 (0.007, 21.720)

0.651

11.007 (0.023, 5.234 × 10³)

0.446

1.063 (0.037, 30.495)

0.972

Rectum Cancer

0.669 (0.014, 33.000)

0.840

0.428 (0.032, 5.811)

0.524

0.492 (0.056, 4.292)

0.521

PPARG

Anal Carcinoma

42.852 (6.09, 301.523)

1.601 × 10^− 4

3.757 (0.519, 27.180)

0.190

12.909 (3.217, 51.795)

0.0003

Cardia Cancer

1.440 (0.29, 7.151)

0.656

11.018 (5.995, 202.492)

0.109

3.851 (0.525, 28.257)

0.185

Gastric Cancer

0.063 (0.012, 0.339)

0.001

0.758 (0.545, 1.055)

0.101

0.691 (0.500, 0.956)

0.026

Hepatocellular Carcinoma

63.807 (13.260, 306.900)

2.152 × 10^− 7

3.644 (0.150, 88.367)

0.026

36.507 (8.929, 149.259)

< 0.0001

Intrahepatic Cholangiocarcinoma

8.980 (1.241, 64.975)

0.030

5.238 (2.699, 12.193)

0.046

5.609 (2.772, 11.347)

< 0.0001

Pancreatic Cancer

0.290 (0.171, 0.492)

4.549 × 10^− 6

0.010 (0.004, 0.023)

2.371 × 10^− 27

0.110 (0.071, 0.172)

< 0.0001

Rectum Cancer

2.031 (0.616, 6.690)

0.244

1.470 (0.974, 22.190)

0.066

1.803 (0.699, 4.654)

0.223

PRKAB1

Anal Carcinoma

0.035 (4.917 × 10^− 4, 2.539)

0.125

0.608 (7.671 × 10^− 6, 482.378)

0.090

0.059 (0.001, 2.814)

0.151

Cardia Cancer

20.741 (0.854, 503.700)

0.062

3.209 (0.805, 1.279 × 10³)

0.098

9.325 (0.836, 104.023)

0.070

Gastric Cancer

0.285 (0.007, 11.250)

0.503

1.032 (0.551, 1.933)

0.922

0.995 (0.536, 1.847)

0.987

Hepatocellular Carcinoma

0.097 (0.003, 3.010)

0.183

6.206 (0.541, 71.205)

0.143

1.541 (0.211, 11.276)

0.670

Intrahepatic Cholangiocarcinoma

544.800 (7.099, 4.18 × 10⁴)

4.441 × 10^− 3

11.327 (0.369, 477.766)

0.067

54.449 (3.434, 863.226)

0.005

Pancreatic Cancer

0.599 (0.133, 2.703)

0.505

0.157 (0.025, 0.975)

0.069

0.348 (0.109, 1.114)

0.075

Rectum Cancer

2.403 (0.757, 7.626)

0.137

3.529 (0.110, 112.742)

0.333

2.497 (0.835, 7.470)

0.102

SLC5A2

Anal Carcinoma

0.153 (0.004, 6.058)

0.317

0.370 (0.009, 15.078)

0.599

0.237 (0.017, 3.230)

0.280

Cardia Cancer

43.268 (2.771, 675.700)

0.007

11.038 (3.381, 36.036)

6.951 × 10^− 5

13.666 (4.610, 40.515)

< 0.0001

Gastric Cancer

0.652 (0.016, 26.550)

0.821

29.569 (11.585, 551.493)

0.065

6.183 (0.156, 244.359)

0.332

Hepatocellular Carcinoma

100.541 (2.926, 3.455 × 10³)

0.011

22.507 (4.289, 118.097)

0.092

29.465 (6.568, 132.195)

< 0.0001

Intrahepatic Cholangiocarcinoma

46.219 (0.439, 4.868 × 10³)

0.107

1.165 (0.400, 3.393)

0.780

1.401 (0.494, 3.971)

0.527

Pancreatic Cancer

6.650 (2.529, 17.486)

1.227 × 10^− 4

15.351 (2.686, 87.744)

0.002

8.096 (3.476, 18.857)

< 0.0001

Rectum Cancer

1.284 (0.432, 3.814)

0.652

1.109 (0.525, 2.341)

0.786

1.162 (0.628, 2.152)

0.633