(A) Oral and pharyngeal cancer on non-Hodgkin lymphoma; (B) oral and pharyngeal cancer on myeloma; (C) esophageal cancer on myeloma; (D) colorectal cancer on liver cancer; (E) pancreatic cancer on …
(A) Oral and pharyngeal cancer on non-Hodgkin lymphoma; (B) oral and pharyngeal cancer on myeloma; (C) esophageal cancer on myeloma; (D) colorectal cancer on liver cancer; (E) pancreatic cancer on …
(A) Oral and pharyngeal cancer on non-Hodgkin lymphoma; (B) oral and pharyngeal cancer on myeloma; (C) esophageal cancer on myeloma; (D) colorectal cancer on liver cancer; (E) pancreatic cancer on …
(A) Oral and pharyngeal cancer on non-Hodgkin lymphoma; (B) oral and pharyngeal cancer on myeloma; (C) esophageal cancer on myeloma; (D) colorectal cancer on liver cancer; (E) pancreatic cancer on …
The standardized incidence observed/expected (O/E) ratios and the corresponding 95% confidence intervals were derived using the “MP-SIR” session of SEER*stat (version 8.3.8).
Cancer type | GWAS Source | PMID | Number of SNPs* | Cases | Total population | Variance explained, R2, % | F-statistics |
---|---|---|---|---|---|---|---|
Oral and pharynx | GCST003857 | 27749845 | 7 | 6034 | 12,619 | 2.22 | 283.68 |
Larynx | GCST010285 | 32276964 | 1† | 394 | 4887 | 0.28 | 13.72 |
Esophagus | GCST003740 | 27527254 | 5 | 10,279 | 27,438 | 0.72 | 198.94 |
Stomach | GCST002990 | 26098866 | 1† | 2043 | 202,533 | 0.02 | 34.44 |
Colon and rectum | GCST003017 | 26151821 | 8 | 18,299 | 37,955 | 0.89 | 340.75 |
Pancreas | GCST005434 | 29422604 | 14 | 9040 | 21,536 | 4.28 | 962.28 |
Melanoma | GCST004142 | 28212542 | 17 | 6628 | 293,193 | 0.29 | 852.68 |
Lung | GCST004748 | 28604730 | 7 | 29,266 | 85,716 | 0.55 | 474.00 |
Male Breast | GCST011526 | 32785646 | 2† | 2190 | 6836 | 1.27 | 87.91 |
Female Breast | GCST004988 | 29059683 | 104 | 122,977 | 228,951 | 4.95 | 11917.81 |
Cervix uteri | GCST004833 | 28806749 | 1† | 2866 | 9347 | 0.45 | 42.24 |
Ovary | GCST002748 | 25581431 | 9 | 18,530 | 69,745 | 1.16 | 818.42 |
Prostate | GCST006085 | 29892016 | 71 | 79,148 | 140,254 | 5.47 | 8111.66 |
Bladder | GCST002240 | 24163127 | 7 | 2305 | 6206 | 8.46 | 572.81 |
Kidney | GCST004710 | 28598434 | 8 | 10,784 | 31,190 | 1.11 | 349.99 |
Thyroid | GCST004144 | 28195142 | 6 | 3001 | 290,551 | 0.10 | 290.83 |
Myeloma | GCST004483 | 27363682 | 13 | 9866 | 249,054 | 0.31 | 774.24 |
Note: See Supplementary file 2a: the list of SNPs included in the final calculation for each phenotype.
No study found in European: bone and joint, brain, liver, small intestine, gallbladder, renal pelvis and ureter.
Heterogeneity: lymphoma, leukemia.
Too few SNPs: larynx, stomach, male breast cancer.
Number of SNPs included in the final calculation of PRS in our study; not necessarily the total number of SNPs from the source due to the filtering steps discussed in the main text and germline data availability.
MR would be performed based on at least 4 SNPs.
Cancer type(first primary cancer) | Cancer type (second primary cancer) | ||
---|---|---|---|
Positive Causality | Negative Causality | No Causality(statistical power ≥0.80) | |
Oral and pharynx | Non-hodgkin lymphoma | - | Female breast, Prostate |
Esophagus | - | - | - |
Colon and rectum | - | - | - |
Pancreas | Small intestin | - | Melanoma |
Melanoma | Female breast | - | Colon and Rectum |
Lung | - | Female Breast | - |
Female Breast | - | - | - |
Ovary | Soft tissue | - | - |
Prostate | - | Colon and Rectum | Non-Hodgkin lymphoma |
Bladder | - | - | Female breast, Non-hodgkin lymphoma |
Kidney | Lung and Bronchus, Melanoma, Non-hodgkin lymphoma, Myeloma | - | - |
Thyroid | - | - | - |
Myeloma | - | Lung and Bronchus | - |
See Supplementary file 2c for unconcordant causality result; Supplementary file 2d-p for the details of Mendelian randomization results (IVW and MR-Egger).
Exp-out | Radial IVW | Radial MR-Egger | CAUSE | |||
---|---|---|---|---|---|---|
OR (95% CI) | p | OR (95% CI) | p | OR (95% CI) | p | |
Oropharynx-NHL | 1.21 (1.13–1.30) | 6.00×10–3 | 1.21 (1.13–1.30) | 0.52 | 1.17 (1.05–1.31) | 8.90×10–3 |
Pancreas-Intestin | 1.05 (0.83–1.32) | 0.69 | 2.39 (0.91–6.31) | 0.10 | 1.03 (0.79–1.35) | 1.00 |
Melanoma-Breast | 1.08 (1.00–1.15) | 0.06 | 1.05 (0.84–1.32) | 0.69 | 1.04 (0.95–1.16) | 0.75 |
Lung-Breast | 0.86 (0.79–0.93) | 9.76×10–3 | 0.77 (0.54–1.08) | 0.19 | 0.89 (0.76–1.04) | 0.23 |
Ovary-Soft | 1.39 (1.22–1.58) | 1.07×10–3 | 1.3 (0.74–2.29) | 0.39 | 1.36 (1.16–1.58) | 0.01 |
Prostate-CRC | 1.00 (0.95–1.04) | 0.94 | 0.88 (0.80–0.98) | 0.02 | 0.99 (0.93–1.04) | 0.99 |
Kidney-Lung | 1.17 (1.08–1.27) | 6.60×10–3 | 0.94 (0.62–1.43) | 0.78 | 1.16 (1.02–1.31) | 0.05 |
Kidney-Melanoma | 1.33 (1.02–1.73) | 0.04 | 0.56 (0.18–1.80) | 0.37 | 1.25 (0.96–1.73) | 0.51 |
Kidney-NHL | 1.25 (1.11–1.40) | 7.87×10–3 | 1.33 (0.72–2.46) | 0.39 | 1.20 (0.99–1.43) | 0.09 |
Kidney-Myeloma | 1.72 (1.21–2.45) | 0.02 | 0.43 (0.11–1.77) | 0.29 | 1.49 (1.04–2.34) | 0.02 |
Myeloma-Lung | 0.92 (0.86–0.98) | 0.02 | 1.09 (0.79–1.51) | 0.61 | 0.93 (0.86–1.00) | 0.21 |
IVW, Inverse variance weighted; CAUSE, Causal Analysis Using Summary Effect estimates; OR, odds ratio; CI, confidence interval; exp, exposure; out, outcome; NHL, non-Hodgkin lymphoma; CRC, colorectal cancer.
Standard incidence ratio analysis of different types of cancers in patients with malignancies in SEER database.
Mendelian randomization results of FPCs and SPCs in UK Biobank database.