Pharmacoepidemiological Research on N-Nitrosodimethylamine-Contaminated Ranitidine Use and Long-Term Cancer Risk: A Population-Based Longitudinal Cohort Study
Abstract
:Simple Summary
Abstract
1. Introduction
2. Materials and Methods
2.1. Data Source
2.2. Study Design and Study Participants
2.3. Potential Confounders
2.4. Covariate Assessment
2.5. Main Outcome Measurements
2.6. Exposure Definition and Follow-Up
2.7. Statistical Analysis
3. Results
3.1. Ranitidine Duration Effect on Cancer Development
3.2. Comparison between Ranitidine and Famotidine for the Association with Patient Outcomes
3.3. Comparison between Ranitidine and PPIs for Their Association with Liver Cancer
4. Discussion
5. Conclusions
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
References
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Characteristics | Untreated n = 55,110 | % | Ranitidine n = 55,110 | % | p-Value | |
---|---|---|---|---|---|---|
Sex | Female | 28,794 | 52.2% | 28,794 | 52.2% | 1.000 |
male | 26,316 | 47.8% | 26,316 | 47.8% | ||
Age (mean ± SD) | 66.8 ± 14.1 | 66.8 ± 14.1 | 1.000 | |||
CCI | 0–1 | 12,444 | 22.6% | 12,444 | 22.6% | 1.000 |
2–3 | 16,205 | 29.4% | 16,205 | 29.4% | ||
4–5 | 12,799 | 23.2% | 12,799 | 23.2% | ||
>5 | 13,662 | 24.8% | 13,662 | 24.8% | ||
HCD | No | 22,204 | 40.3% | 22,204 | 40.3% | 1.000 |
Yes | 32,906 | 59.7% | 32,906 | 59.7% | ||
Hyperlipidemia | No | 26,072 | 47.3% | 26,072 | 47.3% | 1.000 |
Yes | 29,038 | 52.7% | 29,038 | 52.7% | ||
DM | No | 37,598 | 68.2% | 37,598 | 68.2% | 1.000 |
Yes | 17,512 | 31.8% | 17,512 | 31.8% | ||
CKD | No | 49,704 | 90.2% | 49,704 | 90.2% | 1.000 |
Yes | 5406 | 9.8% | 5406 | 9.8% | ||
Aspirin | No | 25,810 | 46.8% | 25,810 | 46.8% | 1.000 |
Yes | 29,300 | 53.2% | 29,300 | 53.2% | ||
Statins | No | 32,089 | 58.2% | 32,089 | 58.2% | 1.000 |
Yes | 23,021 | 41.8% | 23,021 | 41.8% | ||
ACEIs | No | 31,214 | 56.6% | 31,214 | 56.6% | 1.000 |
Yes | 23,896 | 43.4% | 23,896 | 43.4% | ||
β-Blockers | No | 16,047 | 29.1% | 16,047 | 29.1% | 1.000 |
Yes | 39,063 | 70.9% | 39,063 | 70.9% | ||
Famotidine | No | 19,841 | 36.0% | 19,841 | 36.0% | 1.000 |
Yes | 35,269 | 64.0% | 35,269 | 64.0% | ||
Spironolactone | No | 48,320 | 87.7% | 48,320 | 87.7% | 1.000 |
Yes | 6790 | 12.3% | 6790 | 12.3% | ||
Glucocorticoids | No | 5748 | 10.4% | 5748 | 10.4% | 1.000 |
Yes | 49,362 | 89.6% | 49,362 | 89.6% | ||
SSRIs | No | 44,749 | 81.2% | 44,749 | 81.2% | 1.000 |
Yes | 10,361 | 18.8% | 10,361 | 18.8% | ||
Antiviral therapy | No | 54,271 | 98.5% | 54,271 | 98.5% | 1.000 |
Yes | 839 | 1.5% | 839 | 1.5% |
Cancers | Untreated | Incidence Rate * | (95% CI) | Ranitidine | Incidence Rate * | (95% CI) |
---|---|---|---|---|---|---|
Liver cancer | 619 | 1.16 | (1.07–1.25) | 711 | 1.35 | (1.25–1.45) |
Oral Cancer | 191 | 0.36 | (0.30–0.41) | 161 | 0.30 | (0.26–0.36) |
Esophageal cancer | 82 | 0.15 | (0.12–0.19) | 101 | 0.19 | (0.16–0.23) |
Gastric cancer | 210 | 0.39 | (0.34–0.44) | 255 | 0.48 | (0.43–0.55) |
Colon cancer | 527 | 0.99 | (0.90–1.07) | 492 | 0.93 | (0.85–1.02) |
Rectal cancer | 286 | 0.53 | (0.47–0.60) | 304 | 0.58 | (0.51–0.64) |
Pancreas cancer | 93 | 0.17 | (0.14–0.21) | 121 | 0.23 | (0.19–0.27) |
Lung cancer | 575 | 1.07 | (0.98–1.16) | 649 | 1.23 | (1.14–1.33) |
Bone cancer | 3 | 0.01 | (0.00–0.02) | 4 | 0.01 | (0.00–0.02) |
Bladder cancer | 177 | 0.33 | (0.28–0.38) | 181 | 0.34 | (0.30–0.40) |
Renal cancer | 154 | 0.29 | (0.25–0.33) | 181 | 0.34 | (0.30–0.40) |
Thyroid cancer | 96 | 0.18 | (0.14–0.21) | 90 | 0.17 | (0.14–0.21) |
Skin cancer | 203 | 0.38 | (0.33–0.43) | 189 | 0.36 | (0.31–0.41) |
Breast cancer (female) | 407 | 0.76 | (0.69–0.83) | 455 | 0.86 | (0.79–0.95) |
Uterine cancer | 67 | 0.12 | (0.09–0.15) | 53 | 0.10 | (0.08–0.13) |
Cervix cancer | 166 | 0.31 | (0.27–0.36) | 155 | 0.29 | (0.25–0.34) |
Ovarian cancer | 54 | 0.10 | (0.08–0.13) | 42 | 0.08 | (0.06–0.11) |
Prostate cancer | 306 | 0.57 | (0.51–0.63) | 313 | 0.59 | (0.53–0.66) |
All cancers | 4399 | 8.49 | (8.24–8.73) | 4682 | 9.19 | (8.93–9.45) |
Liver Cancer | p | Gastric Cancer | p | Lung Cancer | p | Pancreatic Cancer | p | |
---|---|---|---|---|---|---|---|---|
Never used | 1.00 | 1.00 | 1.00 | 1.00 | ||||
90–180 DDDs * | 1.03 (0.89–1.18) | 0.690 | 1.26 (1.00–1.59) | 0.049 | 1.25 (1.09–1.44) | 0.002 | 1.64 (1.19–2.26) | 0.003 |
181–270 DDDs | 1.12 (0.93–1.34) | 0.220 | 1.13 (0.82–1.54) | 0.452 | 1.09 (0.90–1.32) | 0.403 | 1.10 (0.69–1.77) | 0.682 |
271–360 DDDs | 1.26 (0.99–1.61) | 0.064 | 1.27 (0.84–1.93) | 0.252 | 1.31 (1.02–1.68) | 0.032 | 0.92 (0.45–1.89) | 0.816 |
Over 360 DDDs | 1.42 (1.22–1.66) | <0.001 | 1.33 (1.02–1.74) | 0.037 | 1.04 (0.87–1.24) | 0.658 | 1.22 (0.80–1.85) | 0.358 |
Cancers | Famotidine | % | Ranitidine | % | Total | p-Value | HR (95% CI) | p-Value |
---|---|---|---|---|---|---|---|---|
Liver cancer | 380 | 1.1% | 442 | 1.3% | 822 | 0.032 | 1.22(1.06–1.40) | 0.005 |
Oral cancer | 125 | 0.4% | 107 | 0.3% | 232 | 0.237 | 0.87(0.67–1.12) | 0.286 |
Esophageal cancer | 52 | 0.1% | 60 | 0.2% | 112 | 0.451 | 1.19(0.82–1.72) | 0.364 |
Gastric cancer | 142 | 0.4% | 165 | 0.5% | 307 | 0.208 | 1.19(0.95–1.49) | 0.122 |
Colon cancer | 365 | 1.0% | 309 | 0.9% | 674 | 0.033 | 0.86(0.74–1.01) | 0.059 |
Rectal cancer | 193 | 0.5% | 195 | 0.6% | 388 | 0.919 | 1.03(0.84–1.26) | 0.768 |
Pancreas cancer | 66 | 0.2% | 80 | 0.2% | 146 | 0.281 | 1.25(0.90–1.73) | 0.186 |
Lung cancer | 356 | 1.0% | 400 | 1.1% | 756 | 0.116 | 1.15(1.00–1.33) | 0.052 |
Bone cancer * | n/a | n/a | n/a | n/a | n/a | n/a | 1.51(0.25–9.03) | 0.652 |
Bladder cancer | 116 | 0.3% | 117 | 0.3% | 233 | 0.948 | 1.03(0.80–1.33) | 0.830 |
Renal cancer | 98 | 0.3% | 128 | 0.4% | 226 | 0.053 | 1.33(1.02–1.73) | 0.034 |
Thyroid cancer | 71 | 0.2% | 63 | 0.2% | 134 | 0.545 | 0.89(0.64–1.25) | 0.514 |
Skin cancer | 137 | 0.4% | 137 | 0.4% | 274 | 1.000 | 1.02(0.81–1.30) | 0.842 |
All cancers | 2924 | 8.3% | 3052 | 8.7% | 5976 | 0.086 | 1.07(1.02–1.12) | 0.010 |
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Wang, C.-H.; Chen, I.-I.; Chen, C.-H.; Tseng, Y.-T. Pharmacoepidemiological Research on N-Nitrosodimethylamine-Contaminated Ranitidine Use and Long-Term Cancer Risk: A Population-Based Longitudinal Cohort Study. Int. J. Environ. Res. Public Health 2022, 19, 12469. https://doi.org/10.3390/ijerph191912469
Wang C-H, Chen I-I, Chen C-H, Tseng Y-T. Pharmacoepidemiological Research on N-Nitrosodimethylamine-Contaminated Ranitidine Use and Long-Term Cancer Risk: A Population-Based Longitudinal Cohort Study. International Journal of Environmental Research and Public Health. 2022; 19(19):12469. https://doi.org/10.3390/ijerph191912469
Chicago/Turabian StyleWang, Chun-Hsiang, I-I Chen, Chung-Hung Chen, and Yuan-Tsung Tseng. 2022. "Pharmacoepidemiological Research on N-Nitrosodimethylamine-Contaminated Ranitidine Use and Long-Term Cancer Risk: A Population-Based Longitudinal Cohort Study" International Journal of Environmental Research and Public Health 19, no. 19: 12469. https://doi.org/10.3390/ijerph191912469