PMID- 34620629
OWN - NLM
STAT- MEDLINE
DCOM- 20220304
LR  - 20220307
IS  - 1538-7755 (Electronic)
IS  - 1055-9965 (Linking)
VI  - 30
IP  - 12
DP  - 2021 Dec
TI  - Ranitidine Use and Risk of Upper Gastrointestinal Cancers.
PG  - 2302-2308
LID - 10.1158/1055-9965.EPI-21-0831 [doi]
AB  - BACKGROUND: The discovery that ranitidine is contaminated with 
      N-nitrosodimethylamine, a suspected human carcinogen, raises the hypothesis of a 
      gastrointestinal carcinogenic effect; however, evidence remains inconclusive. 
      METHODS: We used the nationwide Danish Prescription Registry to identify a cohort 
      of incident ranitidine users and two active comparator cohorts comprising users 
      of other histamine-2 receptor blockers (H2RB) and users of proton pump inhibitors 
      (PPI). All Danish adults with a first prescription of ranitidine, other H2RBs, or 
      PPIs in 1996 through 2008 were followed virtually completely through 2018 for 
      incidence of esophageal, stomach, liver, and pancreatic cancers. We used Cox 
      regression with propensity-score weighting to calculate hazard ratios and 10-year 
      cumulative risk with 95% confidence intervals. RESULTS: We ascertained 276 newly 
      diagnosed esophageal, 342 stomach, 133 hepatocellular, and 517 pancreatic cancers 
      among ranitidine users during follow-up (median 14 years). In comparison with use 
      of other H2RBs or PPIs, we found no consistent evidence of increased HRs or 
      excess 10-year cumulative risk of any upper gastrointestinal cancer following 
      ranitidine use. We observed no association after restriction to subjects with at 
      least 5 or 10 prescriptions or those with 10 prescriptions and at least 10 years 
      of follow-up. CONCLUSIONS: Our large prospective study using high-quality 
      prescription and cancer incidence data, with two active comparator groups, 
      provides no compelling evidence that ranitidine increases the risk of upper 
      gastrointestinal cancers. IMPACT: Our results, which do not support any 
      carcinogenic effect on esophagus, stomach, liver or pancreas, should be 
      reassuring for millions of concerned past users of ranitidine.
CI  - (c)2021 American Association for Cancer Research.
FAU - Adami, Hans-Olov
AU  - Adami HO
AD  - Clinical Effectiveness Group, Institute of Health and Society, University of 
      Oslo, Oslo, Norway. hadami@hsph.harvard.edu.
AD  - Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, 
      Stockholm, Sweden.
AD  - Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, 
      Massachusetts.
FAU - Trolle Andersen, Ina
AU  - Trolle Andersen I
AUID- ORCID: 0000-0002-8140-1548
AD  - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus 
      University, Aarhus, Denmark.
AD  - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
FAU - Heide-Jorgensen, Uffe
AU  - Heide-Jorgensen U
AD  - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus 
      University, Aarhus, Denmark.
AD  - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
FAU - Chang, Ellen T
AU  - Chang ET
AD  - Center for Health Sciences, Exponent, Inc., Menlo Park, California.
AD  - Sun Yat-sen University Cancer Center, Guangzhou, China.
FAU - Norgaard, Mette
AU  - Norgaard M
AD  - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus 
      University, Aarhus, Denmark.
AD  - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
FAU - Sorensen, Henrik Toft
AU  - Sorensen HT
AD  - Department of Clinical Epidemiology, Aarhus University Hospital, Aarhus 
      University, Aarhus, Denmark.
AD  - Department of Clinical Medicine, Aarhus University, Aarhus, Denmark.
AD  - Department of Epidemiology, Boston University School of Public Health, Boston, 
      Massachusetts.
LA  - eng
PT  - Journal Article
DEP - 20211007
PL  - United States
TA  - Cancer Epidemiol Biomarkers Prev
JT  - Cancer epidemiology, biomarkers & prevention : a publication of the American 
      Association for Cancer Research, cosponsored by the American Society of 
      Preventive Oncology
JID - 9200608
RN  - 0 (Histamine H2 Antagonists)
RN  - 884KT10YB7 (Ranitidine)
RN  - M43H21IO8R (Dimethylnitrosamine)
SB  - IM
EIN - Cancer Epidemiol Biomarkers Prev. 2022 Mar 1;31(3):692. PMID: 35253044
MH  - Adult
MH  - Case-Control Studies
MH  - Denmark
MH  - Dimethylnitrosamine/poisoning
MH  - Female
MH  - Gastrointestinal Neoplasms/*chemically induced
MH  - Histamine H2 Antagonists/administration & dosage/*adverse effects
MH  - Humans
MH  - Male
MH  - Middle Aged
MH  - Proportional Hazards Models
MH  - Prospective Studies
MH  - Ranitidine/administration & dosage/*adverse effects
MH  - Registries
EDAT- 2021/10/09 06:00
MHDA- 2022/03/05 06:00
CRDT- 2021/10/08 06:09
PHST- 2021/07/08 00:00 [received]
PHST- 2021/09/01 00:00 [revised]
PHST- 2021/09/30 00:00 [accepted]
PHST- 2021/10/09 06:00 [pubmed]
PHST- 2022/03/05 06:00 [medline]
PHST- 2021/10/08 06:09 [entrez]
AID - 1055-9965.EPI-21-0831 [pii]
AID - 10.1158/1055-9965.EPI-21-0831 [doi]
PST - ppublish
SO  - Cancer Epidemiol Biomarkers Prev. 2021 Dec;30(12):2302-2308. doi: 
      10.1158/1055-9965.EPI-21-0831. Epub 2021 Oct 7.