Table 2 The association between PPI use and the risk of gastric cancer in the PCCIU database.

From: Use of proton pump inhibitors and histamine-2 receptor antagonists and risk of gastric cancer in two population-based studies

   

Unadjusted

Adjusteda

Fully adjustedb

 

Case, n (%)

Control, n (%)

OR (95% CI)

OR (95% CI)

OR (95% CI)

PPI main analysis (removing 1 year before index)

  PPI user vs. non-user

329/1119 (29.4)

1213/5394 (22.5)

1.45 (1.25, 1.68)

1.48 (1.26, 1.73)

1.49 (1.24, 1.80)

  Male only

167/639 (26.1)

668/3082 (21.7)

1.29 (1.05, 1.58)

1.30 (1.05, 1.61)

1.26 (0.97, 1.62)

  Female only

162/480 (33.8)

545/2312 (23.6)

1.66 (1.33, 2.06)

1.74 (1.38, 2.19)

1.84 (1.38, 2.47)

  High-dose PPI user vs. non-user

33/1119 (3.0)

109/5394 (2.0)

1.40 (0.94, 2.10)

1.40 (0.93, 2.12)

1.23 (0.76, 1.97)

Dose–response analysis (removing 1 year before index)

  1–183 DDDs vs. non-user

141/1119 (12.6)

441/5394 (8.2)

1.74 (1.41, 2.14)

1.77 (1.43, 2.19)

1.84 (1.43, 2.38)

  184–365 DDDs vs. non-user

43/1119 (3.8)

163/5394 (3.0)

1.41 (1.00, 1.99)

1.48 (1.04, 2.09)

1.49 (0.97, 2.28)

  366–1095 DDDs vs. non-user

81/1119 (7.2)

352/5394 (6.5)

1.21 (0.94, 1.56)

1.23 (0.94, 1.59)

1.20 (0.89, 1.64)

  ≥1096 DDDs vs. non-user

64/1119 (5.7)

257/5394 (4.8)

1.32 (0.98, 1.77)

1.31 (0.97, 1.77)

1.30 (0.91, 1.85)

  P value for the trend

  

0.003

0.004

0.026

  1–6 prescriptions vs. non-user

153/1119 (13.7)

482/5394 (13.7)

1.71 (1.40, 2.10)

1.74 (1.42, 2.14)

1.85 (1.44, 2.37)

  6–12 prescriptions vs. non-user

44/1119 (3.9)

167/5394 (3.1)

1.42 (1.01, 2.00)

1.46 (1.04, 2.07)

1.39 (0.91, 2.13)

  12–36 prescriptions vs. non-user

90/1119 (8.0)

366/5394 (6.8)

1.31 (1.02, 1.68)

1.33 (1.04, 1.72)

1.35 (1.00, 1.82)

  ≥36 prescriptions vs. non-user

42/1119 (3.7)

198/5394 (3.7)

1.07 (0.75, 1.53)

1.06 (0.74, 1.52)

0.97 (0.64, 1.47)

  P value for the trend

  

0.008

0.010

0.073

PPI user vs. non-user when removing prescriptions in specific duration

  Removing 2 years before index

212/862 (24.6)

878/4126 (21.3)

1.20 (1.00, 1.43)

1.19 (0.99, 1.43)

1.13 (0.91, 1.40)

  Removing 3 years before index

137/644 (21.3)

620/3062 (20.3)

1.04 (0.84, 1.28)

1.04 (0.83, 1.29)

1.03 (0.80, 1.33)

  Removing 4 years before index

87/474 (18.3)

421/2235 (18.8)

0.93 (0.71, 1.21)

0.92 (0.70, 1.21)

0.89 (0.65, 1.22)

  Removing 5 years before index

55/345 (15.9)

267/1611 (16.6)

0.90 (0.65, 1.25)

0.90 (0.64, 1.26)

0.82 (0.55, 1.22)

PPI user in specific time periods before index date/cancer diagnosis date

  0–1 y before indexc

664/1119 (59.3)

1088/5394 (20.2)

6.32 (5.44, 7.33)

6.79 (5.82, 7.91)

7.04 (5.75, 8.61)

  1–2 y before indexd

259/1119 (23.2)

926/5394 (17.2)

1.45 (1.23, 1.70)

1.47 (1.25, 1.74)

1.51 (1.23, 1.84)

  2–3 y before indexe

165/862 (19.1)

670/4126 (16.2)

1.20 (0.99, 1.46)

1.20 (0.98, 1.47)

1.15 (0.90, 1.46)

  3–4 y before indexf

107/644 (16.6)

481/3062 (15.7)

1.04 (0.82, 1.31)

1.02 (0.81, 1.30)

1.00 (0.76, 1.33)

  4–5 y before indexg

68/474 (14.4)

329/2235 (14.7)

0.93 (0.70, 1.24)

0.92 (0.69, 1.23)

0.96 (0.68, 1.35)

PPI new user vs. PPI non-new userh

376/1119 (33.6)

235/5394 (4.4)

10.93 (9.01,13.25)

11.11 (9.14, 13.51)

10.98 (8.47, 14.23)

Omeprazole user vs. non-user

  Removing 1 year before the index

201/1119 (18.0)

774/5394 (14.4)

1.30 (1.09, 1.55)

1.29 (1.07, 1.54)

1.21 (0.97, 1.50)

  Removing 2 years before the index

123/862 (14.3)

548/4126 (13.3)

1.06 (0.85, 1.32)

1.03 (0.82, 1.29)

0.92 (0.70, 1.20)

  Removing 3 years before the index

78/644 (12.1)

373/3062 (12.2)

0.95 (0.73, 1.24)

0.95 (0.72, 1.25)

0.89 (0.65, 1.23)

Lansoprazole user vs. non-user

  Removing 1 year before the index

169/1119 (15.1)

610/5394 (11.3)

1.40 (1.16, 1.69)

1.42 (1.17, 1.73)

1.49 (1.18, 1.88)

  Removing 2 years before the index

114/862 (13.2)

447/4126 (10.8)

1.24 (0.99, 1.56)

1.24 (0.99, 1.57)

1.27 (0.97, 1.66)

  Removing 3 years before the index

75/644 (11.7)

319/3062 (10.4)

1.11 (0.85, 1.46)

1.12 (0.84, 1.48)

1.17 (0.85, 1.62)

Sensitivity analysis (PPI user vs. non-user)

  Additionally adjusted for H2RAi

329/1119 (29.4)

1213/5394 (22.5)

1.45 (1.25, 1.68)

1.41 (1.20, 1.65)

1.43 (1.18, 1.73)

  PPI user vs. H2RA userj

329/431 (76.3)

1213/1604 (75.6)

1.18 (0.85, 1.65)

1.24 (0.88, 1.75)

1.34 (0.85, 2.09)

  Adjusted for lifestyle using multiple imputationk

329/1119 (29.4)

1213/5394 (22.5)

1.45 (1.25, 1.68)

1.48 (1.26, 1.73)

1.47 (1.26, 1.72)

  Additionally not adjusted for peptic ulcer and oesophagitisl

329/1119 (29.4)

1213/5394 (22.5)

1.45 (1.25, 1.68)

1.45 (1.25, 1.69)

1.44 (1.20, 1.74)

  1. aStudy matched on age, sex and general practice, and the model contains obesity, comorbidities in the exposure period (including diabetes, coronary heart disease, myocardial infarction, heart failure, peripheral vascular disease, cerebrovascular disease, cerebrovascular accident, chronic obstructive pulmonary disease, mental illness, liver disease, peptic ulcer and oesophagitis) and other medication uses in the exposure period (statins and aspirin).
  2. bAdditionally adjusted for alcohol and smoking.
  3. cMedication use in the year prior to diagnosis/index date restricted to individuals with at least 3 years of records.
  4. dMedication use in the year from 2 to 1 year prior to diagnosis/index date restricted to individuals with at least 3 years of records.
  5. eMedication use in the year from 3 to 2 years prior to diagnosis/index date restricted to individuals with at least 4 years of records.
  6. fMedication use in the year from 4 to 3 years prior to diagnosis/index date restricted to individuals with at least 5 years of records.
  7. gMedication use in the year from 5 to 4 years prior to diagnosis/index date restricted to individuals with at least 6 years of records.
  8. hProportion of cases and controls who used PPI in the year before diagnosis and who had not previously used PPI.
  9. iAdditionally adjusted for H2RA.
  10. jUsing only H2RA users as an active comparator.
  11. kUsing multiple imputation to adjust for alcohol and smoking.
  12. lRemoving the peptic ulcer and oesophagitis adjustment from the main model.
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