Copyright ©The Author(s) 2021.
World J Gastroenterol. May 28, 2021; 27(20): 2643-2656
Published online May 28, 2021. doi: 10.3748/wjg.v27.i20.2643
Table 1 Characteristics of included studies
Study design
Sample size1
Exposure assessment
Outcome assessment
Risk estimate (95%CI)2
NOS score
Bueno de Mesquita et al[20], 1992 Netherlands82 cases and 252 controlsInterviewer administered questionnaireClinical diagnosis (histological verification, clinicians, laboratory records, registries)OR = 0.83 (0.31-2.23)Age, response status and life-time smoking of cigarettes7
Ji et al[21], 1996 China184 cases and 680 controlsInterviewer administered questionnaireRapid reporting system within cancer registryOR = 1.78 (0.91-3.47)Age, income, education, smoking, BMI, green tea drinking, respondent status, age at first birth, intake of dietary vitamin C7
Kreiger et al[10], 2001 Canada52 cases and 233 controlsMailed questionnaireCancer registryOR = 0.36 (0.13-0.96); P = 0.031Age, smoking status, BMI, tofu, dietary fat, coffee consumption, age at menarche, age at menopause, parity, estrogen replacement therapy age at first full term pregnancy8
Duell et al[22], 2005 United States241 cases and 818 controlsInterviewer administered questionnairePhysician, SEER and histologic confirmationOR = 0.95 (0.65-1.4) Age, education, smoking8
Duell et al[23], 2009 Australia, Canada, The Netherlands, Poland367 cases and 821 controlsInterviewer administered questionnaireClinicians, hospital records, pathology records, cancer registriesOR = 0.74 (0.43-1.26) Smoking, schooling, age, center, type of interview8
Zhang et al[24], 2010United States284 cases and 1096 controlsInterviewer administered questionnairePathology report confirmation3-6
Lucenteforte et al[8], 2011 Italy285 cases and 713 controlsInterviewer administered questionnaireHistologically confirmedOR = 1.04 (0.55-1.98)Study/center, age, education, area of residence, year of interview, history of diabetes, tobacco smoking7
Azeem et al[11], 2015 Czech Republic129 cases and 97 controlsInterviewer administered questionnaireHospital diagnosisOR = 0.21 (0.07-0.69)Not specified (other monitored factors)5
Masoudi et al[9], 2017Iran153 cases and 202 controlsInterviewer administered questionnairePathological reportsOR = 1.07 (0.62-1.84)Smoking status, BMI, diabetes6
Archibugi et al[25], 2020Italy253 cases and 506 controlsInterviewer administered questionnaireHistologically proven diagnosisOR = 0.52 (0.31-0.89)Age, BMI, first degree family history of pancreatic cancer, history of diabetes > 1 yr, history of chronic pancreatitis, heavy alcohol intake, smoking habit7
Skinner et al[26], 2003 United States243 cases and 115474 non-casesMailed questionnaireSelf-reported confirmed via medical records, pathology reports, death certificates, physicians, next of kin interviewRR = 1.21 (0.91-1.61) Age, time period, cigarette smoking, diabetes, BMI, height, parity8
Teras et al[27], 2005United States1959 cases among 387981 participantsSelf-administered questionnaireNational Death Index and death certificates3-8
Navarro Silvera et al[28], 2005 Canada187 cases and 89645 noncasesSelf-administered questionnaireCanadian Cancer Database and the National mortality databaseHR = 1.10 (0.81-1.50) Age, cigarette smoking intensity, cigarette smoking duration, BMI, height, study center, randomization group, parity8
Prizment et al[29], 2007 United States228 cases and 37231 noncasesSelf-administered questionnaireNational Death Index and State Health Registry of IowaHR = 0.90 (0.62-1.30)Age7
Dorjgochoo et al[30], 2009 China78 cases among 66661 participantsIn-person interview and a self-reported questionnaireShanghai Cancer registry and Shanghai Vital Statistics RegistryHR = 0.83 (0.45-1.55) Education, age at menarche, number of live births, cumulative breast feeding months, BMI, exercised regularly in past 5 yr, smoking, menopausal status, first-degree family history of cancer, other contraceptive methods9
Duell et al[31], 2013 Denmark, France, Germany, Greece, Italy, Netherlands, Norway, Spain, Sweden, United Kingdom304 cases among 328610 participantsSelf-administered questionnairePopulation cancer registries, health insurance records, hospital-based and pathology registries3-8
Lee et al[32], 2013 United States323 cases among 118164 participantsSelf-administered questionnaireCalifornia Cancer Registry3-8
Kabat et al[33], 2017 United States1003 cases and 157295 non-casesSelf-administered questionnaireSelf-reports verified by physician adjudicators through records of hospitalizations, surgeries, pathology reports and proceduresHR = 0.92 (0.80-1.06) Age, smoking status, pack-years of smoking, BMI, educational level, ethnicity, allocation to study component, diabetes7
Andersson et al[34],2018 Sweden110 cases and 16921 noncasesOn-site questionnaires and examinationsSwedish Cancer register confirmed by pathology records, autopsyHR = 0.68 (0.44-1.06)Age, smoking, alcohol consumption, BMI8
Butt et al[35], 2018 Denmark235 cases among 1.9 million womenNational Register of Medicinal Product StatisticsDanish Cancer Register and Danish National Patient RegisterRR = 0.90 (0.68-1.19) Age, year, education, PCOS, endometriosis, parity9
Michels et al[36], 2018 United States1000 cases and 195536 noncasesMailed questionnaireCancer registriesHR = 1.11 (0.97-1.28) Age, race, BMI, smoking status, alcohol use, number of cigarettes smoked per day8
Table 2 Association between the use of oral contraceptives and risk of pancreatic cancer: Subgroup analysis
Number of studies
RR (95%CI)
I2 within each subgroup
Test for subgroups differences
Study designCase-control100.85 (0.64-1.14)60% (P = 0.008)P = 0.92
Cohort110.84 (0.70-1.00)85% (P < 0.00001)
Source of controls in case-control studiesPopulation60.75 (0.47-1.21)63% (P = 0.02)P = 0.47
Hospital40.94 (0.64-1.39)61% (P = 0.06)
Number of pancreatic cancer cases< 20080.80 (0.56-1.14)66% (P = 0.004)P = 0.77
≥ 200130.85 (0.71-1.00)83% (P < 0.00001)
Assessed study qualityNOS ≤ 790.93 (0.75-1.17)56% (P = 0.02)P = 0.33
NOS > 7120.80 (0.66-0.98) 84% (P < 0.00001)
Geographic region1Europe70.67 (0.51-0.88) 55% (P = 0.04)P = 0.07
Americas100.91 (0.74-1.11)86% (P < 0.00001)
Asia31.14 (0.76-1.73)27% (P = 0.25)
Menopausal status Premenopausal10.90 (0.68-1.19)N/A0.90
Postmenopausal 40.88 (0.79-0.98)17% (P = 0.31)