Table 3.
Smokeless tobacco use and risk of cancers, ischaemic heart disease, and stroke—studies included in meta-analysis
| Country | Study period | Study design | Exposure status | Inclusion of cigarette/alcohol users | Outcome | Odds ratio/relative risk (95% CIs) | Comments | Quality assessment (NOS)a | Reference |
|---|---|---|---|---|---|---|---|---|---|
| Cancers | |||||||||
| India | 2001–2004 | Case–control | SLT with or without additives | No/no | Oral cancer | 0.49 (0.32–0.75) | Exclusive SLT users |
Selection**** Comparability** Exposure* |
[36] |
| India | 1996–1999 | Case–control | Ever SLT users | Yes/yes | Oral cancer | 7.31 (3.79–14.1) | Never drinkers adjusted for smoking |
Selection**** Comparability** Exposure* |
[37] |
| 9.19 (4.38–19.28) | Never smokers adjusted for alcohol | ||||||||
| India | 1982–1992 | Case–control | Tobacco quid chewing | Yes/no | Oral cancer | 5.80 (3.60–9.34) | Adjusted for smoking |
Selection*** Comparability* Exposure* |
[38] |
| Pharyngeal cancer | 1.20 (0.80–1.80) | ||||||||
| Lung cancer | 0.70 (0.40–1.22) | ||||||||
| India | Not clear | Case–control | Chewing tobacco | No/no | Oral cancer | 10.75 (6.58–17.56) | Exclusive SLT users |
Selection** Comparability* Exposure0 |
[39] |
| India | 1990–1997 | Cohort | Current SLT users | No/no | Oral cancer | 5.50 (3.30–9.17) | Exclusive SLT users |
Selection**** Comparability* Outcome** |
[40] |
| Former SLT users | 9.20 (4.60–18.40) | ||||||||
| India | 1990–1997 | Cohort | Current SLT user | Yes/yes | Oral cancer | 2.40 (1.70–3.39) | Adjusted for smoking and alcohol |
Selection**** Comparability* Outcome*** |
[41] |
| Former SLT users | 2.10 (1.30–3.39) | ||||||||
| India | Not clear | Case–control | Ever SLT users | No/no | Oral cancer | 4.23 (3.11–5.75) | Exclusive SLT users |
Selection*** Comparability** Exposure0 |
[42] |
| Pharyngeal cancer | 2.42 (1.74–3.37) | ||||||||
| Laryngeal cancer | 2.80 (2.07–3.79) | ||||||||
| Oesophageal cancer | 1.55 (1.15–2.07) | ||||||||
| India | 1968 | Case–control | Tobacco | Yes/no | Oral cancer | 4.63 (3.50–6.14) | Exclusive chewers and non-chewers data available |
Selection*** Comparability** Exposure0 |
[43] |
| Pharyngeal cancer | 3.09 (2.31–4.13) | ||||||||
| Laryngeal cancer | 2.29 (1.72–3.05) | ||||||||
| Oesophageal cancer | 3.82 (2.84–5.13) | ||||||||
| India | 2005–2006 | Case–control | Tobacco flakes | Yes/yes | Oral cancer | 7.60 (4.90–11.79) | Adjusted for smoking and alcohol |
Selection**** Comparability** Exposure* |
[44] |
| Gutkha | 12.70 (7.00–23.04) | ||||||||
| Mishiri | 3.00 (1.90–4.74) | ||||||||
| India | Not clear | Case–control | Chewing tobacco | Yes/yes | Oral cancer | 5.00 (3.60–6.94) | Adjusted for smoking and alcohol |
Selection**** Comparability* Exposure* |
[45] |
| India | 1982–1984 | Case–control | Chewing tobacco | Yes/no | Oral cancer | 10.20 (2.60–40.02) | Adjusted for smoking |
Selection*** Comparability** Exposure* |
[46] |
| India | 1980–1984 | Case–control | SLT users | No/no | Oral cancer | 1.99 (1.41–2.81) | Exclusive SLT users |
Selection** Comparability0 Exposure* |
[47] |
| India | 1952–1954 | Case–control | Chewing tobacco | No/no | Oral cancer | 4.85 (2.32–10.14) | Exclusive SLT users |
Selection*** Comparability** Exposure0 |
[48] |
| Pharyngeal cancer | 2.02 (0.94–4.33) | ||||||||
| Laryngeal cancer | 0.76 (0.37–1.56) | ||||||||
| India | 1983–1984 | Case–control | Snuff (males only) | Yes/yes | Oral cancer | 2.93 (0.98–8.76) | Adjusted for smoking and alcohol; adjusted effect size is only among males |
Selection*** Comparability0 Exposure* |
[49] |
| India | Not given | Case–control | Tobacco chewing | Yes/yes | Oropharyngeal cancer | 7.98 (4.11–13.58)b | Adjusted for smoking and alcohol |
Selection*** Comparability** Exposure0 |
[50] |
| India | 1991–2003 | Case–control | Chewing tobacco | No/no | Oral cancer | 5.88 (3.66–7.93) | Exclusive SLT users |
Selection**** Comparability** Exposure** |
[51] |
| India | 1950–1962 | Case–control | Tobacco with or without paan or lime | Yes/no | Oral and oropharyngeal cancer | 41.90 (34.20–51.33) | Exclusive chewer data available; data of habit was not available for the whole cohort |
Selection** Comparability** Exposure0 |
[52] |
| Pakistan | 1996–1998 | Case–control | Naswar | Yes/yes | Oral cancer | 9.53 (1.73–52.50) | Adjusted for smoking and alcohol |
Selection*** Comparability** Exposure* |
[53] |
| Paan with tobacco | 8.42 (2.31–30.69) | ||||||||
| Sweden | 1973–2002 | Cohort | Snus | Yes/yes | Oral and pharyngeal cancer combined | 3.10 (1.50–6.41) | Adjusted for smoking and alcohol |
Selection** Comparability** Outcome*** |
[54] |
| India | 1993–1999 | Case–control | Chewing tobacco | Yes/yes | Oral cancer | 5.05 (4.26–5.99) | Adjusted for smoking and alcohol |
Selection*** Comparability** Exposure* |
[55] |
| Pharyngeal cancer | 1.83 (1.43–2.34) | ||||||||
| Oesophageal cancer | 2.06 (1.62–2.62) | ||||||||
| Norway | 1966–2001 | Cohort | Chewing tobacco plus oral snuff | No/no | Oral cancer | 1.10 (0.50–2.42) | Adjusted for smoking, might be confounded by alcohol use |
Selection*** Comparability* Outcome*** |
[56] |
| Oesophageal cancer | 1.40 (0.61–3.21) | ||||||||
| Pancreatic cancer | 1.67 (1.12–2.49) | ||||||||
| Lung cancer | 0.80 (0.61–1.05) | ||||||||
| Sweden | 1988–1991 | Case–control | Oral snuff | Yes/yes | Oral cancer | 1.40 (0.80–2.45) | Adjusted for smoking and alcohol |
Selection** Comparability** Exposure* |
[57] |
| Laryngeal cancer | 0.90 (0.50–1.62) | ||||||||
| Oesophageal cancer | 1.20 (0.70–2.06) | ||||||||
| Pharyngeal cancer | 0.70 (0.40–1.22) | ||||||||
| Sweden | 1969–1992 | Cohort | Snus | No/no | Oral cancer | 0.80 (0.40–1.60) | Exclusive SLT users |
Selection*** Comparability* Outcome*** |
[58] |
| Lung cancer | 0.80 (0.50–1.28) | ||||||||
| Pancreatic cancer | 2.00 (1.20–3.33) | ||||||||
| Sweden | 2000–2004 | Case–control | Oral snuff | Yes/yes | Oral cancer | 0.70 (0.30–1.63) | Adjusted for smoking and alcohol |
Selection*** Comparability** Exposure** |
[59] |
| Sweden | 1980–1989 | Case–control | Oral snuff | Yes/yes | Oral cancer | 0.80 (0.50–1.28) | Adjusted for smoking and alcohol |
Selection** Comparability** Exposure*** |
[60] |
| USA | 1972–1983 | Case–control | Oral snuff | Yes/yes | Oral cancer | 0.80 (0.40–1.60) | Not clear if adjusted for smoking and alcohol |
Selection** Comparability0 Exposure* |
[61] |
| Chewing tobacco | 1.00 (0.70–1.43) | ||||||||
| USA | Not given | Case–control | SLT use | Yes/yes | Oral cancer | 0.90 (0.38–2.13) | Adjusted for smoking and alcohol |
Selection*** Comparability** Exposure* |
[10] |
| Pharyngeal cancer | 1.59 (0.84–3.01) | ||||||||
| Laryngeal cancer | 0.67 (0.19–2.36) | ||||||||
| India | 2001–2004 | Case–control | Chewing tobacco | No/no | Pharyngeal cancer | 3.18 (1.92–5.27) | Exclusive SLT users |
Selection*** Comparability** Exposure* |
[62] |
| Laryngeal cancer | 0.95 (0.52–1.74) | ||||||||
| Pakistan | 1998–2002 | Case–control | Snuff dipping | No/no | Oesophageal cancer | 4.10 (1.30–12.93) | Adjusted for areca nut |
Selection*** Comparability** Exposure** |
[63] |
| Quid with tobacco | 14.20 (6.40–31.50) | ||||||||
| India | 2008–2012 | Case–control | Nass chewing | No/no | Oesophageal cancer | 2.88 (2.06–4.03) | Exclusive SLT users |
Selection*** Comparability** Exposure** |
[64] |
| Gutkha chewing | 2.87 (0.87–9.47) | ||||||||
| India | 2007–2011 | Case–control | Oral snuff | Yes/yes | Oesophageal cancer | 3.86 (2.46–6.06) | Adjusted for smoking and alcohol |
Selection** Comparability** Exposure* |
[65] |
| India | 2011–2012 | Case–control | Chewing tobacco | Yes/yes | Oesophageal cancer | 2.63 (1.53–4.52) | Adjusted for smoking and alcohol |
Selection*** Comparability** Exposure* |
[66] |
| Sweden | 1995–1997 | Case–control | Oral snuff | Yes/yes | Oesophageal adenocarcinoma | 1.20 (0.70–2.06) | Adjusted for smoking and alcohol |
Selection*** Comparability** Exposure* |
[67] |
| Squamous cell carcinoma | 1.40 (0.90–2.18) | ||||||||
| Sweden | 1969–1993 | Cohort | Oral snuff | Yes/no | Oesophageal adenocarcinoma | 1.30 (0.80–2.11) | Adjusted for smoking |
Selection** Comparability* Outcome** |
[68] |
| Squamous cell carcinoma | 1.20 (0.80–1.80) | ||||||||
| Sweden | 1974–1985 | Cohort | SLT users | No/NA | Lung cancer | 0.90 (0.20–4.05) | Adjusted for age, region of origin |
Selection*** Comparability* Outcome** |
[69] |
| Morocco | 1996–1998 | Case–control | SLT users | Yes/no | Lung cancer | 1.05 (0.28–3.94) | Adjusted for smoking |
Selection** Comparability** Exposure** |
[70] |
| USA | 1977–1984 | Case–control | SLT users | Yes/no | Oesophageal cancer | 1.20 (0.10–14.40) | Adjusted for smoking |
Selection*** Comparability** Exposure** |
[71] |
| USA | 1986–1989 | Case–control | SLT users | Yes/no | Pancreatic cancer | 1.40 (0.50–3.92) | Adjusted for smoking |
Selection*** Comparability* Exposure** |
[72] |
| USA | 2000–2006 | Case–control | Chewing tobacco | Yes/yes | Pancreatic cancer | 0.60 (0.30–1.20) | Adjusted for smoking and alcohol |
Selection**** Comparability** Exposure* |
[73] |
| Oral snuff | 0.50 (0.10–2.50) | ||||||||
| Pakistan | 2014–2015 | Case–control | Ever use of naswar | Yes/yes | Oral cancer | 21.20 (8.40–53.8) | Adjusted for smoking; restricted control for alcohol due to cultural sensitivity |
Selection**** Comparability** Exposure*** |
[74] |
| India | March–July, 2013 | Case–control | Gutkha | Yes/yes | Oral cancer | 5.10 (2.00–10.30) | Adjusted for smoking and alcohol |
Selection*** Comparability* Exposure** |
[75] |
| Chewing tobacco | 6.00 (2.30–15.70) | ||||||||
| Supari with tobacco | 11.40 (3.40–38.20) | ||||||||
| Quid with tobacco | 6.40 (2.60–15.50) | ||||||||
| Pakistan | 1996–1998 | Case–control | Quid with tobacco | Yes/yes | Oral cancer | 15.68 (3.00–54.90) | Adjusted for smoking and alcohol |
Selection** Comparability* Exposure*** |
[76] |
| Cardiovascular diseases (ischaemic heart disease and stroke) | |||||||||
| 52 countries | 1999–2003 | Case–control | Chewing tobacco | Yes/yes | Myocardial infarction | 1.57 (1.24–1.99) | Adjusted for smoking, diet, diabetes, abdominal obesity, exercise, hypertension |
Selection**** Comparability** Exposure* |
[35] |
| Pakistan | 2005–2011 | Case–control | Dippers (Naswar) | No/NA | Myocardial infarction | 1.46 (1.21–1.78) | Adjusted for age, gender, region, ethnicity, diet, socioeconomic status |
Selection**** Comparability** Exposure** |
[77] |
| Chewers (Paan/Supari/Gutkha) | 1.71 (1.46–2.00) | ||||||||
| Bangladesh | 2006–2007 | Case–control | Ever SLT users | Yes/NA | Myocardial infarction, angina pectoris | 2.80 (1.10–7.30) | Adjusted for age, gender, smoking, hypertension | Selection** Comparability** Exposure** | [78] |
| Bangladesh | 2010 | Case–control | Ever SLT users | No/NA | Myocardial infarction, angina pectoris | 0.77 (0.52–1.13) | Adjusted for age, gender, area of residence, hypertension, diabetes, stress | Selection*** Comparability** Exposure* | [79] |
| India | 2013 | Case–control | Current SLT users | Yes/yes | Stroke | 1.50 (0.80–2.79) | Adjusted for age, smoking, alcohol, diabetes, hypertension | Selection** Comparability** Exposure* | [80] |
| Sweden | 1989–1991 | Case–control | Current snuff users | No/NA | Myocardial infarction | 0.89 (0.62–1.29) | Adjusted for age | Selection**** Comparability** Exposure* | [81] |
| Sweden | 1991–1993 | Case–control | Current snuff users | No/NA | Myocardial infarction | 0.58 (0.35–0.94) | Adjusted for heredity, education, marital status, hypertension, diabetes, cholesterol | Selection**** Comparability** Exposure** | [82] |
| Sweden | 1985–2000 | Case–control | Current snuff users | No/NA | Stroke | 0.87 (0.41–1.83) | Adjusted for education, marital status, diabetes, hypertension, cholesterol | Selection**** Comparability** Exposure** | [83] |
| Sweden | 1998–2005 | Case–control | Current snuff users | No/NA | Myocardial infarction | 0.73 (0.35–1.50) | Adjusted for age, hospital catchment area | Selection*** Comparability** Exposure** | [84] |
| Former snuff users | 1.20 (0.46–3.10) | ||||||||
| Sweden | 1988–2003 | Cohort | Current use of snuff | No/NA | Ischaemic heart disease | 0.77 (0.51–1.15) | Adjusted for age, socioeconomic status, residential area, self-reported health, longstanding illnesses, physical activity | Selection*** Comparability** Outcome*** | [85] |
| Stroke | 1.07 (0.65–1.77) | ||||||||
| Sweden | 1978–2004 | Cohort | Ever snuff users | No/NA | Myocardial infarction | 0.99 (0.90–1.10) | Adjusted for age, BMI, region of residence | Selection** Comparability** Outcome*** | [86] |
| Sweden | 1985–1999 | Case–control | Current snuff users | No/NA | Myocardial infarction | 0.82 (0.46–1.43) | Adjusted for BMI, leisure time, physical activity, education, cholesterol | Selection**** Comparability** Exposure* | [87] |
| Former snuff users | 0.66 (0.32–1.34) | ||||||||
| Sweden | 1978–2003 | Cohort | Ever snuff users | No/NA | Stroke | 1.02 (0.92–1.13) | Adjusted for age, BMI, region of residence | Selection** Comparability** Outcome*** | [88] |
| Sweden | 1998–2005 | Cohort | Current snuff users | No/NA | Ischaemic heart disease | 0.85 (0.51–1.42) | Adjusted for age, hypertension, diabetes, cholesterol | Selection*** Comparability** Outcome* | [89] |
| Former snuff users | 1.07 (0.56–2.04) | ||||||||
| Current snuff users | Stroke | 1.18 (0.67–2.08) | |||||||
| Former snuff users | 1.35 (0.65–2.82) | ||||||||
| Sweden | 1991–2004 | Cohort | Current snuff users | No/NA | Myocardial infarction | 0.75 (0.30–1.87) | Adjusted for age, marital status, occupation, diabetes, BMI, hypertension, physical activity | Selection*** Comparability** Outcome** | [90] |
| Stroke | 0.59 (0.20–1.50) | ||||||||
BMI body mass index, NA not applicable, NOS Newcastle-Ottawa Scale, SLT smokeless tobacco
aNOS for assessing the quality of non-randomised studies in meta-analyses based on selection, comparability, and exposure/outcome. Number of stars (*) indicates the number of criteria met for each of these three categories
bEffect sizes are for oral and pharyngeal cancers combined and were included in the meta-analysis for oral cancer only