Systematic review of the relation between smokeless tobacco and cancer of the pancreas in Europe and North America

Background: Recent reviews claiming smokeless tobacco increases pancreatic cancer risk appear not to have considered all available epidemiological evidence; nor were meta-analyses included. We present a systematic review of studies from North America and Europe, since data are lacking from other continents. Risk is also difficult to quantify elsewhere due to the various products, compositions and usage practices involved. Methods: Epidemiological studies were identified that related pancreatic cancer to use of snuff, chewing tobacco or unspecified smokeless tobacco. Study details and effect estimates (relative risks or odds ratios) were extracted, and combined by meta-analyses. Results: Nine North American and two Scandinavian studies were identified. Reporting was limited in four studies, so only seven were included in meta-analyses, some providing results for never smokers, some for the overall population of smokers and non-smokers, and some for both. Giving preference to study-specific estimates for the overall population, if available, and for never smokers otherwise, the random-effects estimate for ever smokeless tobacco use was 1.03 (95% confidence interval 0.71-1.49) based on heterogeneous estimates from seven studies. The estimate varied little by continent, study type, or type of smokeless tobacco. Giving preference to estimates for never smokers, if available, and overall population estimates otherwise, the estimate was 1.14 (0.67-1.93), again based on heterogeneous estimates. Estimates varied (p = 0.014) between cohort studies (1.75, 1.20-2.54) and case-control studies (0.84, 0.36-1.97). The value for cohort studies derived mainly from one study, which reported an increase for never smokers (2.0, 1.2-3.3), but not overall (0.9, 0.7-1.2). This study also contributed to increases seen for snuff use and for European studies, significant only in fixed-effect analyses. The studies have various weaknesses, including few exposed cases, reliance in cohort studies on exposure recorded at baseline, poor control groups in some case-control studies, and lack of a dose-response. Publication bias, with some negative studies not being presented, is also possible. Conclusion: At most, the data suggest a possible effect of smokeless tobacco on pancreatic cancer risk. More evidence is needed. If any risk exists, it is highly likely to be less than that from smoking.