This meta-analysis showed a statistically significant positive association between processed meat consumption and risk of pancreatic cancer. An increase in processed meat consumption of 50
g per day, about one serving, was associated with a 19% increased risk of pancreatic cancer. The positive association between processed meat consumption and pancreatic cancer risk was attenuated and not statistically significant in a sensitivity analysis excluding one of the studies (Nöthlings et al, 2005
). There was no overall association between red meat consumption and risk of pancreatic cancer. However, red meat consumption was statistically significantly positively associated with pancreatic cancer risk in men. Red meat consumption was on average higher in men than in women. If there is a threshold effect with an increased risk of pancreatic cancer only at very high levels of red meat consumption, a positive association may be more likely to be detected in men. The observed positive association in men may also be a chance finding.
Our study has some limitations. First, as a meta-analysis of observational studies, we cannot rule out that individual studies may have failed to control for potential confounders, which may introduce bias in an unpredictable direction. All studies controlled for age and smoking, but only a few studies adjusted for other potential confounders such as body mass index and history of diabetes. Another limitation is that our findings were likely to be affected by imprecise measurement of red and processed meat consumption and potential confounders. Categorisation of main exposures and confounders that are measured with error may induce misclassification and may bias the expected RR toward or away from the null value (Flegal et al, 1991
; Wacholder et al, 1991
; Wacholder, 1995
). Thus, misclassification of red and processed meat consumption and of potential confounders might have resulted in an over- or underestimation of the association between red and processed meat consumption and risk of pancreatic cancer. Finally, publication bias could be of concern in meta-analysis. Nevertheless, we found no evidence of publication bias.
We excluded one study from this meta-analysis because the exposure was total meat including poultry and fish, and only one RR (for high vs
low intake) was reported (Mills et al, 1988
). That study included only 40 pancreatic cancer deaths and therefore would not have influenced the overall RRs if the study had been included. In that study, high consumption of total meat was associated with a RR of pancreatic cancer of 2.26 (95% CI=0.72–7.12; Mills et al, 1988
A positive association between processed meat consumption and risk of pancreatic cancer is biologically plausible. Processed meats are usually preserved with nitrite and may also contain N
-nitroso compounds. N
-nitroso compounds can further be formed endogenously in the stomach from nitrite and ingested amides in foods of animal origin (Sen et al, 2000
-nitroso compounds reach the pancreas via the bloodstream and are potent carcinogens that have been shown to induce pancreatic cancer in animal models (Risch, 2003
). A population-based case–control study observed that intake of dietary nitrite from animal sources was statistically significantly positively associated with risk of pancreatic cancer in both men and women (highest vs
lowest quartile odds ratio=2.3; 95% CI=1.1–5.1, for men and odds ratio=3.2; 95% CI=1.6–6.4, for women; Coss et al, 2004
). A prospective study found that men in the highest quintile of summed nitrate/nitrite intake from processed meat had a nonsignificantly elevated risk of pancreatic cancer (hazard ratio=1.18, 95% CI=0.95–1.47; Aschebrook-Kilfoy et al, 2011
Besides processed meat consumption, humans are exposed to N
-nitroso compounds via cigarette smoking, which is an established risk factor for pancreatic cancer (Risch, 2003
). Given that the main route of human exposure to N
-nitroso compounds is cigarette smoke, the relation between processed meat consumption and pancreatic cancer risk may be modified by smoking status. Lin et al (2006)
examined the association between ham and sausage consumption and risk of pancreatic cancer by smoking status, but observed no statistically significant association in neither smokers (highest vs
lowest category RR=1.44; 95% CI=0.45–4.63) nor in nonsmokers (corresponding RR=1.16; 95% CI=0.43–3.19). However, the number of cases in the highest categories was very limited (
In conclusion, results from this meta-analysis indicated a statistically significant positive association between processed meat consumption and risk of pancreatic cancer. Red meat consumption was not associated with risk of pancreatic cancer overall, but was positively associated with risk in men. Large prospective studies with better adjustment for potential confounders are warranted to establish potential associations of red and processed meat consumption with pancreatic cancer risk. Whether the association between processed meat consumption and pancreatic cancer is modified by smoking needs further study.