The results from this population-based case-control study expand upon those of earlier case-control and cohort studies that have demonstrated the association between smoking and pancreatic cancer risk. The current estimation of the overall risk of pancreatic cancer among current smokers is consistent with the 1.6- to 1.9-fold increased risk reported by other investigators [14
]. Our results support previous work that has identified a relationship between smoking intensity and duration and pancreatic cancer [14
]. After adjustment for potential confounders and suspected risk factors, we observed a two-fold increased risk of pancreatic cancer among those who smoked 40 or more pack years and similarly elevated risks were observed for those who had smoked for more than 40 years or more than 40 cigarettes per day. Unlike previous studies reporting stronger smoking-related associations among women than among men [9
], we observed similar risks for women and men. In contrast to a recent meta-analysis [14
], we did not observe an increased risk of pancreatic cancer among current cigar and/or pipe smokers. However, limited sample size restricted our examinations to participants who ever smoked pipes and cigars and who also smoked cigarettes.
The effects of smoking cessation in our study population also were similar to previously reported results [14
]. In the current study, the risk estimate among former smokers who quit 10 years prior to diagnosis or interview was similar to the decrease observed in the meta-analysis of 82 published studies [14
]. To eliminate the combined effect of short and long-term duration of years since quit, we expanded upon these analyses by investigating duration of smoking cessation in mutually exclusive groups. Our results showed that former smokers who had quit fewer than 13 years prior to diagnosis or interview had a greater than 1.6 fold elevated risk of pancreatic cancer. In contrast, former smokers who had quit 10-<15 or ≥15 years prior to diagnosis or interview had lower magnitude ORs that were not different from unity. Participants who had stopped smoking for ten or more years prior to diagnosis or interview had no increased risk of pancreatic cancer relative to nonsmokers, regardless of prior smoking intensity. In contrast, the effect of smoking cessation among those who had quit fewer than ten years prior to diagnosis or interview varied by prior smoking intensity. These results are similar to those of a previous study that examined the combined effects of smoking cessation and prior smoking intensity [31
]. Relative to current smokers, a consistent reduction in risk was observed for those former smokers who had quit for fewer than 10 to at least 25 years (in 5-year mutually exclusive groups).
Environmental tobacco smoke contains thousands of chemicals including dozens of known carcinogens [32
] yet a link between passive or secondhand smoke exposure and pancreatic cancer has not been established [33
]. In this study, passive exposure to household and workplace cigarette smoke among adults was not associated with an increased risk of pancreatic cancer, nor was childhood household exposure. We may not have expected to see an association with childhood or early adult exposure to passive smoke due to the long time interval to cancer development. This is supported by our results that demonstrate no increased risk for personal smoking after ten years of cessation.
Strengths of this study included the large sample size, the population-based design, similarity of response rates for the cases and controls, and the low case refusal rate of 8 percent. The primary reason for lost patients was aggressive disease and the high mortality rate of pancreatic cancer. Study design methods used to diminish potential selection bias included random-digit-dial to identify age-, sex- and county-matched controls from the same population from where the cases were obtained and rapid case ascertainment to identify all incident pancreatic cancer cases diagnosed in six Bay Area counties between 1994 and 1999. Trained experienced interviewers who were unaware of the study hypotheses conducted in-person interviews with participants to diminish interviewer bias and no proxy interviews were conducted to diminish recall and misclassification bias. Several limitations also should be considered when interpreting the results of this study. In particular, as in all case-control investigations, there may have been recall bias due to differential reporting of past smoking by cases versus controls because smoking could possibly have been known as a risk factor for pancreatic cancer among some individuals. However, cases and controls were equally likely to have quit smoking, suggesting that the likelihood that the observed associations were due to recall bias among the cases was low. In addition, the eligible cases who had died prior to interview may have been smokers disproportionately to nonsmokers and this may have affected the ORs resulting in bias toward the null. Multiple comparisons were made in this study, and some results could have been due to chance. However, this study was designed to test specific hypotheses related to smoking, and the outcomes of the analyses were generally consistent with previous studies supporting a causative role of cigarette smoking for pancreatic cancer.