These findings are consistent with a major role of gallstones, or risk factors for gallstones, in the cause of gallbladder cancer. Additional information on whether or not screening high-risk subjects for gallstones or gallbladder cancer is needed.

During 1984-88 a population-based case-control study was carried out in the Netherlands in collaboration with the International Agency for Research on Cancer in order to investigate the role of diet in exocrine pancreatic carcinoma. A semi-quantitative food-frequency questionnaire was used to comprehensively assess usual diet about 1 year prior to diagnosis of 164 cases or interview of 480 controls. More than half of the cases were directly interviewed. After controlling for age, gender, response status, life-time cigarette consumption and dietary intake of total energy, monotonic, significantly inverse dose-response effects with estimates of daily consumption of vegetables were found. The significant inverse effect of total cooked vegetables was primarily concentrated in cruciferous vegetables. Consumption of fresh vegetables was also significantly and inversely related to risk. A monotonic, positive dose-response gradient was seen for the consumption of eggs, while consumption of fish was significantly related to risk as well. Among direct respondents, significantly inverse relationships were found for the consumption of legumes, tomatoes, cheese and fermented milk products. Inverse associations with consumption of (subgroups of) fruits were observed in women only. The monotonic, significantly inverse relationship for consumption of low-fibre vegetables and the somewhat weaker, inverse association for high-fibre vegetables in directly interviewed subjects only, may point to protective agents other than vegetable fibre. Although intake of dietary fibre and beta-carotene were both inversely related to risk, simultaneous estimation suggested that beta-carotene or other as yet unknown correlated constituents, rather than dietary fibre, might explain the inverse relationships. A significant protective effect of vitamin C was demonstrated in women but not in men. Our study suggests that, independent of smoking and dietary intake of total energy, low consumption of specific vegetables and possibly fermented milk products and high consumption of eggs and fish may have influenced the development of exocrine pancreatic cancer.

During 1984-88 a population-based case-control study was carried out in The Netherlands, in collaboration with the International Agency for Research on Cancer, to examine the possible relationship between aspects of medical history and exocrine pancreatic carcinoma in 176 cases and 487 controls. About 58% of patients were interviewed directly. In women, a significant, positive dose-response effect of height was seen (p-value trend less than 0.005). Compared with ages 14 or more, women with an early age at menarche, i.e., 11 years or less, had a 3-fold increase in risk (15 cases vs. 23 controls, OR 3.07, 95% CI 1.35 to 7.00). Other apsects of the reproductive history were not related to risk. In brief, the results of the present study support the hypothesis that, in women, early menarche and greater adult stature may be early predictors of the development of cancer of the pancreas later in life.

A multi-centre case-control study of pancreas cancer, designed to be population-based, to use a random sample of local populations as controls and to use a common protocol and core questionnaire, was conducted as the first study of the SEARCH programme of the International Agency for Research on Cancer. "Ever-smokers'' were found to be at increased risk for pancreas cancer compared with "never-smokers" consistently in all strata of gender, response status and centre. Risk of pancreas cancer was found to increase with increasing lifetime consumption of cigarettes, the relative risk rising to 2.70 (95% C.I. 1.95 to 3.74) in the highest intake category. The overall trend in risk was highly significant and the association was found consistently in each stratum of gender, response status and centre. Fifteen years had to pass from quitting cigarette smoking until the risk fell to a level compatible with that in never-smokers among the heaviest group of smokers; among the 2 lowest tertiles this happened within 5 years. Further, reported smoking habits more than I 5 years before diagnosis appeared to have no influence on pancreas-cancer risk, irrespective of amount smoked. The results are consistent with a causal role for cigarette smoking in the aetiology of pancreas cancer and illustrate that ceasing to smoke cigarettes can lead to reductions in the elevated risk of pancreas cancer produced by this habit.o 1996 Wiley-Liss, Inc.

Although reproductive factors have been shown to be related to the composition of bile and functioning of the biliary system, their relationship with biliary tract cancer has not been studied in detail. Between 1984 and 1987 we conducted a case-control study of 75 women with cancer of the biliary tract and 252 controls from the general population. An interviewer-administered questionnaire was used to collect information on reproductive history. The information was obtained from the responders themselves (direct response) or from relatives (indirect response). Our results indicate that younger age at menarche, early age at first pregnancy, higher number of pregnancies and prolonged fertility may enhance the risk of cancer of the biliary tract. Overall, increased exposure to endogenous oestrogens and progesterone constitutes a higher risk.