Lifestyle factors and pancreatic cancer risk: A cohort study from the Swedish Twin Registry

Dear Sir, Even though pancreatic cancer is the 5th-leading cause of cancer deaths in the Western world,1 little is known about the etiology of the disease. Lifestyle and other risk factors for pancreatic cancer have been examined in many epidemiologic studies, most of which were case-control studies. The conclusions of many of these are dubious because of small sample size, low participation and use of proxy respondents. Only cigarette smoking stands out as a likely causal agent in epidemiologic studies. However, cigarette smoking can explain only about 25% of the incidence.2 Studies have also suggested that coffee, ethanol, obesity, high energy intake and high consumption of fat, carbohydrates and animal protein may be risk factors.3–5 Some studies have shown decreased risks associated with frequent consumption of fruits and vegetables, but this has not been observed consistently.3 It is possible that factors other than those that have been investigated may affect the development of pancreatic cancer. Our study examined the effects of diet, coffee, ethanol, tobacco use, BMI, physical activity and change in body weight on pancreatic cancer incidence in a cohort study of twins established in 1958 and followed by the Swedish Twin Registry. The cohort, which provided prospective information concerning exposure, included male and female same-sexed twin pairs who were born from 1886–1925 and were both living in Sweden in 1961. At the 1961 baseline, self-administered questionnaires regarding lifestyle factors were mailed to 25,778 registrees. However, 1,288 of these were found to have already died. Additional questionnaires were administered in 1963 and 1967. Our current study included 12,204 females and 9,680 males who responded to these questionnaires with information on at least some of the potential risk factors. The overall response rate to the questionnaires was 85%. Subjects with pancreatic cancer were included in the analysis only if the diagnosis was made from 1969–97. Ninety percent of the tumors were histologically confirmed. The median age at enrollment in the cohort was 56 years. Subjects were followed from exposure assessment to 1 of 3 study endpoints: diagnosis of pancreatic cancer, death or the end of the study on December 31, 1997. Cancer incidence was ascertained by record linkage to the Swedish Cancer Registry (documented to be 98% complete). 6 Death was ascertained by linkage to the Swedish Cause of Death Registry. During the follow-up period (median 16 years), there were 176 incident cases of pancreatic cancer diagnosed at a median age of 73 years. The total number of pancreatic cancer cases included in the risk analysis of each lifestyle factor is less than 176 incident cases because some subjects did not answer all the questions on the questionnaires. The internal dropout rate varied considerably between the different questions. In the questionnaires, smoking status was assessed as nonsmoker, former smoker or current smoker. Current smokers reported the number of cigarettes smoked per day and were coded as light (1–10 cigarettes/day) and regular (11 /day) based on the combination of responses to the questionnaires in 1961 and 1967. Ethanol consumption was self-reported in 1967 as amount and frequency of beer, wine and spirits intake. Ethanol consumption was coded as grams pure ethanol per month (Table I). Coffee consumption was assessed as number of cups per day (Table I). The 1967 questionnaires also included questions about the frequency of consumption of 10 food groups: fruit/vegetables, eggs, pork, beef, sausages, fish, potatoes, flour/grain products, pastry and sweets. The response alternatives were no part, a small part, a moderate part and a large part of the diet (for pastry and sweets: less than daily, daily and several times a day) . The alternatives no part and a small part were combined as low or no part for analysis. Physical activity during leisure hours was assessed as low (responses were hardly any physical exercise or light physical exercise, e.g., regular walks, light gardening) and high (responses were regular exercise or hard physical training). Physical activity at work was assessed as sedentary or physical (responses were physical or hard physical). Weight was selfreported in kilograms and height in centimeters. BMI (in kg/ m) was used as a measure of relative body weight. BMI scores were divided into 4 groups according to WHO criteria for thinness and overweight.7 BMI 18.5–24.99 was selected as the reference category. Weight was self-reported for the actual age when the subject answered the questionnaire and for ages 25 and 40. Adult weight gain was assessed by subtracting weight at age 25 years from weight at enrollment. The relative risk of pancreatic cancer was estimated through Cox proportional hazards modeling using the SAS program