Higher Meat Intake Is Positively Associated With Higher Risk of Developing Pancreatic Cancer in an Age-Dependent Manner and Are Modified by Plasma Antioxidants: A Prospective Cohort Study (EPIC-Norfolk) Using Data From Food Diaries.

OBJECTIVE: Carcinogens in meat may be involved in pancreatic carcinogenesis. Meat intake was investigated using 7-day food diaries and according to factors potentially influencing carcinogenesis: age, cooking method, and antioxidants. METHODS: Twenty-three thousand one hundred thirty-three participants in the European Prospective Investigation of Cancer-Norfolk cohort study completed 7-day food diaries and were followed up. Meat intakes were compared with controls and hazard ratios (HRs) calculated. RESULTS: Eighty-six participants developed pancreatic cancer. If younger than 60 years at recruitment, all quintiles of red meat (Q1 vs Q5; HR, 4.62; 95% confidence interval [CI], 0.96-22.30; P = 0.06) and processed meat (Q1 vs Q5; HR, 3.73; 95% CI, 0.95-14.66; P = 0.06) were nonsignificantly positively associated, with significant trends across quintiles (HRtrend, 1.33; 95% CI, 1.01-1.77 and HRtrend, 1.37; 95% CI, 1.04-1.82, respectively). Red meat's effect was attenuated by higher, but not lower, plasma vitamin C (HR, 1.06; 95% CI, 0.69-1.63 vs HR, 1.84; 95% CI, 1.09-3.14) and for processed meat (HR, 1.07; 95% CI, 0.71-1.63 vs HR, 1.80; 95% CI, 1.10-2.96). A nonstatistically significant risk was observed for high-temperature cooking methods in younger people (HR, 4.68; 95% CI, 0.63-34.70; P = 0.13). CONCLUSIONS: Red and processed meats may be involved in pancreatic carcinogenesis.

Investigating Physical Activity in the Etiology of Pancreatic Cancer: The Age at Which This Is Measured Is Important and Is Independent of Body Mass Index.

OBJECTIVES: There are plausible biological mechanisms for how increased physical activity (PA) may prevent pancreatic cancer, although findings from epidemiological studies are inconsistent. We investigated whether the risk is dependent on the age at which PA is measured and if independent of body mass index (BMI). METHODS: A total of 23,639 participants, aged 40 to 74 years, were recruited into the EPIC-Norfolk (European Prospective Investigation of Cancer) cohort study between 1993 and 1997 and completed validated questionnaires on PA. The cohort was monitored for pancreatic cancer development, and hazard ratios (HRs) were estimated and adjusted for covariates. RESULTS: Within 17 years, 88 participants developed pancreatic cancer (55% female). There was no association between PA and risk in the cohort (HR trend, 1.06; 95% confidence interval [CI], 0.86-1.29). However, in participants younger than 60 years, higher PA was associated with decreased risk (highest vs lowest category HR, 0.27; 95% CI, 0.07-0.99). Higher PA was not inversely associated when older than 60 years (HR trend, 1.23; 95% CI, 0.96-1.57). Including BMI in all models produced similar estimates. CONCLUSIONS: The reasons why PA in younger, but not older, people may prevent pancreatic cancer need to be investigated. Physical activity may operate through mechanisms independent of BMI. If this association is causal, 1 in 6 cases might be prevented by encouraging more PA.

Dietary antioxidants and the aetiology of pancreatic cancer: a cohort study using data from food diaries and biomarkers.

OBJECTIVE: To investigate whether the dietary antioxidants vitamins C and E, selenium and zinc decrease the risk of developing pancreatic cancer, for the first time using 7-day food diaries, the most accurate dietary methodology in prospective work. DESIGN: 23,658 participants, aged 40-74 years, recruited into the EPIC-Norfolk Study completed 7-day food diaries which recorded foods, brands and portion sizes. Nutrient intakes were calculated in those later diagnosed with pancreatic cancer and in 3970 controls, using a computer program with information on 11,000 foods. Vitamin C was measured in serum samples. The HRs of developing pancreatic cancer were estimated across quartiles of intake and thresholds of the lowest quartile (Q1) against a summation of the three highest (Q2-4). RESULTS: Within 10 years, 49 participants (55% men), developed pancreatic cancer. Those eating a combination of the highest three quartiles of all of vitamins C and E and selenium had a decreased risk (HR=0.33, 95% CI 0.13 to 0.84, p<0.05). There were threshold effects (Q2-4 vs Q1) for selenium (HR=0.49, 95% CI 0.26 to 0.93, p<0.05) and vitamin E (HR=0.57, 95% CI 0.29 to 1.09, p<0.10). The HRs of quartiles for antioxidants, apart from zinc, were <1, but not statistically significant. For vitamin C, there was an inverse association with serum measurements (HR trend=0.67, 95% CI 0.49 to 0.91, p=0.01), but the threshold effect from diaries was not significant (HR=0.68, 95% CI 0.37 to 1.26). CONCLUSION: The results support measuring antioxidants in studies investigating the aetiology of pancreatic cancer. If the association is causal, 1 in 12 cancers might be prevented by avoiding the lowest intakes.

The aetiology of symptomatic gallstones quantification of the effects of obesity, alcohol and serum lipids on risk. Epidemiological and biomarker data from a UK prospective cohort study (EPIC-Norfolk).

OBJECTIVE: The development of gallstones is influenced by obesity and alcohol. This study aimed to precisely quantify these risks and investigate whether the aetiological mechanism may involve serum lipids, for the first time using a European prospective cohort study. METHODS: The European Prospective Investigation into Cancer-Norfolk, recruited 25 639 men and women, aged 40 to 74 years, between 1993 and 1997. At enrolment weight, height and alcohol intake were recorded and nonfasting blood samples taken to measure serum triglycerides, cholesterol, high-density lipoproteins and low-density lipoproteins. The cohort was monitored for 14 years for symptomatic gallstones. Cox regression estimated sex-specific hazard ratios (HRs) for symptomatic gallstones adjusted for covariates. RESULTS: Symptomatic gallstones developed in 296 people (67.9% women). For each additional unit of BMI, the HR in men was 1.08 [95% confidence interval (CI)=1.02-1.14]; in women the HR was 1.08 (95% CI=1.06-1.11). Every unit of alcohol consumed per week decreased risk in men by 3% (HR=0.97, 95% CI=0.95-0.99) with no effect in women. Serum triglycerides increased risk in men (highest vs. lowest quarter HR=2.02, 95% CI=1.03-3.98) and women (HR=2.43, 95% CI=1.52-3.90). Increased high-density lipoprotein was associated with a decreased risk in men (highest vs. lowest quarter HR=0.22, 95% CI=0.09-0.52) and women (HR=0.55, 95% CI=0.36-0.85). No effects were found for serum cholesterol and low-density lipoprotein. CONCLUSION: Obesity and alcohol influence gallstone formation, possibly in part through their effects on serum lipids. Reducing obesity may prevent gallstones in the population, as 38% of incident cases of gallstones were associated with a BMI of more than 25.

Physical activity reduces the risk of symptomatic gallstones: a prospective cohort study.

BACKGROUND AND AIMS: Physical activity may prevent gallstones formation by reducing bile stasis and plasma triglycerides and elevating high-density lipoprotein cholesterol levels. This prospective study investigated the relationship of physical activity and symptomatic gallstones in both sexes, using a questionnaire validated against physiological measurements. METHODS: A total of 25 639 volunteers, aged 40-74 years, were recruited into the European Prospective Investigation of Cancer, Norfolk and completed a questionnaire recording occupational and recreational physical activity. This questionnaire was validated earlier against measures of energy expenditure and cardio-respiratory fitness. Participants were ranked into four groups of physical activity. The cohort was monitored over 14 years for symptomatic gallstones. The primary outcome was hazard ratios (HR) of developing gallstones at 5 years, calculated using Cox regression modelling. HRs were adjusted for body mass index, alcohol, hormone replacement therapy and parity. Further analysis of a binary variable compared the highest level of physical activity against a combination of the lowest three levels. RESULTS: After 5 years of follow-up, 135 participants (69.6% women) developed symptomatic gallstones. Comparing the highest level of physical activity against the lowest three levels, the multivariable analysis at 5 years was HR=0.30 (95% confidence interval=0.14-0.64, P=0.002). After 14 years the findings were attenuated (HR=0.70, 95% confidence interval=0.49-1.01, P=0.055). CONCLUSION: The highest level of physical activity was associated with a 70% decreased risk of symptomatic gallstones after 5 years. This association may be causal as there are consistent experimental and epidemiological data for a protective effect. Physical activity should be accurately measured in studies investigating gallstones aetiology.