Prospective evaluation of dietary intake of essential metals and pancreatic cancer risk: The Multiethnic Cohort Study

Background : Evidence suggests that dietary intake levels of essential metals are linked to the development of or protection against pancreatic adenocarcinoma (PDAC). However, results from existing epidemiological studies remain inconsistent, often limited by retrospective designs and recall bias. We aim to prospectively investigate the relationship between dietary intake of essential metals and the risk of PDAC in a large, racially and ethnically diverse U.S. population. Methods : Data were from the Multiethnic Cohort Study, a large population-based prospective cohort study established between 1993 and 1996 in Los Angeles and Hawaii, comprised of participants from five main racial and ethnic groups (African American, Japanese American, Latino, Native Hawaiian, and White). Incident PDAC cases were identified through linkage with the state SEER cancer registries. Dietary intake densities (intake per 1,000 kcal per day) of seven essential metals (copper, selenium, zinc, manganese, iron, calcium, and magnesium) were estimated from a baseline quantitative food frequency questionnaire and modeled as quartiles. Participants were excluded if they were of other racial/ethnic groups, had implausible dietary data, a prior diagnosis of PDAC, or inconsistent/incomplete follow-up time. Cox proportional hazards regression models (with age since cohort entry as time metric) were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for PDAC risk associated with intake of each essential metal , adjusting for age, sex, race/ethnicity, body mass index, history of diabetes, alcohol use, smoking status, education, family history of PDAC, and total daily energy intake. Results : After an average follow-up of 20.2 years, 2,119 of 195,061 at-risk participants developed PDAC. Compared with the lowest quartile (5.7 - 44.9 mcg/1,000 kcal/day), participants in the highest quartile (58.0 - 131.9 mcg/1,000 kcal/day) of selenium intake had a 17% higher risk of developing PDAC (HR=1.17, 95% CI: 1.03-1.34, P-trend=0.048). No evidence of heterogeneity across sex and race/ethnicity was observed (all P's-heterogeneity>0.05); however associations appeared stronger for White (HR=1.27, 95% CI: 0.95-1.70), African American (HR=1.29, 95% CI: 0.96-1.73) and Latino (HR=1.32, 95% CI: 0.96-1.80) participants. No significant associations were observed for dietary intakes of copper, zinc, manganese, iron, calcium, and magnesium. Conclusion : Elevated selenium dietary intake is associated with an increased risk of PDAC in this large, racially and ethnically diverse U.S. population. Further large-scale prospective studies are warranted to confirm this association and elucidate the underlying biological mechanisms .