Ingested nitrate and nitrite, disinfection by-products, and pancreatic cancer risk in postmenopausal women

Nitrate and nitrite are precursors of N-nitroso compounds (NOC), probable human carcinogens that cause pancreatic tumors in animals. Disinfection by-products (DBP) exposures have also been linked with digestive system cancers, but few studies have evaluated relationships with pancreatic cancer. We investigated the association of pancreatic cancer with these drinking water contaminants and dietary nitrate/nitrite in a cohort of postmenopausal women in Iowa (1986-2011). We used historical monitoring and treatment data to estimate levels of long-term average nitrate and total trihalomethanes (TTHM; the sum of the most prevalent DBP class) and the duration exceeding one-half the maximum contaminant level (>1/2 MCL; 5 mg/L nitrate-nitrogen, 40 mu g/L TTHM) among participants on public water supplies (PWS) >10 years. We estimated dietary nitrate and nitrite intakes using a food frequency questionnaire. We computed hazard ratios (HR) and 95% confidence intervals (CI) using Cox regression and evaluated nitrate interactions with smoking and vitamin C intake. We identified 313 cases among 34,242 women, including 152 with >10 years PWS use (N=15,710). Multivariable models of average nitrate showed no association with pancreatic cancer (HRp95 (vs. Q1)=1.16, 95% CI: 0.51-2.64). Associations with average TTHM levels were also null (HRQ4 (vs. Q1)=0.70, 95% CI:0.42-1.18). We observed no trend with increasing years of exposure to either contaminant at levels >1/2 MCL. Positive associations were suggested in the highest dietary nitrite intake from processed meat (HRp95 (vs. Q1)=1.66, 95% CI 1.00-2.75;p(trend)=0.05). We found no interactions of nitrate with known modifiers of endogenous NOC formation. Our results suggest that nitrite intake from processed meat may be a risk factor for pancreatic cancer.