Arsenic exposure and cancer mortality in a US-based prospective cohort: The strong heart study

Background: Inorganic arsenic, a carcinogen at high exposure levels, is a major global health problem. rospective studies on carcinogenic effects at low-moderate arsenic levels are lacking. Methods: We evaluated the association between baseline arsenic exposure and cancer mortality in 3,932 American Indians, 45 to 74 years of age, from Arizona, Oklahoma, and North/South Dakota who participated in the Strong Heart Study from 1989 to 1991 and were followed through 2008. We estimated inorganic arsenic exposure as the sum of inorganic and methylated species in urine. Cancer deaths (386 overall, 78 lung, 34 liver, 18 prostate, 26 kidney, 24 esophagus/stomach, 25 pancreas, 32 colon/rectal, 26 breast, and 40 lymphatic/ hematopoietic) were assessed by mortality surveillance reviews. We hypothesized an association with lung, liver, prostate, and kidney cancers. Results: Median (interquartile range) urine concentration for inorganic plus methylated arsenic species was 9.7 (5.8-15.6) μg/g creatinine. The adjusted HRs [95% confidence interval (CI)] comparing the 80th versus 20th percentiles of arsenic were 1.14 (0.92-1.41) for overall cancer, 1.56 (1.02-2.39) for lung cancer, 1.34 (0.66, 2.72) for liver cancer, 3.30 (1.28-8.48) for prostate cancer, and 0.44 (0.14, 1.14) for kidney cancer. The corresponding hazard ratios were 2.46 (1.09-5.58) for pancreatic cancer, and 0.46 (0.22-0.96) for lymphatic and hematopoietic cancers. Arsenic was not associated with cancers of the esophagus and stomach, colon and rectum, and breast. Conclusions: Low to moderate exposure to inorganic arsenic was prospectively associated with increased mortality for cancers of the lung, prostate, and pancreas. Impact: These findings support the role of low-moderate arsenic exposure in development of lung, prostate, and pancreas cancer and can inform arsenic risk assessment.