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Nitrates and Prostate Cancer: Long-Term Drinking Water Exposures Associated with Risk of Tumors

2023; National Institute of Environmental Health Sciences; Volume: 131; Issue: 5 Linguagem: Inglês

10.1289/ehp12925

1552-9924

Silke Schmidt,

Sulfur Compounds in Biology

Vol. 131, No. 5 Science SelectionOpen AccessNitrates and Prostate Cancer: Long-Term Drinking Water Exposures Associated with Risk of Tumorsis accompanied byLong-Term Exposure to Nitrate and Trihalomethanes in Drinking Water and Prostate Cancer: A Multicase–Control Study in Spain (MCC-Spain) Silke Schmidt Silke Schmidt Search for more papers by this author Published:25 May 2023CID: 054003https://doi.org/10.1289/EHP12925AboutSectionsPDF ToolsDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InReddit AbstractProstate cancer is the second-most common cancer in men, with more than 1.4 million new diagnoses worldwide in 2020.1 Its environmental risk factors include exposures to pesticides2; endocrine-disrupting chemicals, such as bisphenol A and polychlorinated biphenyls3; and nitrate and nitrites.4 Nitrate and nitrite additives in processed meat can form carcinogenic nitrosamines in the human body in a process called endogenous nitrosation.5 Drinking water may also be a source of exposure to nitrate6; it can also contain disinfection by-products (DBPs) formed when chlorine, the world’s most widely used drinking water disinfectant,7 reacts with naturally occurring organic material.8 Nitrate contamination of water has been rising for years in most developed countries owing to intensive irrigation, livestock farming, and use of synthetic nitrogen-based fertilizers.9 Although these activities have also increased nitrate levels in plant-based foods, beneficial components in fruits and vegetables protect against endogenous nitrosation.10Previous studies4,11 prompted researchers in Spain to examine associations between waterborne nitrate and prostate cancer in a large case–control study recently published in Environmental Health Perspectives.7 The team analyzed 697 hospital-based incident prostate cancer cases and 927 population-based controls recruited in Spain from 2008 to 2013.12 Self-reported residential address histories (since the age of 18 years) were combined with amounts and sources (municipal, bottled, or private wells) of consumed water to estimate ingested levels of nitrate, along with certain DBPs.The highest levels of exposures to nitrates in municipal and bottled drinking water were associated higher risk of prostate cancer—especially the more aggressive form. However, associations with trihalomethane disinfection by-products, although not significant, suggested that dermal and inhalation might be more important exposure routes than ingestion. Image © Drazen/stock.Adobe.com.For municipal water, nitrate and DBP data were provided by public and private water utilities. For bottled water, the authors measured nitrate in the 9 most-consumed brands, and they used previously reported average DBP levels in 15 popular brands.13 Private wells had limited data but were used by only 2% of participants, compared with 78% for municipal water and 20% for bottled water.The team found that people whose estimated ingested nitrate exposures were in the top third (above 13.8 milligrams per day13.8mg/day) experienced a 1.7-fold increased risk of prostate cancer compared with those whose exposures were in the bottom third (below 5.5 milligrams per day5.5mg/day). Most of these higher levels were well below the World Health Organization’s guideline of 50 milligrams per day50mg/L.14 Notably, the nitrate association was stronger for aggressive prostate cancer than for the less aggressive form. Additional analyses showed that the nitrate–prostate cancer association was also stronger in men with low reported intakes of fiber, fruits, vegetables, and vitamin C. Nutrient intakes were calculated from food consumption using standard Spanish food composition tables.15Bernard Srour, an epidemiologist at the French National Institute of Health and Medical Research, points to the built-in protection that dietary fiber, fruits, and vegetables offer against nitrate’s potential harm.16,17 “The study suggests that the association between nitrate and prostate cancer was weaker in participants consuming high amounts of fiber, fruits, and vegetables, which contain antioxidants, polyphenols, and vitamins as protective agents,” says Srour, who was not involved in the study. “It would be interesting to test in experimental studies whether cancer risks differ for nitrate in produce versus food additives [such as flavorings and preservatives].”For the DBP evaluation, the researchers focused on chloroform and three brominated trihalomethanes (THMs), which are among the most abundant DBPs formed.18 No significant associations were observed between exposures to these chemicals and prostate cancer, but the findings suggested a potential association with residential tap water levels, rather than ingested water itself. This implies that inhalation and dermal absorption may be the more pertinent exposure routes for these chemicals.“Unlike nitrate, THMs are volatile and skin-permeable gaseous chemicals that may be inhaled or absorbed through the skin when people shower, bathe, or wash dishes, in addition to being ingested,” says Carolina Donat-Vargas, the study’s first author and a researcher at ISGlobal in Barcelona and the Karolinska Institutet in Stockholm. “The relative importance of these three exposure routes likely varies across DBP subtypes.”Laura Beane Freeman, an epidemiologist at the U.S. National Cancer Institute (NCI) who was not involved in the project, agrees that dermal or inhalation exposure to THMs may be more relevant than ingestion for prostate cancer. “These exposure routes have also been implicated in studies of bladder cancer,” she says.Mary Ward, also an epidemiologist at the NCI who was not involved in the study, applauds the study’s sample size and careful design. “The ability to evaluate long-term average exposures and [analyze] aggressive prostate cancer separately from nonaggressive cancer is a major strength,” says Ward. “Nitrate ingestion under conditions that result in endogenous nitrosation may be the underlying mechanism for the increase in prostate cancer incidence observed in this study.”Silke Schmidt, PhD, writes about science, health, and the environment from Madison, Wisconsin.References1. 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