In this issue of Epidemiology, De Roos and her colleagues1 present a study of nitrates in public drinking water and the associated risk of colon and rectal cancer. The authors found no appreciable main effects, although there were plausible interactions in the presence of low dietary vitamin C and high meat consumption. De Roos and her colleagues carried out a careful study within the constraints of a retrospective design. However, is “as good as possible” good enough?
Waterborne exposures are notoriously difficult to assess retrospectively. In this study, the average nitrate in public drinking water was a surrogate for individual consumption of nitrates from all water sources. Nitrate data for drinking water before 1960 was not considered. Nitrate intake from well water was likewise omitted, even though study participants had used well water for an average of 14 years. Nitrates were used as a surrogate for nitrosamine formation in the gut, a process that varies greatly from person to person. Dietary intake of nitrates could dwarf the intake from water, and dietary assessment has its own well-known limitations.
All of these problems are likely to result in considerable exposure measurement error. The confidence intervals for the odds ratios in this study reflect only random error. They would presumably be much wider if they also included the uncertainty resulting from measurement error.2
Such problems are not unique to this study. The investigation of health effects associated with water pollutants suffers the classic problems of all research on environmental factors and endemic disease.3 Exposures are typically low, fairly homogeneous, and hard to measure retrospectively. Furthermore, true biologic effects are likely to be small, so that even the observed associations leave worries about possible confounding. Recent studies have greatly improved on the old ecologic studies by collecting historical data on water quality from public water supplies and individual-level data on past levels of water intake. Still, we could be approaching the limit of what we can learn from retrospective designs.
What are the alternatives? Prospective studies can combine careful exposure measurements with short-term markers for future disease. Some examples of possible intermediate end points are nitrosamine formation resulting from nitrates and premalignant changes in bladder cells that are shed in urine. Long-term follow up for cancer or other diseases would be more definitive but very expensive. Even so, they might be worth considering given the potential public health burden of the common water pollutants.
What are the major water pollutants of concern? De Roos et al.1 studied nitrates, which come from manufactured fertilizers. Although we know nitrates can form carcinogenic nitrosamines in the gut, the epidemiologic links between water nitrates and digestive cancers are in fact weak. Other worrisome water pollutants are disinfectant byproducts, arsenic and microbes. Recently, there has also been concern about the trace pharmaceuticals and personal care products that show up in our water supplies.4
The oldest waterborne problem of all is microbes. In the United States, an estimated 75% of drinking water is treated with chlorine to kill microbes. Unfortunately, chlorination does not eliminate the endemic gastrointestinal diseases carried by water. A range of creative research strategies have been used to assess the extent of this problem, including intervention studies,5 time-series analyses,6 and sero-epidemiology studies.7 These studies suggest persistent illness even from the low levels of microbes in conventionally treated surface water. There is also concern about posttreatment contamination in the water distribution system.8 Deficiencies in the distribution system have been implicated in up to 30% of recent waterborne disease outbreaks.9,10 Curiously, the role of distribution systems in endemic illness has yet to be addressed by epidemiologic studies.
Although chlorination has been successful in at least reducing microbial infection, this success has come at the cost of introducing low levels of trihalomethane into the water system. The principal concern is cancer,11 although there could also be an increase in reproductive problems.12,13 Although the increase in bladder cancer risk attributed to trihalomethane exposure is small, the public health burden could be large. By current U.S. Environmental Protection Agency (EPA) estimates, the attributable risk is 2% to 17% for the 54,000 new cases of bladder cancer diagnosed in the United States each year.14
The EPA is considering a reduction in the current standard of 80 parts per billion (ppb) for total trihalomethane, which would require a reduction in the use of chlorine. The dilemma is that some alternatives to chlorination are not as effective in reducing the concentration of microbes, and these alternatives can create other carcinogens that are less well studied than trihalomethane.15
Arsenic is another common water contaminant worldwide. Arsenic in drinking water increases the risk of bladder and lung cancer, although at levels higher than those in U.S. drinking water.16 Although the cancer risk at lower levels of arsenic is not clear, the U.S. EPA’s decision to lower the arsenic standard from 50 ppb to 10 ppb has been generally regarded as prudent.
Water resources are becoming more limited, and water supplies are used and reused more intensively. Questions about water quality will only grow in their public health importance. There is perhaps no other area of public health where the tradeoffs of alternative policies are more stark. The challenge to epidemiology is to inform these policy decisions. This will require appropriate new methods to improve exposure assessment and measurement of health outcomes as well as better quantification of the uncertainty of the results.
ABOUT THE AUTHOR
kyle steenland is a professor in the Department of Environment and Occupational Health at Emory University. He is coeditor of a text on environmental epidemiology. christine moe is an associate professor in the Departments of International Health, Epidemiology, and Environmental and Occupational Health, also at Emory. She serves on the Water Science and Technology Board of the National Research Council and the Research Advisory Council for the American Water Works Research Foundation, and has been a member of the USEPA Science Advisory Board for Drinking Water.
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