Tag Archives: epidemiology

Taiwan Arsenic Study of Limited Value

The confidence intervals on the data analysis presented here are very wide. A lower confidence interval of 1 indicates no effect. Studies such as this showing no association or a weak association are of very limited usefulness.

Hsu LI, Hsieh FI, Wang YH, Lai TS, Wu MM, Chen CJ, Chiou HY, Hsu KH. Arsenic Exposure From Drinking Water and the Incidence of CKD in Low to Moderate Exposed Areas of Taiwan: A 14-Year Prospective Study. Am J Kidney Dis. 2017 Aug 23. pii: S0272-6386(17)30800-4. doi: 10.1053/j.ajkd.2017.06.012.

BACKGROUND: Arsenic exposure is associated with decreased kidney function. The association between low to moderate arsenic exposure and kidney disease has not been fully clarified.

STUDY DESIGN: The association between arsenic exposure from drinking water and chronic kidney disease (CKD) was examined in a long-term prospective observational study.

SETTING & PARTICIPANTS: 6,093 participants 40 years and older were recruited from arseniasis-endemic areas in northeastern Taiwan. Arsenic levels were 28.0, 92.8, and 295.7μg/L at the 50th, 75th, and 90th percentiles, respectively.

PREDICTOR: Well-water arsenic and urinary total arsenic (inorganic plus methylated arsenic species) concentrations, adjusted for urinary creatinine concentration.

OUTCOMES: Kidney diseases (ICD-9 codes: 250.4, 274.1, 283.11, 403.*1, 404.*2, 404.*3, 440.1, 442.1, 447.3, or 580-589) and CKD (ICD-9 code: 585) ascertained using Taiwan’s National Health Insurance database 1998 to2011.

MEASUREMENTS: HRs contrasting CKD risk across arsenic exposure levels were estimated using Cox regression. Prevalence ORs for proteinuria (protein excretion ≥ 200mg/g) comparing quartiles of total urinary arsenic concentrations were estimated using logistic regression.

RESULTS: We identified 1,104 incident kidney disease cases, including 447 CKD cases (incidence rates, 166.5 and 67.4 per 104 person-years, respectively). A dose-dependent association between well-water arsenic concentrations and kidney diseases was observed after adjusting for age, sex, education, body mass index, cigarette smoking, alcohol consumption, and analgesic use. Using arsenic concentration ≤ 10.0μg/L as reference, multivariable-adjusted HRs for incident CKD were 1.12 (95% CI, 0.88-1.42), 1.33 (95% CI, 1.03-1.72), and 1.33 (95% CI, 1.00-1.77) for arsenic concentrations of 10.1 to 49.9, 50.0 to 149.9, and ≥150.0μg/L, respectively (P for trend=0.02). The association between arsenic concentration and kidney diseases was stronger for women (P for interaction=0.06). Arsenic values in the range of 50th to 75th and 75th to 100th percentiles of total urinary arsenic concentrations were associated with 50% and 67% higher prevalences, respectively, of proteinuria.

LIMITATIONS: Kidney diseases and CKD outcomes were based on diagnostic codes. Glomerular filtration rates were not available. Other heavy metals were not measured.

CONCLUSIONS: This study describes the temporal relationship between arsenic concentrations ≥ 10μg/L in drinking water and CKD. A dose-dependent association between well-water arsenic concentration and kidney diseases was observed. Higher creatinine-adjusted urinary total arsenic concentrations were associated with a higher prevalence of proteinuria.

Ohio Arsenic Study Exposure Assessment Inadequate, Inconclusive

Alarming as this study may appear, it is simply another in a long line of weak ecologic studies examining birth outcomes and drinking water that rely on an inadequate exposure assessment. The exposure was not directly measured and is unknown. In studies such as this statistical manipulations simply cannot reliably compensate for an inadequate assessment of contaminant exposure.

Almberg KS, Turyk ME, Jones RM, Rankin K, Freels S, Graber JM, Stayner LT. Arsenic in drinking water and adverse birth outcomes in Ohio. Environ Res. 2017 May 15;157:52-59. doi: 10.1016/j.envres.2017.05.010.

BACKGROUND: Arsenic in drinking water has been associated with adverse reproductive outcomes in areas with high levels of naturally occurring arsenic. Less is known about the reproductive effects of arsenic at lower levels.

OBJECTIVES: This research examined the association between low-level arsenic in drinking water and small for gestational age (SGA), term low birth weight (term LBW), very low birth weight (VLBW), preterm birth (PTB), and very preterm birth (VPTB) in the state of Ohio.

METHODS: Exposure was defined as the mean annual arsenic concentration in drinking water in each county in Ohio from 2006 to 2008 using Safe Drinking Water Information System data. Birth outcomes were ascertained from the birth certificate records of 428,804 births in Ohio from the same time period. Multivariable generalized estimating equation logistic regression models were used to assess the relationship between arsenic and each birth outcome separately. Sensitivity analyses were performed to examine the roles of private well use and prenatal care utilization in these associations.

RESULTS: Arsenic in drinking water was associated with increased odds of VLBW (AOR 1.14 per µg/L increase; 95% CI 1.04, 1.24) and PTB (AOR 1.10; 95% CI 1.06, 1.15) among singleton births in counties where <10% of the population used private wells. No significant association was observed between arsenic and SGA, or VPTB, but a suggestive association was observed between arsenic and term LBW.

CONCLUSIONS: Arsenic in drinking water was positively associated with VLBW and PTB in a population where nearly all (>99%) of the population was exposed under the current maximum contaminant level of 10µg/L. Current regulatory standards may not be protective against reproductive effects of prenatal exposure to arsenic.

Atrazine in Drinking Water Not Associated with Overian Cancer, Iowa

Inoue-Choi M, Weyer PJ, Jones RR, Booth BJ, Cantor KP, Robien K, Ward MH Atrazine in public water supplies and risk of ovarian cancer among postmenopausal women in the Iowa Women’s Health Study. Occupational and Environmental Medicine. 2016 Jul 1. pii: oemed-2016-103575. doi: 10.1136/oemed-2016-103575.

BACKGROUND: Few studies have evaluated environmental chemical exposures in relation to ovarian cancer. We previously found an increased risk of ovarian cancer among postmenopausal women in Iowa associated with higher nitrate levels in public water supplies (PWS). However, elevated nitrate levels may reflect the presence of other agricultural chemicals, such as atrazine, one of the most commonly detected pesticides in Iowa PWS.

METHODS: We evaluated the association between atrazine in drinking water and incident ovarian cancer (N=145, 1986-2010) among 13 041 postmenopausal women in the Iowa Women’s Health Study who used their PWS for ≥11 years as reported in 1989. Average levels of atrazine (1986-1987), nitrate-nitrogen (NO3-N, 1955-1988) and estimated levels of total trihalomethanes (TTHM, 1955-1988) from PWS monitoring data were linked to the participants’ cities of residence. We computed HRs and 95% CIs by categories of the average atrazine level (not detected, ≤ or >0.37 parts per billion=median) using Cox proportional hazards regression adjusting for ovarian cancer risk factors.

RESULTS: Atrazine was detected in water samples from 69 cities where 4155 women (32%) lived and levels were moderately correlated with NO3-N (ρ=0.35) and TTHM (ρ=0.24). Atrazine levels were not associated with ovarian cancer risk with or without adjusting for NO3-N and TTHM levels (p-trend=0.50 and 0.81, respectively). Further, there was no evidence for effect modification of the atrazine association by NO3-N or TTHM levels.

CONCLUSIONS: In our study with low atrazine detection rates, we found no association between atrazine in PWS and postmenopausal ovarian cancer risk.

Spain, Italy THM Exposure and Colorectal Cancer; No Association Found

Villanueva CM, Gracia-Lavedan E, Bosetti C, Righi E, Molina AJ, Martín V, Boldo E, Aragonés N, Perez-Gomez B, Pollan M, Gomez Acebo I, Altzibar JM, Jiménez Zabala A, Ardanaz E, Peiró R, Tardón A, Chirlaque MD, Tavani A, Polesel J, Serraino D, Pisa F, Castaño-Vinyals G, Espinosa A, Espejo-Herrera N, Palau M, Moreno V, La Vecchia C, Aggazzotti G, Nieuwenhuijsen MJ, Kogevinas M. Colorectal Cancer and Long-Term Exposure to Trihalomethanes in Drinking Water: A Multicenter Case-Control Study in Spain and Italy. Environmental Health Perspectives. 2016 Jul 6.

BACKGROUND: Evidence on the association between colorectal cancer and exposure to disinfection by-products in drinking water is inconsistent.

OBJECTIVES: We assessed long-term exposure to trihalomethanes (THMs), the most prevalent group of chlorination by-products, to evaluate the association with colorectal cancer.

METHODS: A multicentre case-control study was conducted in Spain and Italy in 2008-2013. Hospital-based incident cases, population-based (Spain) and hospital-based (Italy) controls were interviewed to ascertain residential histories, water type consumed in each residence, frequency and duration of showering/ bathing, and major recognized risk factors for colorectal cancer. We estimated adjusted odds ratios (OR) for colorectal cancer in association with quartiles of estimated average lifetime THM concentrations in each participant’s residential tap water (μg/L, from age 18 to two years before the interview) and estimated average lifetime THM ingestion from drinking residential tap water (μg/day).

RESULTS: Subjects analyzed were 2047 cases and 3718 controls. Median values (ranges) for average lifetime residential tap water concentrations of total THMs, chloroform, and brominated THMs were 30 (0-174), 17 (0-63), and 9 (0-145) μg/L, respectively. Total THM concentration in residential tap water was not associated with colorectal cancer (OR=0.92, 95%CI: 0.66-1.28 for highest vs. lowest quartile), but chloroform concentrations were inversely associated (OR=0.31, 95%CI: 0.24-0.41 for highest vs. lowest quartile). Brominated THMs concentrations showed a positive association among men at the highest vs. lowest quartile (OR=1.43, 95%CI: 0.83-2.46). Patterns of associations were similar for estimated average THM ingestion through residential water consumption.

CONCLUSIONS: We did not find clear evidence of an association between detailed estimates of lifetime total THM exposures and colorectal cancer in our large case-control study population. Negative associations with chloroform concentrations and ingestion suggest differences among specific THMs, but these findings need confirmation in other study populations.

Trihalomethanes Not Associated with Adverse Birth Outcomes, Spain

Cristina M. Villanueva, Esther Gracia-Lavedán, Jesús Ibarluzea, Loreto Santa Marina, Ferran Ballester, Sabrina Llop, Adonina Tardón, Mariana F. Fernández,  Carmen Freire, Fernando Goñi, Xavier Basagaña, Manolis Kogevinas, Joan O. Grimalt, and Jordi Sunyer, on behalf of the INMA (Infancia y Medio Ambiente) Project. Exposure to Trihalomethanes through Different Water Uses and Birth Weight, Small for Gestational Age, and Preterm Delivery in Spain  Volume 119, Number 12, December 2011

Background: Evidence associating exposure to water disinfection by-products with reduced birth weight and altered duration of gestation remains inconclusive.

Objective: We assessed exposure to trihalomethanes (THMs) during pregnancy through different water uses and evaluated the association with birth weight, small for gestational age (SGA), low birth weight (LBW), and preterm delivery.

Methods: Mother–child cohorts set up in five Spanish areas during the years 2000–2008 contributed data on water ingestion, showering, bathing, and swimming in pools. We ascertained residential THM levels during pregnancy periods through ad hoc sampling campaigns (828 measurements) and regulatory data (264 measurements), which were modeled and combined with personal water use and uptake factors to estimate personal uptake. We defined outcomes following standard definitions and included 2,158 newborns in the analysis.

Results: Median residential THM ranged from 5.9 μg/L (Valencia) to 114.7 μg/L (Sabadell), and speciation differed across areas. We estimated that 89% of residential chloroform and 96% of brominated THM uptakes were from showering/bathing. The estimated change of birth weight for a 10% increase in residential uptake was –0.45 g (95% confidence interval: –1.36, 0.45 g) for chloroform and 0.16 g (–1.38, 1.70 g) for brominated THMs. Overall, THMs were not associated with SGA, LBW, or preterm delivery.

Conclusions: Despite the high THM levels in some areas and the extensive exposure assessment, results suggest that residential THM exposure during pregnancy driven by inhalation and dermal contact routes is not associated with birth weight, SGA, LBW, or preterm delivery in Spain.

 

Drinking Water Nitrate and Colorectal Cancer Risk

Studies such as this are an enormous undertaking and authors are to be commended for their effort. Assessing actual exposure is typically the weakest component as personal interviews and after-the-fact surveys are known to be unreliable. Water system monitoring records are not intended to represent human exposure. This could sway the subtle associations reported here up or down. At best it can be concluded that additional study should be considered. But even if the associations reported here were much higher or much lower, such results could be misleading given the inherent limitations of the study design. This comment is not intended as a criticism of this work. But recognition of the realities associated with this type of epidemiological study. Learn what we can from it and then move on.

Espejo-Herrera N, Gràcia-Lavedan E, Boldo E, Aragonés N, Pérez-Gómez B, Pollán M, Molina AJ, Fernández T, Martín V, La Vecchia C, Bosetti C, Tavani A, Polesel J, Serraino D, Gómez Acebo I, Altzibar JM, Ardanaz E, Burgui R, Pisa F, Fernández-Tardón G, Tardón A, Peiró R, Navarro C, Castaño-Vinyals G, Moreno V, Righi E, Aggazzotti G, Basagaña X, Nieuwenhuijsen M, Kogevinas M, Villanueva CM. Colorectal cancer risk and nitrate exposure through drinking water and diet. International Journal of Cancer. 2016 Mar 8. doi: 10.1002/ijc.30083.

Ingested nitrate leads to the endogenous synthesis of N-nitroso compounds (NOCs), animal carcinogens with limited human evidence. We aimed to evaluate the risk of colorectal cancer (CRC) associated with nitrate exposure in drinking water and diet. We conducted a case-control study in Spain and Italy during 2008-2013. Hospital-based incident cases and population-based (Spain) or hospital-based (Italy) controls were interviewed on residential history, water consumption since age 18, and dietary information. Long-term waterborne ingested nitrate was derived from routine monitoring records, linked to subjectś residential histories and water consumption habits. Dietary nitrate intake was estimated from food frequency questionnaires and published food composition databases. Odd ratios (OR) were calculated using mixed models with area as random effect, adjusted for CRC risk factors, and other covariables. Generalized additive models (GAMs) were used to analyze exposure-response relationships. Interaction with endogenous nitrosation factors and other covariables was also evaluated. We analyzed 1869 cases and 3530 controls. Average waterborne ingested nitrate ranged from 3.4 to 19.7 mg/day, among areas. OR (95% CIs) of CRC was 1.49 (1.24, 1.78) for >10 vs. ≤5 mg/day, overall. Associations were larger among men vs. women, and among subjects with high red meat intake. GAMs showed increasing exposure-response relationship among men. Animal-derived dietary nitrate was associated with rectal, but not with colon cancer risk. In conclusion, a positive association between CRC risk and waterborne ingested nitrate is suggested, mainly among subgroups with other risk factors. Heterogeneous effects of nitrate from different sources (water, animal and vegetables) warrant further research.

No Increased Lung Cancer Risk at ~100 to 150 ug/L Arsenic

No one wants arsenic in their drinking water. But continued effort to push the health goal for arsenic lower and lower in the absence of evidence of harm is counter productive.

Lamm SH, Ferdosi H, Dissen EK, Li J, Ahn J. A Systematic Review and Meta-Regression Analysis of Lung Cancer Risk and Inorganic Arsenic in Drinking Water. Int J Environ Res Public Health. 2015 Dec 7;12(12):15498-515. doi: 10.3390/ijerph121214990.

High levels (> 200 µg/L) of inorganic arsenic in drinking water are known to be a cause of human lung cancer, but the evidence at lower levels is uncertain. We have sought the epidemiological studies that have examined the dose-response relationship between arsenic levels in drinking water and the risk of lung cancer over a range that includes both high and low levels of arsenic. Regression analysis, based on six studies identified from an electronic search, examined the relationship between the log of the relative risk and the log of the arsenic exposure over a range of 1-1000 µg/L. The best-fitting continuous meta-regression model was sought and found to be a no-constant linear-quadratic analysis where both the risk and the exposure had been logarithmically transformed. This yielded both a statistically significant positive coefficient for the quadratic term and a statistically significant negative coefficient for the linear term. Sub-analyses by study design yielded results that were similar for both ecological studies and non-ecological studies. Statistically significant X-intercepts consistently found no increased level of risk at approximately 100-150 µg/L arsenic.