— July 22, 2026 · Tap-Water Disinfection Byproducts and Uterine Cancer: A 53,100-Woman California Cohort

Table of Contents

1. The Study at a Glance
2. What Was Done
3. What Disinfection Byproducts Are
4. What Was Found, Number by Number
5. How It Might Work
6. How It Fits With Earlier Research
7. What It Cannot Show
8. What the Researchers and the Commentary Said
9. What Remains Unknown
10. Sources and Primary Documents
11. Key Research Papers
12. Connections

The Study at a Glance

• Paper — “Drinking Water Contaminant Exposures and Risk of Uterine Cancer”, JAMA Network Open 9(7):e2624391, published online July 22, 2026 (the issue is dated July 1, which is the date PubMed shows).
• Who — 13 researchers, most from the Occupational and Environmental Epidemiology Branch of the US National Cancer Institute, with colleagues from Columbia University, the City of Hope research institute and California’s Office of Environmental Health Hazard Assessment.
• Design — prospective cohort: women were enrolled in 1995–1996, before any diagnosis, and followed through December 31, 2020.
• Size — 53,100 women (median age 50 at enrolment), 1,038 uterine cancers diagnosed during follow-up: 864 endometrioid and 154 nonendometrioid tumours.
• Exposure — the 15-year average (1990–2005) level of each contaminant in the community water system serving the home address; haloacetic acids averaged over 1990–2013.
• Main result — top third vs bottom third of total trihalomethanes: hazard ratio 1.18 (1.02–1.38) for uterine cancer overall and 1.23 (1.05–1.46) for endometrioid tumours.
• No association — nitrate, arsenic and uranium.
• Funding — the US National Cancer Institute; the paper states the funders had no role in the analysis or the decision to publish.

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What Was Done

The California Teachers Study began in 1995–1996, when 133,476 public-school teachers and administrators in the state’s teachers’ retirement system returned a mailed questionnaire. It was set up to study the causes of breast cancer and other cancers. New cancers among its members are identified through the California Cancer Registry, and deaths through state and national death records.

For this analysis the researchers first set aside 23,635 women who had already had a hysterectomy, 13,603 who already had cancer, and 8,332 who lived outside California. That left 87,881 eligible women. Of these, 81,093 (92%) had a home address inside the service boundary of one of 1,127 community water systems. The 6,788 whose address did not fall inside any public system were assumed to use private wells and were left out, because private wells are not regulated or routinely tested.

To make sure the water records described water the women had actually been living with, the main analysis kept only women who had lived at their enrolment address for 10 years or more. After removing 25,166 women with shorter stays and 2,827 whose water system had no trihalomethane records, the final group was 53,100 women, served by 913 water systems and followed for a combined 1,032,131 person-years.

The researchers obtained water-quality monitoring data for 1990–2020 from California’s Office of Environmental Health Hazard Assessment and calculated, for each water system, the average level of each contaminant from 1990 to 2005. They studied:

• Four trihalomethanes: chloroform, bromodichloromethane, dibromochloromethane and bromoform, which are regulated together as “total trihalomethanes”.
• Five haloacetic acids: monochloroacetic, dichloroacetic, trichloroacetic, monobromoacetic and dibromoacetic acid, regulated together as “HAA5”.
• Three inorganic contaminants: nitrate, arsenic and uranium.

Haloacetic acid records were sparse before 2013: location-based annual monitoring was in effect for every system only by October 1, 2013, under the federal Stage 2 rule. For these chemicals the averages ran from 1990 to 2013, and follow-up started on January 1, 2010, giving a shorter window (a mean of 9.3 years).

The statistical method, Cox regression, compared the rate of new uterine cancer diagnoses between women in the top, middle and bottom thirds of each exposure, after allowing for age, body weight (body mass index) and smoking. A second method, quantile-based g-computation, estimated the combined effect of the whole mixture of contaminants at once. The authors tested each result at the conventional 5% significance level without adjusting for the number of comparisons made.

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What Disinfection Byproducts Are

Public water is disinfected to kill the germs that cause waterborne illness. The US Environmental Protection Agency names Giardia, Cryptosporidium and viruses among them. The disinfectant itself, however, reacts with other material in the water. In the EPA’s words, “disinfectants can react with naturally-occurring materials in the water to form byproducts including: Trihalomethanes (THM), Haloacetic acids (HAA), Chlorite, and Bromate.”

Trihalomethanes and haloacetic acids are the two families regulated as groups. Their names describe their chemistry: each carries chlorine or bromine atoms. Chloroform had the highest median level of the four trihalomethanes in this cohort (2.79 µg/L); the “bromo” compounds contain bromine. The paper notes that people are exposed not only by drinking water but also by breathing in and absorbing these chemicals through the skin, “especially during showering or bathing.”

The EPA’s National Primary Drinking Water Regulations set these legal limits (maximum contaminant levels):

• Total trihalomethanes: 0.080 mg/L (80 µg/L). Listed health effects of long-term exposure above the limit: “Liver, kidney or central nervous system problems; increased risk of cancer.”
• Five haloacetic acids (HAA5): 0.060 mg/L (60 µg/L). Listed health effect: “Increased risk of cancer.”
• The groups have no combined health goal, but some members do: the EPA sets a goal of zero for bromodichloromethane, bromoform and dichloroacetic acid, 0.07 mg/L for chloroform and for monochloroacetic acid, 0.06 mg/L for dibromochloromethane and 0.02 mg/L for trichloroacetic acid.
• For comparison, the EPA limits are 0.010 mg/L for arsenic, 10 mg/L for nitrate (as nitrogen) and 30 µg/L for uranium.

Among the Federal Register notices the EPA lists for these byproducts are a final rule on trihalomethanes (November 29, 1979), the Stage 1 disinfection byproducts rule (December 16, 1998) and the Stage 2 rule (January 2, 2006). According to the paper, the International Agency for Research on Cancer has classified chloroform, bromodichloromethane, dibromoacetic acid and trichloroacetic acid as “possibly carcinogenic to humans” (Group 2B), based on insufficient evidence in human studies and sufficient evidence in laboratory animals.

In this cohort most levels were far below the federal limits, though the highest were above them. The median average was 4.56 µg/L for total trihalomethanes and 7.97 µg/L for the five haloacetic acids; the 95th percentile was 38.3 µg/L and 30.0 µg/L respectively; the highest values were 108.66 µg/L and 115.18 µg/L.

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What Was Found, Number by Number

A hazard ratio compares the rate of new diagnoses in a more exposed group with the rate in the least exposed group. A value of 1.00 means no difference; a value above 1.00 means a higher rate. The 95% confidence interval shows the range of values compatible with the data: when it includes 1.00, the result is compatible with no difference.

Total trihalomethanes

• The bottom third of women had water averaging 0 to 1.22 µg/L; the middle third 1.23 to 15.57 µg/L; the top third 15.58 to 108.66 µg/L.
• Uterine cancer overall: middle third 1.11 (0.96–1.30); top third 1.18 (1.02–1.38); test for trend P = .06.
• Endometrioid tumours: middle third 1.09 (0.92–1.29); top third 1.23 (1.05–1.46); trend P = .01.
• Nonendometrioid tumours: middle third 1.19 (0.81–1.74); top third 0.95 (0.63–1.42); trend P = .50 — no association.
• Each doubling of the total trihalomethane level: hazard ratio 1.02 (1.00–1.04) for uterine cancer overall.

The individual trihalomethanes

• Chloroform (top third 5.78–82.55 µg/L): hazard ratio 1.18 for uterine cancer overall (trend P = .07) and 1.27 (1.07–1.50) for endometrioid tumours (trend P = .01).
• Bromodichloromethane: endometrioid tumours 1.22 (1.03–1.44) in both the middle and top thirds (trend P = .11).
• Dibromochloromethane: endometrioid tumours, top third 1.16 (0.98–1.37).
• Bromoform: uterine cancer overall, top third 1.00 (0.87–1.16) — no association.

Haloacetic acids (follow-up from 2010)

• HAA5 (top third 13.11–115.18 µg/L): uterine cancer overall 1.18 (0.91–1.53), trend P = .21; endometrioid 0.99 (0.73–1.35); nonendometrioid 1.86 (1.06–3.25), trend P = .01, based on 35 cases in the top third.
• Monochloroacetic acid: nonendometrioid tumours, top third 1.86 (1.01–3.44), trend P = .05.
• Monobromoacetic acid, per doubling: uterine cancer overall 1.19 (1.05–1.34); endometrioid 1.21 (1.06–1.39).

Nitrate, arsenic and uranium

• Top third vs bottom third, uterine cancer overall: arsenic 0.95 (0.83–1.10); uranium 0.94 (0.80–1.09); nitrate 0.95 (0.81–1.10). In the authors’ words, “No associations were observed with 15-year mean arsenic, nitrate-N, or uranium exposures.”

The mixture

• For the combined mixture of the four trihalomethanes plus nitrate, arsenic and uranium, the hazard ratio per interquartile-range increase was 1.21 (0.96–1.53) for uterine cancer overall and 1.34 (1.04–1.74) for endometrioid tumours.
• Chloroform and dibromochloromethane contributed most to the mixture result for uterine cancer and endometrioid tumours.
• With each contaminant adjusted for all the others, total trihalomethanes had the highest hazard ratios: 1.13 (0.99–1.29) for uterine cancer overall and 1.18 (1.02–1.37) for endometrioid tumours.

Checks the authors ran

• Adding menopausal status, oral contraceptive use and births to the model “did not appreciably change risk estimates.”
• Restricting the analysis to the 49,394 women whose 15-year averages were below every federal limit gave consistent findings.
• Exposures that changed over time as women moved, lagged by 5 or 10 years, gave similar patterns with slightly weaker estimates; starting follow-up in 2005 gave similar patterns with higher hazard ratios.
• Results did not differ clearly by menopausal status, smoking or hormone therapy use. The highest chloroform hazard ratios were in women with a body mass index under 25.

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How It Might Work

The paper does not test a mechanism; it reports an association. In its discussion the authors cite laboratory studies that make a link biologically plausible:

• In experimental studies, certain trihalomethanes and haloacetic acids bind to estrogen receptors and have endocrine-disrupting properties that can cause hormonal dysregulation, which the paper calls “a hypothesized mechanism for uterine cancer development.”
• The bromine-containing trihalomethanes (but not chloroform) can damage DNA in cells when they are activated by an enzyme called glutathione S-transferase theta 1.
• Chloroform, the authors write, is likely to cause cancer through cell damage (cytotoxicity) rather than by damaging DNA directly (genotoxicity).
• Monobromoacetic and monochloroacetic acid caused oxidative stress and DNA damage in human cells in the laboratory; dichloroacetic and trichloroacetic acid reduced estrogen receptor levels in mice.

These are findings in cells and animals. Whether the same processes happen in women at the levels found in tap water is not known.

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How It Fits With Earlier Research

Uterine cancer. According to the paper, only one earlier study had looked at disinfection byproducts and this cancer: the Iowa Women’s Health Study, a cohort of postmenopausal women. Among 10,501 women who had used their public water supply for more than 10 years, those at the 95th percentile of exposure (total trihalomethanes 93 µg/L or more) had a higher rate of endometrial cancer than those in the lowest quarter: hazard ratio 2.19 (1.41–3.40) for total trihalomethanes and 1.84 (1.19–2.83) for haloacetic acids. As in California, nitrate showed no association. Exposures in California were lower at the top end: the 95th percentile of total trihalomethanes was 38.3 µg/L in California and 93.2 µg/L in Iowa. The authors describe their findings as “generally consistent” with Iowa’s.

Bladder cancer has the largest body of evidence. A 2003 meta-analysis of six case-control studies and two cohorts found that long-term (more than 40 years) consumption of chlorinated drinking water was associated with an odds ratio of 1.4 (1.2–1.7). A 2004 pooled analysis of 2,806 cases and 5,254 controls from the United States, Canada, France, Italy and Finland found that in men the odds ratio rose with exposure, to 1.44 (1.20–1.73) above 50 µg/L of trihalomethanes, but found no association in women (0.95; 0.76–1.20). A 2011 pooled analysis of European studies found a similar result in men above 50 µg/L compared with 5 µg/L or less (1.47; 1.05–2.05) and again none in women.

Routes other than drinking. A 2007 Spanish study of 1,219 cases linked bladder cancer to the length of showers and baths weighted by household trihalomethane level (top vs bottom quarter, 1.83; 1.17–2.87) and to swimming in pools (1.57; 1.18–2.09). A 2017 New England study of 1,213 cases found an association with the highest daily trihalomethane intake from drinking (1.53; 1.01–2.32), stronger for the brominated compounds (1.98; 1.19–3.29), and none with swimming-pool use.

Colorectal cancer: a 2010 meta-analysis of 13 studies found pooled relative risks of 1.27 (1.08–1.50) for colon and 1.30 (1.06–1.59) for rectal cancer, but the three cohort studies alone showed no clear association, and the authors concluded the evidence was “limited” and that study limitations “prevent causal inference.”

Burden estimates. A 2020 study of trihalomethane levels in 26 European Union countries estimated that, “assuming a causal association”, 4.9% of bladder cancers there (95% CI 2.5–7.1%), about 6,561 cases a year, could be attributed to trihalomethanes in drinking water.

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What It Cannot Show

• It cannot show cause and effect. It is an observational study. Women with more byproducts in their water may differ in other ways the analysis did not capture; the authors write that “residual confounding may still exist.”
• Exposure was assigned by address, not measured. Every woman served by the same water system received the same average value. The commentary refers to “the persistent ecological gap in this literature”: exposure estimated for whole service areas rather than measured in each person. An earlier study of this cohort found that at follow-up in 2017–2019 about 74% of women reported municipal tap water as their source and 15% bottled water.
• No data on how much water each woman drank, or how long she spent in the shower or bath.
• No water data before 1990, so exposures in childhood or earlier adulthood, and possible longer delays between exposure and cancer, could not be studied.
• The haloacetic acid results rest on thin data: records were sparse before 2013, follow-up for these chemicals began in 2010, and the nonendometrioid finding came from 35 cases in the top third.
• Many comparisons, no correction. The authors tested many chemicals, tumour types and cut-points without adjusting for multiple comparisons, which raises the chance that some individual results arose by chance. Several confidence intervals sit just above 1.00, and the overall trend for total trihalomethanes (P = .06) did not reach the conventional threshold.
• A particular population. Almost all participants had a college education, 85% were White and few lived in low-income neighbourhoods. The authors note that generalising to other populations “may be limited.”
• Private wells were excluded: about 8% of eligible women likely used wells, which are not regulated or routinely tested.

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What the Researchers and the Commentary Said

The authors’ Key Points summary states: “These findings suggest that long-term exposure to certain disinfection byproducts may increase the risk of uterine cancer.” Their conclusion describes “novel associations between THM exposures in drinking water and the risk of uterine cancer, particularly endometrioid histotypes,” and says the haloacetic acid findings call for caution “considering the limited number of historical estimates of these exposures.” They call drinking-water contaminants “potentially modifiable” and conclude that further research is warranted.

The journal published an invited commentary alongside the paper, by Shady Abohashem of Massachusetts General Hospital and Harvard Medical School, titled “Drinking Water Disinfection Byproducts and Uterine Cancer—A Modifiable Environmental Exposure Hiding in Plain Sight.” He wrote that “by replicating and extending the only prior cohort signal in a different exposure context, with a thoughtful mixtures framework and consistent histology-specific patterns, it makes the hypothesis substantially harder to dismiss.” He also noted that the cohort “is more highly educated and less racially diverse than the US female population, limiting direct extrapolation to the populations bearing the heaviest uterine cancer burden.”

The JAMA Network media release, issued at 11:00 a.m. Eastern time on July 22, 2026, restated the paper’s Key Points and did not go beyond them.

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What Remains Unknown

• Whether the link is causal. Two cohorts, Iowa and California, now point the same way for trihalomethanes and endometrial cancer, but neither measured exposure in the body.
• Which chemical matters, if any. The individual trihalomethanes were correlated with one another (Spearman coefficients 0.31 to 0.91), so the analysis cannot cleanly separate chloroform from its relatives. Only the regulated byproducts were studied.
• Which route matters. Drinking, breathing in shower steam and skin contact all contribute; the study could not tell them apart.
• Whether the haloacetic acid signal for nonendometrioid tumours holds up with longer records and more cases.
• Whether the findings apply to other groups, including Black women, who, the paper notes, have a higher uterine cancer mortality rate than White women. The commentary writes that “replication is needed in cohorts with greater racial, geographic, and socioeconomic diversity.”
• Whether biomarkers would confirm it. The commentary names urinary haloacetic acids and blood trihalomethanes after showering as measures that “would address the persistent ecological gap in this literature.”

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Sources and Primary Documents

Every figure attributed to the study above was taken from the paper’s open-access full text (text and Tables 1–4), not from the press release. The identifiers were checked against PubMed and Crossref.

1. Spaur M, Marcus Post L, Beane Freeman LE, Medgyesi DN, Fisher JA, Madrigal JM, et al. (2026). Drinking Water Contaminant Exposures and Risk of Uterine Cancer. JAMA Network Open 9(7):e2624391. — doi:10.1001/jamanetworkopen.2026.24391 · PubMed PMID: 42485040 · full text PMC13392805
2. Abohashem S (2026). Drinking Water Disinfection Byproducts and Uterine Cancer—A Modifiable Environmental Exposure Hiding in Plain Sight. JAMA Network Open 9(7):e2624398 (invited commentary). — doi:10.1001/jamanetworkopen.2026.24398 · PubMed PMID: 42485047
3. JAMA Network (July 22, 2026). Media release: Drinking Water Contaminant Exposures and Risk of Uterine Cancer. — media.jamanetwork.com
4. US Environmental Protection Agency. National Primary Drinking Water Regulations (table of maximum contaminant levels). — epa.gov
5. US Environmental Protection Agency. Stage 1 and Stage 2 Disinfectants and Disinfection Byproducts Rules (with the 1979, 1998 and 2006 Federal Register notices). — epa.gov

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Key Research Papers

Background papers, in the order this article uses them. Each entry was checked against PubMed and Crossref before it was written down.

1. Medgyesi DN, Trabert B, Sampson J, Weyer PJ, Prizment A, Fisher JA, et al. (2022). Drinking Water Disinfection Byproducts, Ingested Nitrate, and Risk of Endometrial Cancer in Postmenopausal Women. Environmental Health Perspectives 130(5):57012. — PubMed PMID: 35622390
2. Villanueva CM, Fernández F, Malats N, Grimalt JO, Kogevinas M (2003). Meta-analysis of studies on individual consumption of chlorinated drinking water and bladder cancer. Journal of Epidemiology and Community Health 57(3):166-173. — PubMed PMID: 12594192
3. Villanueva CM, Cantor KP, Cordier S, Jaakkola JJ, King WD, Lynch CF, et al. (2004). Disinfection byproducts and bladder cancer: a pooled analysis. Epidemiology 15(3):357-367. — PubMed PMID: 15097021
4. Costet N, Villanueva CM, Jaakkola JJ, Kogevinas M, Cantor KP, King WD, et al. (2011). Water disinfection by-products and bladder cancer: is there a European specificity? A pooled and meta-analysis of European case-control studies. Occupational and Environmental Medicine 68(5):379-385. — PubMed PMID: 21389011
5. Villanueva CM, Cantor KP, Grimalt JO, Malats N, Silverman D, Tardon A, et al. (2007). Bladder cancer and exposure to water disinfection by-products through ingestion, bathing, showering, and swimming in pools. American Journal of Epidemiology 165(2):148-156. — PubMed PMID: 17079692
6. Beane Freeman LE, Cantor KP, Baris D, Nuckols JR, Johnson A, Colt JS, et al. (2017). Bladder Cancer and Water Disinfection By-product Exposures through Multiple Routes: A Population-Based Case-Control Study (New England, USA). Environmental Health Perspectives 125(6):067010. — PubMed PMID: 28636529
7. Rahman MB, Driscoll T, Cowie C, Armstrong BK (2010). Disinfection by-products in drinking water and colorectal cancer: a meta-analysis. International Journal of Epidemiology 39(3):733-745. — PubMed PMID: 20139236
8. Evlampidou I, Font-Ribera L, Rojas-Rueda D, Gracia-Lavedan E, Costet N, Pearce N, et al. (2020). Trihalomethanes in Drinking Water and Bladder Cancer Burden in the European Union. Environmental Health Perspectives 128(1):17001. — PubMed PMID: 31939704
9. Spaur M, Medgyesi DN, Bangia K, Madrigal JM, Hurwitz LM, Beane Freeman LE, et al. (2025). Drinking water source and exposure to regulated water contaminants in the California Teachers Study cohort. Journal of Exposure Science & Environmental Epidemiology 35(3):454-465. — PubMed PMID: 39003368
10. Richardson SD, Plewa MJ, Wagner ED, Schoeny R, Demarini DM (2007). Occurrence, genotoxicity, and carcinogenicity of regulated and emerging disinfection by-products in drinking water: a review and roadmap for research. Mutation Research 636(1-3):178-242. — PubMed PMID: 17980649

PubMed Topic Searches

1. PubMed: Trihalomethanes and endometrial cancer
2. PubMed: Disinfection byproducts and bladder cancer
3. PubMed: Haloacetic acids, drinking water and cancer
4. PubMed: California Teachers Study and drinking water

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Connections

• News Archive
• Endometrial Cancer — the cancer of the uterine lining, its risk factors and research
• Bladder Cancer — the cancer most studied in relation to disinfection byproducts
• Colorectal Cancer — another cancer examined in byproduct research
• Arsenic — a drinking-water contaminant with no association in this study
• Uranium — a natural water contaminant, also null here
• Nitrates and Nitrites — the third contaminant the study found no link with
• PFAS — the “forever chemicals” also found in drinking water
• Household Chemicals — includes bleach, which releases chloroform in use
• Preventing Cryptosporidiosis — a waterborne parasite that resists chlorine disinfection
• Fluoride in Water — the other chemical added to many public water supplies
• Menopause and HRT — hormone therapy, a uterine cancer risk factor examined in the study
• Toxins — the site’s section on environmental and dietary toxins

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