摘要：Background:
Disinfection byproducts (DBPs) and
N-nitroso compounds (NOC), formed endogenously after nitrate ingestion, are suspected endometrial carcinogens, but epidemiological studies are limited.
Objectives:
We investigated the relationship of these exposures with endometrial cancer risk in a large prospective cohort.
Methods:
Among postmenopausal women in the Iowa Women’s Health Study cohort, we evaluated two major classes of DBPs, total trihalomethanes (TTHM) and five haloacetic acids (HAA5), and nitrate-nitrogen (
NO
3
-N
) in public water supplies (PWS) in relation to incident primary endometrial cancer (1986–2014). For women using their PWS
>
10
y
at enrollment (
n
=
10
,
501
;
cases
=
261
), we computed historical averages of annual concentrations; exposures were categorized into quantiles and when possible
≥
95
th
percentile. We also computed years of PWS use above one-half the U.S. maximum contaminant level (
>½
MCL
;
40
μ
g
/
L
TTHM;
30
μ
g
/
L
HAA5;
5
mg
/
L
NO
3
-N
). Dietary nitrate/nitrite intakes were estimated from a food frequency questionnaire. We estimated hazard ratios (HR) and 95% confidence intervals (CI) via Cox models adjusted for age, endometrial cancer risk factors [e.g., body mass index, hormone replacement therapy (HRT)], and mutually adjusted for
DBPs
or
NO
3
-N
. We evaluated associations for low-grade (
cases
=
99
) vs. high-grade (
cases
=
114
) type I tumors. We assessed interactions between exposures and endometrial cancer risk factors and dietary factors influencing NOC formation.
Results:
Higher average concentrations of DBPs (95th percentile: TTHM
≥
93
μ
g
/
L
, HAA5
≥
49
μ
g
/
L
) were associated with endometrial cancer risk (TTHM:
HR
95
vsQ
1
=
2.19
, 95% CI: 1.41, 3.40; HAA5:
HR
95
vsQ
1
=
1.84
, 95% CI: 1.19, 2.83;
p
trend
<
0.01
). Associations were similarly observed for women greater than median years of PWS use with levels
>½
MCL
, in comparison with zero years (TTHM:
HR
36
+
vs
0
y
=
1.61
, 95% CI: 1.18, 2.21; HAA5:
HR
38
+
vs
0
y
=
1.85
, 95% CI: 1.31, 2.62). Associations with DBPs appeared stronger for low-grade tumors (TTHM:
HR
Q
4
vsQ
1
=
2.12
, 95% CI: 1.17, 3.83;
p
-trend
=
0.008
) than for high-grade tumors (TTHM:
HR
Q
4
vsQ
1
=
1.40
, 95% CI: 0.80, 2.44;
p
-trend
=
0.339
), but differences were not statistically significant (
p
-heterogeneity
=
0.43
). Associations with TTHM were stronger among ever HRT users than non-HRT users (
p
-interaction
<
0.01
). We observed no associations with
NO
3
-N
in drinking water or diet.
Discussion:
We report novel associations between the highest DBP levels and endometrial cancer for our Iowa cohort that warrant future evaluation.
https://doi.org/10.1289/EHP10207
