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. 2017 Jun 28;106(2):637–649. doi: 10.3945/ajcn.116.150912

TABLE 3.

Top 20 diet-related serum metabolites associated with ER+ breast cancer in a nested case-control study within the PLCO cancer screening trial1

90th vs. 10th percentile3
 90th vs. 10th percentile4
Metabolite Food Correlation coefficient2 Multivariate-adjusted OR (95% CI) P BMI and multivariate-adjusted OR (95% CI) P
α-Hydroxyisovalerate Alcohol (liquor) +0.23 2.22 (1.51, 3.29) 6.0 × 10−5* 2.23 (1.50, 3.32) 7.4 × 10−5*
4-Androsten-3β,17β-diol disulfate-(2) Alcohol +0.16 2.13 (1.45, 3.13) 1.2 × 10−4* 2.08 (1.41, 3.07) 2.4 × 10−4*
4-Androsten-3β,17β-diol monosulfate-(1) Alcohol (beer) +0.16 2.11 (1.43, 3.11) 1.7 × 10−4* 2.06 (1.39, 3.05) 3.0 × 10−4*
DHEAS Alcohol +0.16 1.96 (1.32, 2.91) 9.0 × 10−4* 1.93 (1.30, 2.88) 1.2 × 10−3*
5α-Androstan-3α,17β-diol disulfate Alcohol (beer, liquor) +0.15 1.92 (1.31, 2.80) 8.1 × 10−4* 1.89 (1.29, 2.80) 1.1 × 10−3*
Pregnen-diol disulfate Alcohol (beer) +0.16 1.92 (1.29, 2.84) 1.2 × 10−3* 1.88 (1.27, 2.79) 1.8 × 10−3*
4-Androsten-3β,17β-diol monosulfate-(2) Alcohol (beer, liquor, wine) +0.24 1.92 (1.34, 2.76) 4.2 × 10−4* 1.87 (1.30, 2.70) 7.6 × 10−4*
4-Androsten-3β,17β-diol disulfate-(1) Alcohol (beer, liquor) +0.26 1.92 (1.30, 2.84) 1.1 × 10−3* 1.87 (1.25, 2.77) 2.1 × 10−3*
Caprate-(10:0) Butter +0.15 1.82 (1.24, 2.67) 2.3 × 10−3* 1.81 (1.23, 2.67) 2.7 × 10−3*
γ-CEHC Desserts +0.16 1.85 (1.24, 2.77) 2.7 × 10−3* 1.80 (1.20, 2.70) 4.7 × 10−3*
Ethyl glucuronide Alcohol (beer, liquor, wine) +0.36 1.73 (1.23, 2.41) 1.5 × 10−3* 1.76 (1.26, 2.47) 1.1 × 10−3*
α-Tocopherol Multivitamin, vitamin E supplements +0.41 0.56 (0.37, 0.84) 5.3 × 10−3* 0.56 (0.37, 0.85) 6.8 × 10−3*
Etiocholanolone glucuronide Alcohol (beer) +0.18 1.76 (1.16, 2.67) 7.7 × 10−3* 1.74 (1.15, 2.65) 9.2 × 10−3*
δ-Tocopherol Margarine +0.15 1.80 (1.17, 2.79) 8.0 × 10−3* 1.74 (1.12, 2.71) 1.5 × 10−2*
2-Hydroxy-3-methylvalerate Liquor +0.15 1.74 (1.15, 2.65) 9.0 × 10−3* 1.72 (1.12, 2.62) 1.2 × 10−2*
Pyroglutamine Red meat −0.16 1.60 (1.08, 2.38) 2.1 × 10−2* 1.59 (1.07, 2.37) 2.3 × 10−2*
10-Undecenoate-(11:1n–1) Butter, cheese, ice cream +0.18 1.59 (1.07, 2.36) 2.2 × 10−2* 1.59 (1.07, 2.36) 2.3 × 10−2*
5α-Androstan-3β,17β-diol disulfate Alcohol (beer, liquor) +0.15 1.53 (1.08, 2.17) 1.6 × 10−2* 1.50 (1.06, 2.13) 2.3 × 10−2*
2-Hydroxyoctanoate Fried potatoes +0.15 1.47 (1.04, 2.08) 3.1 × 10−2* 1.46 (1.03, 2.07) 3.2 × 10−2*
Ergothioneine Alcohol (beer, liquor), shellfish +0.21 1.41 (1.01, 1.95) 4.3 × 10−2 1.42 (1.02, 1.97) 3.8 × 10−2
1

n = 418 incident cases and 437 matched controls. The top 20 metabolites are presented to highlight all significant associations with a consistent number of results for the overall breast cancer and breast cancer subtype analyses. For dietary exposure, “Alcohol” refers to all alcohol types combined. Specific alcohol type associations are shown in parentheses. *Significant after controlling for multiple comparisons by using a false discovery rate <0.2. DHEAS, dehydroisoandrosterone sulfate; ER+, estrogen receptor–positive; PLCO, Prostate, Lung, Colorectal, and Ovarian; γ-CEHC, γ-carboxyethyl hydrochroman.

2

Direction and magnitude of correlation between dietary exposure and metabolite; the highest correlation is presented for metabolites correlated with multiple foods.

3

Risks at the 90th compared with the 10th percentile of the distribution of log-relative metabolite intensity. Conditional logistic regression, controlling for age at blood draw (years), race/ethnicity (non-Hispanic white or other), age at menarche (<12 y, 12–13 y or missing, or ≥14 y), age at first child and number of live births (nulliparous, <20 y and ≥1 live birth, 20–29 y and 1–2 live births, 20–29 y and ≥3 live births or missing, or ≥30 y and ≥1 live birth), type of menopause and age at menopause (natural and <45 y, natural and 45–49 y, natural and 50–54 y, natural and ≥55 y, bilateral oophorectomy or drug therapy or radiation, or hysterectomy or missing), menopausal hormone therapy use (never, former or current), history of benign breast disease (no or missing or yes), first-degree female family history of breast cancer (no or missing, or yes), education (≤12 y, post–high school training besides college, some college or missing, college, or postgraduate), smoking history (never or missing, former, or current), drinking history (never or missing, former, or current), diabetes history (no or yes), vigorous physical activity (in hours per week; none, <1, 1, 2, 3, ≥4, or missing), and daily caloric intake (quintiles). Alcohol-related metabolites were not adjusted for self-reported alcohol use.

4

Risks at the 90th compared with the 10th percentile of the distribution of log-relative metabolite intensity. Conditional logistic regression with control for the same covariates as in footnote 3, with additional control for BMI (in kg/m2; <25, 25 to <30, ≥30, or missing).