Table 4.
BMI-associated metabolites associated with postmenopausal breast cancer and estrogen receptor–positive breast cancer in forward selection models*
| Breast cancer |
ER+ breast cancer |
||||||
|---|---|---|---|---|---|---|---|
| Metabolite† | Chemical class | OR (95% CI)‡ | P | Q§ | OR | P | Q |
| 16a-hydroxy DHEA 3-sulfate | Lipid | 1.65 (1.22 to 2.22) | .001 | 0.07 | 1.84 (1.27 to 2.67) | .001 | 0.09 |
| Allo-isoleucine | Amino acid | – | – | – | 1.76 (1.23 to 2.51) | .002 | 0.09 |
| 2-methylbutyrylcarnitine | Amino acid | – | – | – | 1.89 (1.22 to 2.91) | .004 | 0.09 |
| 3-methylglutarylcarnitine | Amino acid | 1.67 (1.21 to 2.30) | .002 | 0.07 | 1.91 (1.23 to 2.96) | .004 | 0.09 |
Multivariable odds ratios and 95% confidence intervals are provided for a comparison of 90th and 10th percentile levels of BMI-associated metabolites. BMI = body mass index; CI = confidence interval; OR = odds ratio.
Odds ratios were estimated with conditional logistic regression and adjusted for age at blood draw (years), age at menarche (≤12 years, 12–13 years or missing, ≥14 years), age at first live birth and number of live births (nulliparous, age ≤19 years and one or more live births, age 20–29 years with one or two live births, age 20–29 with three or more live births or missing, age 30+ with one or more live births), type of menopause and age at menopause (natural and <45 years, natural and 45–49 years, natural and 50–54 years, natural and ≥55 years, bilateral oophorectomy/surgery, drugs/radiation, hysterectomy or missing), menopausal hormone therapy use at blood draw (never, former, current), history of benign breast disease (no or missing, yes), first-degree family history of breast cancer (no or missing, yes), race/ethnicity (non-Hispanic white or missing, other), education (high school or less, post–high school training besides college, some college or missing, completed college, postgraduate), smoking history (never, former, current), diabetes history (no or missing, yes), leisure time physical activity (none, less than one hour/week, one hour/week, two hours/week, three hours/week, four or more hours/week, missing), and body mass index (<25 kg/m2, 25.0–<30 kg/m2 or missing, >30 kg/m2).
The models include all metabolites statistically significantly associated with breast cancer or ER+ breast cancer (false discovery rate <0.2). Odds ratios and P values are based on mutually adjusted models. For breast cancer, 16a-hydroxy DHEA 3-sulfate and 3-methylglutarylcarnitine were included in the model. For ER+ breast cancer, 16a-Hydroxy DHEA 3-sulfate, Allo-isoleucine, 2-methylbutyrylcarnitine, and 3-methylglutarylcarnitine were included in the model. Forward selection models were used to identify a parsimonious set of metabolites statistically significantly and independently associated with risk. Specifically, models were constructed by adding the metabolite with the lowest P value to the model, retesting all remaining metabolites for statistical significance, and then adding the metabolite with the lowest P value from this new set. We did this until the false discovery rate threshold of 0.20 was reached.
The Q value is the estimated probability of a false discovery.