Ran Tao

Supplementary Figure S2 shows prediction performance of the lifestyle score.

Supplementary Figure S4 shows foods and lifestyles selected to derive the lifestyle score in the PLCO.

Supplementary Table S6 shows results for stratified analyses of endometrial cancer risk.

High endogenous estrogen levels contribute to the etiology of hormone-related cancers. 2-hydroxylation (2-OH) of estrogen exhibits potential antitumorigenic properties. We hypothesized that lifestyle patterns related to the ratio of 2-OH pathway estrogen metabolites (EM) to parent estrogens (2-OH EM/parent E ratio) might lower estrogen-related cancer risk. We applied elastic net regularized regression to derive lifestyle scores correlated with the 2-OH EM/parent E ratio separately using data from subsets of cancer-free, postmenopausal women in the Shanghai Women’s Health Study (SWHS, n = 723) and the Prostate, Lung, Colorectal and Ovarian Screening Trial (PLCO, n = 635), in which blood (PLCO) or urine (SWHS) samples collected at baseline were profiled for parent Es and EMs. Cox proportional hazards models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for associations of lifestyle scores with the risk of breast, endometrial, and ovarian cancers in SWHS (N = 35,453) and PLCO (N = 26,565). The lifestyle scores explained 10% to 11% of the total variance in the 2-OH EM/parent E ratio. In the SWHS, a higher score was associated with a 29% (HR = 0.71; 95% CI, 0.57–0.88; Ptrend < 0.001) and 61% (HR = 0.39; 95% CI, 0.21–0.71; Ptrend < 0.001) lower risk of breast and endometrial cancers when comparing the highest with the lowest quartile, respectively. The association was more apparent with estrogen receptor (ER)-positive than with ER-negative breast cancer. Similar inverse associations were observed in the PLCO. Lifestyle patterns linked to elevated 2-OH of estrogen were associated with a lower risk of postmenopausal breast and endometrial cancers. Our study provides evidence for lifestyle modifications for cancer prevention.Prevention Relevance:Elevated estrogen 2-OH has been linked to reduced breast cancer risk. We showed that lifestyle patterns increasing the 2-OH EM/parent E ratio were associated with lower postmenopausal breast and endometrial cancer risk. Our findings suggest that targeted lifestyle modifications may benefit postmenopausal women with a low 2-OH EM/parent E ratio.

Supplementary Table S1 shows selected baseline characteristics of study participants eligible for endometrial cancer analyses.

Supplementary Figure S3 shows foods and lifestyles selected to derive the lifestyle score in the SWHS.

Supplementary Table S4 shows foods and lifestyles selected to derive the lifestyle score in the PLCO.

Supplementary Table S5 shows results for stratified analyses of breast cancer risk.