Estrogen metabolism-related lifestyle score and risk of postmenopausal breast, endometrial, and ovarian cancers: findings from two large prospective cohort studies
Menée à l'aide de données de l'étude "Shanghai Women’s Health Study" et de l'essai "Prostate, Lung, Colorectal and Ovarian Screening Trial" portant au total sur 1 358 femmes ménopausées, cette étude analyse l'association entre des modes de vie favorisant le métabolisme des oestrogènes et le risque de cancer du sein, de l'endomètre ou de l'ovaire
High endogenous estrogen levels contribute to the etiology of hormone-related cancers. 2-hydroxylation (2-OH) of estrogen exhibits potential anti-tumorigenic properties. We hypothesized that lifestyle patterns related to the ratio of 2-OH pathway estrogen metabolites (EMs) 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 Shanghai Women’s Health Study (SWHS, n=723) and Prostate, Lung, Colorectal and Ovarian Screening Trial (PLCO, n=635), where blood (PLCO) or urine (SWHS) samples collected at baseline were profiled for parent estrogens and EMs. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of lifestyle scores with risk of breast, endometrial, and ovarian cancers in SWHS (N=35,453) and PLCO (N=26,565). The lifestyle scores explained 10-11% of total variance in the 2-OH EM/parent E ratio. In the SWHS, a higher score was associated with 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 comparing the highest to lowest quartile, respectively. The association was more apparent with estrogen receptor (ER)-positive than ER-negative breast cancer. Similar inverse associations were observed in the PLCO. Lifestyle patterns linked to elevated 2-OH of estrogen were associated with lower risk of postmenopausal breast and endometrial cancers. Our study provides evidence for lifestyle modifications for cancer prevention.
Cancer Prevention Research , résumé, 2026