Height, sitting height, and leg length in relation with breast cancer risk in the E3N cohort

Background: If height is a well-established risk factor for breast cancer, leg length and sitting height are usually considered as better candidate biomarkers of growth hormone exposure than height, respectively, in pre- and postpuberty. Methods: Risk of breast cancer associated with quartiles of height, sitting height, and leg length were estimated in the French E3N cohort (N = 50,704, including 2,065 breast cancer cases), stratified on both menopausal and hormone receptor statuses. Results: Height was associated with an increased postmenopausal breast cancer risk [HR = 1.22 (1.06-1.41) when comparing extreme categories, P_trend = 0.002], which was exclusively driven by the association with leg length [HR = 1.21 (1.05-1.39), P_trend = 0.013] and not sitting height [HR = 1.03 (0.89-1.18), P_trend = 0.379]. Leg length was associated with an increased ER⁺ breast cancer risk in postmenopausal [HR = 1.24 (1.06-1.46), P_trend = 0.004], whereas sitting height was associated with a borderline decreased ER^- premenopausal breast cancer risk [HR = 0.45 (0.20-1.01), P_trend = 0.011]. The positive associations observed in the overall population between leg length and breast cancer risk were actually restricted to women who had a short birth length [HR = 1.82 (1.22-2.72), P_trend = 0.022] and those with a low birth weight [HR = 1.43 (1.00-2.04), P_trend = 0.054]. Conclusion: The two components of height risk are differentially associated with breast cancer risk: leg length with an increased risk of postmenopausal ER ⁺ tumors and sitting height with a decreased risk of premenopausal ER^- tumors. Impact: Future prospective studies should no longer consider height a single risk factor for breast cancer risk.