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JNCI Journal of the National Cancer Institute 2004 96(15):1152-1160; doi:10.1093/jnci/djh216
© 2004 by Oxford University Press
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© 2004 Oxford University Press

ARTICLE

Serum High-Density Lipoprotein Cholesterol, Metabolic Profile, and Breast Cancer Risk

Anne-Sofie Furberg, Marit Bragelien Veierød, Tom Wilsgaard, Leslie Bernstein, Inger Thune

Affiliations of authors: Section of Epidemiology and Medical Statistics, Institute of Community Medicine, Faculty of Medicine, University of Tromsø, Tromsø, Norway (ASF, TW, IT); Section of Medical Statistics, University of Oslo, Oslo, Norway (BV); Keck School of Medicine, University of Southern California, Los Angeles (LB); Ullevål University Hospital, Oslo (IT)

Correspondence to: Anne-Sofie Furberg, MD, PhD, Institute of Community Medicine, Faculty of Medicine, University of Tromsø, N-9037 Tromsø, Norway (e-mail: anne-sofie.furberg{at}ism.uit.no)

Background: The prevalence of metabolic syndrome (obesity, glucose intolerance, low serum high-density lipoprotein cholesterol [HDL-C], high serum triglycerides, hypertension) is high and increasing in parallel with an increasing breast cancer incidence worldwide. HDL-C represents an important aspect of the syndrome, yet its role in breast cancer is still undefined. Methods: In two population-based screening surveys during 1977–1983 and 1985–1987, serum HDL-C was assayed enzymatically among 38 823 Norwegian women aged 17–54 years at entry. Height, weight, blood pressure, serum lipids, fat and energy intake, physical activity, parity, oral contraceptive use, hormone therapy use, alcohol intake, and tobacco use were also assessed. We used Cox proportional hazards modeling to estimate the relative risk (RR) of breast cancer associated with serum HDL-C levels and to adjust for potential confounding variables. We performed stratified analyses to evaluate effect modification by body mass index (BMI) and menopausal status. All statistical tests were two-sided. Results: During a median follow-up of 17.2 years, we identified 708 cases of invasive breast cancer. In multivariable analysis, the risk of postmenopausal breast cancer was inversely related to quartile of HDL-C (Ptrend = .02). Among women with HDL-C above 1.64 mmol/L (highest quartile) versus below 1.20 mmol/L (lowest quartile), the relative risk was 0.75 (95% confidence interval [CI] = 0.58 to 0.97). The HDL-C association was confined to women in the heavier subgroup (BMI ≥25 kg/m2), for whom the relative risk of postmenopausal breast cancer in those with HDL-C above 1.64 mmol/L versus below 1.20 mmol/L was 0.43 (95% CI = 0.28 to 0.67; Ptrend<.001; Pinteraction = .001). Conclusion: Low HDL-C, as part of the metabolic syndrome, is associated with increased postmenopausal breast cancer risk.



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