Serum high-density lipoprotein cholesterol, metabolic profile, and breast cancer risk.
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 (P(trend) =.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 > or =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; P(trend)<.001; P(interaction) =.001).


CONCLUSIONS
Low HDL-C, as part of the metabolic syndrome, is associated with increased postmenopausal breast cancer risk.
Section of Epidemiology and Medical Statistics, Institute of Community Medicine, Faculty of Medicine, University of Tromsø, Tromsø, Norway. anne-sofie.furberg@ism.uit.no
Anne-Sofie
AS
Furberg
Marit Bragelien
MB
Veierød
Tom
T
Wilsgaard
Leslie
L
Bernstein
Inger
I
Thune
D000293:Adolescent; D000328:Adult; D000428:Alcohol Drinking / Q000009:adverse effects; D001794:Blood Pressure; D001827:Body Height; D001835:Body Weight; D001943:Breast Neoplasms / Q000097:blood / Q000453:epidemiology* / Q000209:etiology* / Q000503:physiopathology; D008076:Cholesterol, HDL / Q000097:blood*; D015986:Confounding Factors, Epidemiologic; D003276:Contraceptives, Oral / Q000008:administration & dosage; D004041:Dietary Fats / Q000008:administration & dosage; D002149:Energy Intake; D015340:Epidemiologic Research Design; D015914:Estrogen Replacement Therapy; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D006973:Hypertension / Q000150:complications; D008019:Life Style; D008055:Lipids / Q000097:blood; D024821:Metabolic Syndrome / Q000097:blood / Q000150:complications* / Q000453:epidemiology / Q000209:etiology / Q000503:physiopathology; D008875:Middle Aged; D009043:Motor Activity; D009664:Norway / Q000453:epidemiology; D009765:Obesity / Q000150:complications; D010298:Parity; D017698:Postmenopause; D017697:Premenopause; D015995:Prevalence; D012042:Registries; D018570:Risk Assessment; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects
D008076:Cholesterol, HDL; D003276:Contraceptives, Oral; D004041:Dietary Fats; D008055:Lipids