Lipid biomarkers and long-term risk of cancer in the Women's Health Study

Abstract

Background: Lipid biomarkers, such as HDL-cholesterol concentrations, have been shown to have positive, inverse, and null associations with total, breast, and colorectal cancer risks. Studies of novel lipid biomarkers, such as apolipoprotein A-I (apo A-I) and apolipoprotein B-100 (apo B-100), and cancer risk have been sparse, to our knowledge.

Objectives: We evaluated the prospective association of total, breast, colorectal, and lung cancers and cancer mortality with circulating lipid biomarkers in 15,602 female health professionals in the Women's Health Study (aged ≥45 y, free of cardiovascular disease and cancer, and without hormone replacement therapy or lipid-lowering medications at baseline).

Design: Cox regression models estimated HRs of cancer endpoints (19 y median follow-up) across quartiles 1 (reference) to 4 of each lipid biomarker after adjustment for cancer risk factors.

Results: Confirmed cases included 2163 incident cancer cases (864 breast, 198 colorectal, and 190 lung cancers) and 647 cancer deaths. Total cancer risk was significantly lower in the highest quartile of apo A-I (adjusted HR: 0.79; 95% CI: 0.70, 0.90; P-trend = 0.0008) and HDL cholesterol (HR: 0.85; 95% CI: 0.75, 0.97; P-trend = 0.01). For site-specific cancers, significant associations included colorectal cancer risk with HDL cholesterol (HR: 0.63; 95% CI; 0.41, 0.98; P-trend = 0.03), triglycerides (HR: 1.86; 95% CI: 1.17, 2.97; P-trend = 0.02), and apo B-100 (HR: 1.60; 95% CI: 1.03, 2.49; P-trend = 0.006) and lung cancer risk with HDL cholesterol (HR: 0.59; 95% CI: 0.38, 0.93; P-trend = 0.01). LDL cholesterol was not significantly associated with risk of total cancer or any site-specific cancers. In time-dependent models that were adjusted for the use of a lipid-lowering medication after baseline, these associations remained.

Conclusions: Lipids were associated with total, lung, and colorectal cancer risks in women. Lifestyle interventions for heart-disease prevention, which reduce apo B-100 or raise HDL cholesterol, may be associated with reduced cancer risk. The Women's Health Study was registered at clinicaltrials.gov as NCT00000479.

Keywords: cancer; lipids; metabolomics; triglycerides; women.

© 2016 American Society for Nutrition.

Figures

FIGURE 1

HRs per 1 SD for incident cancer events are shown on the y axis (log scale) for CHOL, HDL, TGGB, LDL, ApoA1, and ApoB. Incident cancer cases were as follows: total, n = 2163; lung, n = 190; colorectal, n = 198; and breast, n = 864. Values were evaluated with the use of Cox proportional hazard models. SD concentrations were as follows: CHOL, 209.2 mg/dL; HDL, 51.1 mg/dL; TGGBs, 133.8 mg/dL; LDL, 126.1 mg/dL; ApoA1, 142.3 mg/dL; and ApoB, 102.7 mg/dL. ApoA1, apolipoprotein A-I; ApoB, apolipoprotein B-100; CHOL, total cholesterol; HDL, HDL cholesterol; LDL, LDL cholesterol; TGGB, triglyceride.

FIGURE 2

HRs per 1 SD for cancer mortality events are shown on the y axis (log scale) for CHOL, HDL, TGGBs, LDL, ApoA1, and ApoB. Cancer death cases were as follows: total, n = 647; lung, n = 156; colorectal, n = 62; and breast. n = 80. Values were evaluated with the use of Cox proportional hazard models. SD concentrations were as follows: CHOL, 209.2 mg/dL; HDL, 51.1 mg/dL; TGGB, 133.8 mg/dL; LDL, 126.1 mg/dL; ApoA1, 142.3 mg/dL; and ApoB, 102.7 mg/dL. Categories for variables were as follows: treatment random assignment (aspirin, vitamin E, beta-carotene), hormone replacement therapy (past or none), cigarette smoking (never, past, or current), exercise [total kilocalories from exercise and the number of stairs taken per week (4 categories as follows: <200, 200 to <600, 600 to <1500, ≥ 1500)], alcohol consumption (continuous; grams per day), postmenopausal status (yes or no), family history of cancer (yes or no), aspirin use (current use >1 time/wk or no use), history of colon polyps (yes or no), history of fibrocystic or benign breast disease (yes or no), total vegetables and fruit intake (servings/d), history of mammogram (yes or no), age of menarche (≤11, 12, 13, or ≥14 y), gestational age in weeks at completion of first pregnancy lasting >6 mo (nulliparous, ≤29, or ≥30), and BMI (in kg/m2) in 5 categories (<18.5, 18.5 to <25, 25 to <30, 30 to <35, or ≥35; the reference group was 18.5 to <25). HRs were adjusted for the following variables—for total cancer: age, race, treatment random assignment, hormone replacement therapy, cigarette smoking, exercise, alcohol consumption, postmenopausal status, family history of cancer, aspirin use, history of colon polyps, history of fibrocystic or benign breast disease, total vegetable and fruit intake, history of mammogram, and BMI; for colorectal cancer: age, race, treatment random assignment, hormone replacement therapy, cigarette smoking, exercise, alcohol consumption, postmenopausal status, family history of cancer, aspirin use, history of colon polyps, total vegetable and fruit intake, history of mammogram, red meat intake, and BMI; for breast cancer: age, race, treatment random assignment, hormone replacement therapy, cigarette smoking, exercise, alcohol consumption, postmenopausal status, family history of cancer, aspirin use, history of colon polyps, history of fibrocystic or benign breast disease, total vegetable and fruit intake, history of mammogram, family history of breast cancer in mother or sister at <60 y of age, reproductive history, and BMI; and for lung cancer: age, race, treatment random assignment, hormone replacement therapy, cigarette smoking, exercise, alcohol consumption, postmenopausal status, family history of cancer, aspirin use, history of mammogram, and BMI. ApoA1, apolipoprotein A-I; ApoB, apolipoprotein B-100; CHOL, total cholesterol; HDL, HDL cholesterol; LDL, LDL cholesterol; TGGB, triglyceride.