Abstract A08: Lipid biomarkers and cancer risk: Long-term observational follow-up of cancer in the Women's Health Study
Authors: Chandler Paulette D. , Zhang Shumin , Lin Jennifer H. , Manson JoAnn E. , Buring Julie E. , Moorthy M V. , Ridker Paul , McMahon Kevin P. , Lee I-Min , Song Yiqing , Wang Lu 
Published: October 2015

Background: Lipids are involved in the inflammatory response and are the major cell membrane components essential for various biological functions including cell growth and division of normal and malignant tissues. Circulating lipoproteins and lipids have different associations with cancer risk.

Objective: To determine whether baseline levels of blood lipid markers were associated with subsequent cancer risk in initially healthy women free of cancer and cardiovascular disease.

Design: Observational follow-up of a randomized trial. The primary cancer end points included total (excluding nonmelanoma skin), breast, colorectal, ovarian, and endometrial cancers, and cancer mortality.

Setting: A total of 39,876 healthy female health professionals aged 45 years or older in the Women's Health Study (WHS, ClinicalTrials.gov: NCT00000479. Baseline blood was collected from 27,495 women with median follow-up of 19 years.

Methods: We examined the prospective association between baseline total cholesterol [TC], low-density lipoprotein cholesterol [LDL-C], high-density lipoprotein cholesterol [HDL-C], triglycerides [TG]), apolipoprotein A-I [Apo A-I] and B100 [Apo B100] and risk of total cancer, breast, ovarian, endometrial, and colorectal cancer among all women with no prior diagnosis of cancer in the WHS. Plasma lipid biomarkers were categorized into quartiles. All cancer endpoints were confirmed from medical records. We used Cox proportional Hazard Regression to estimate hazard ratios (HRs) representing comparison of quartile 4 (highest) to quartile 1 (lowest) adjusted for cancer risk factors.

Results: A total of 4,001 incident cancer cases (1657 breast, 345 colorectal, 315 endometrial, and 165 ovarian) and 1175 cancer deaths were confirmed. Most of the lipid biomarkers were not significantly associated with total cancer risk, except a significant inverse association was observed between ApoA-I and total cancer incidence (adjusted HR: 0.83 [95% CI, 0.75 to 0.92]; ptrend&lt;0.0001). For individual cancer site, we observed significant associations for several lipids with colorectal cancer for TG (HR: 1.61 [1.15 to 2.24]; ptrend&lt;0.001), Apo B100 (HR: 1.41 [1.02 to1.94]; ptrend=0.01), TG/HDL-C (HR, 1.76 [1.25 to 2.48]; ptrend=0.003) , and HDL-C (HR: 0.68 [0.49 to 0.95]; ptrend=0.01). Similarly, an increased ovarian cancer risk was seen with higher TC (HR, 1.52 [CI, 0.98 to 2.35]; ptrend = 0.02). However, both TG and TG/HDL were found significantly inversely associated with breast cancer risk (TG:HR, 0.78 [CI, 0.67 to 0.91]; ptrend = 0.002; TG/HDL: HR, 0.77 [CI, 0.67 to 0.90]; ptrend = 0.001). LDL-C was not significantly associated with risk of total cancer or any site-specific cancers.

Conclusions: In this prospective cohort of middle-aged and older US women, we found significant associations between plasma lipid markers including TC, HDL-C, TG, Apo A1, and Apo B100 and total cancer and some site-specific cancers. Specifically, colorectal cancer is associated with various lipids. Future studies are needed to confirm or refute these findings and explore the mechanisms underlying these associations.

Citation Format: Paulette D. Chandler, Shumin Zhang, Jennifer H. Lin, JoAnn E. Manson, Julie E. Buring, M V. Moorthy, Paul Ridker, Kevin P. McMahon, I-Min Lee, Yiqing Song, Lu Wang. Lipid biomarkers and cancer risk: Long-term observational follow-up of cancer in the Women's Health Study. [abstract]. In: Proceedings of the Thirteenth Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2014 Sep 27-Oct 1; New Orleans, LA. Philadelphia (PA): AACR; Can Prev Res 2015;8(10 Suppl): Abstract nr A08.