Plasma Lipid Markers and Cancer Risk

Summary

Principal Investigator: Lu Wang
Abstract: DESCRIPTION (provided by applicant): In this application, we will take advantage of the existing data of plasma lipid markers in 28,345 Women's Health Study (WHS) participants and conduct a detailed, prospective cohort evaluation of standard lipid markers (total cholesterol, low-density lipoprotein cholesterol (LDL-C), HDL-C, triglycerides), and novel lipid markers (apolipoprotein A-1 (Apo A-1) and Apo B100), as well as long-term use of statins in relation to risk of total invasive cancer and breast, colorectal and endometrial cancer. Blood lipids may affect cancer risk through their association with insulin resistance, inflammation and oxidative stress. Statins have anti- inflammatory, proapoptotic, and antiproliferative effects, which may make them relevant to cancer prevention. Also, we will evaluate these associations by factors that affect plasma lipid levels (e.g., menopausal status, body mass index, physical activity, postmenopausal hormone use, alcohol intake, and other plasma obesity- related markers), as well as by tumor characteristics (e.g., estrogen receptor status). We will also address the issue that the preclinical disease may alter blood lipid levels by conducting an analysis of excluding the first 2 years of follow-up. By June 2011, with a mean follow-up duration of 17 years, we expect 3,506 confirmed incident invasive cancers, including 1,473 breast cancers, 338 colorectal cancers, and 304 endometrial cancers in 28,345 women who provided a baseline blood sample and were free of cancer and cardiovascular disease at baseline. Standard and novel lipid markers were already measured in these 28,345 blood samples. Thus, this proposed study affords a unique and extraordinary opportunity to conduct a prospective cohort analysis of plasma lipid markers and cancer risk. This proposed study is innovative as the associations between plasma Apo A-1 and Apo B100 and cancer risk are largely unexplored in prospective studies. Few studies have examined blood lipid markers and long-term statin use in relation to endometrial cancer risk. This proposed study will be the first evaluation of the relations between plasma Apo A-1 and Apo B100 and overall cancer risk and between Apo B100 and endometrial cancer risk, as well as the first prospective evaluation of Apo A-I and risk of breast and endometrial cancer. This study also has numerous other strengths, including the prospective cohort study design, large sample size (n = 28,345), large numbers of cases (n = 3,506), long duration of follow-up (17 years), excellent environment, availability of other plasma obesity-related markers, detailed information on covariates and tumor characteristics. The ongoing WHS provides follow-up, ascertainment and documentation of cancer cases, and data on biomarkers, statin use, and covariates. Thus, this proposed study affords a unique opportunity to test promising hypotheses about cancer risk in an exceptionally cost-efficient manner. Findings from this study will help clarify the role of plasma lipid markers in identifying women at high risk of cancer who would most benefit from chemoprevention or increased screening and the role of long-term use of statins in cancer chemoprevention. PUBLIC HEALTH RELEVANCE: The proposed study will conduct a comprehensive, prospective cohort evaluation of standard lipid markers of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, and triglycerides, and novel lipid markers of apolipoproteins A-1 and B100 , as well as long-term use of statins in relation to risk of total invasive cancer and breast, colorectal and endometrial cancer in the Women's Health Study. Findings from this study will help clarify the role of plasma lipid markers in identifying women at high risk of cancer who would most benefit from chemoprevention or increased screening and the role of long-term use of statins in cancer chemoprevention.
Funding Period: 2012-09-20 - 2014-08-31
more information: NIH RePORT

Detail Information

Research Grants30

  1. Women's Health Study: Continued Follow-up
    I Min Lee; Fiscal Year: 2013
    ..1 ..
  2. Assessing the role of androgens in breast cancer risk
    Susan E Hankinson; Fiscal Year: 2013
    ....
  3. Breast and Other Cancers in the California Teachers Cohort
    Leslie Bernstein; Fiscal Year: 2013
    ....
  4. Research and Mentoring on Energetic Factors and Cancer: Established Investigator
    Leslie Bernstein; Fiscal Year: 2013
    ....
  5. Susceptibility Markers for a Breast-Colon Cancer Phenotype
    Mala Pande; Fiscal Year: 2013
    ..The cancer prevention goal of this research is the identification of individuals at high risk for cancer development for whom screening and early detection would be most beneficial in reducing the burden of cancer. ..
  6. Metabolic Syndrome and Breast Cancer: Effects of a Combined Exercise Intervention
    Christina Dieli-Conwright; Fiscal Year: 2013
    ..Survival rates for breast cancer are relatively high translating to a need for healthy living to diminish risk of other diseases such as diabetes and cardiovascular disease. ..
  7. Transdisciplinary Studies of Genetic Variation in Colorectal Cancer
    Stephen B Gruber; Fiscal Year: 2013
    ..abstract_text> ..
  8. Bridging Research, Innovation, Training &Education Solutions for Minority Health
    Vickie M Mays; Fiscal Year: 2013
    ..abstract_text> ..
  9. DIETARY AND HORMONAL DETERMINANTS OF CANCER IN WOMEN
    Meir Stampfer; Fiscal Year: 2013
    ..abstract_text> ..
  10. Depression, Estrogen Replacement, and Cardiovascular Health in the Perimenopause
    David R Rubinow; Fiscal Year: 2013
    ..abstract_text> ..
  11. Early Life Determinants of Accelerated Pubertal Development in Adolescent Girls
    Ai Kubo; Fiscal Year: 2013
    ..Kubo to develop successful R01 research to further elucidate early life determinants of pubertal onset and other cancer risk factors. ..
  12. EARLY EVENTS IN ALZHEIMER PATHOGENESIS
    SUE TILTON GRIFFIN; Fiscal Year: 2013
    ..The synergy between our aims, approaches, and measures will enable us to meet our goal of defining early cellular interactions toward development of rational interventions in AD. ..
  13. NEW MODALITIES FOR TREATMENT OF PAIN AND DRUG ABUSE
    Victor J Hruby; Fiscal Year: 2013
    ....
  14. Inflammatory responses of vascular cells
    Paul L Fox; Fiscal Year: 2013
    ..abstract_text> ..
  15. Urate as a Predictor of Parkinson's Disease Risk and Progression
    Alberto Ascherio; Fiscal Year: 2013
    ..Because blood levels of urate can be modified with existing drugs, the proposed project could lead to novel approaches to the prevention and treatment of Parkinson's disease. ..
  16. Weight Loss &Cancer Biomarkers in Women: 0xidative Stress &Inflammation
    ANNE M MCTIERNAN; Fiscal Year: 2013
    ..The results of this novel study will elucidate potential mechanisms linking energy balance to cancer in women, which will aid in the development of interventions for reducing risk for several cancers. ..
  17. Growth Hormones and Breast Cancer Risk
    Shelley S Tworoger; Fiscal Year: 2013
    ..Ultimately, elucidating the role of prolactin in breast cancer could open up multiple new areas of research for both treatment and prevention. ..
  18. Comparative Mechanisms of Cancer Chemoprevention
    Roderick H Dashwood; Fiscal Year: 2013
    ..This application is innovative and timely in bridging basic mechanisms, preclinical models, and human studies of epigenetics and diet. ..
  19. Follow-up of Ovarian Cancer Genetic Association and Interaction Studies (FOCI)
    Thomas A Sellers; Fiscal Year: 2013
    ..g., mucinous and clear cell). ..
  20. Penn TREC Survivor Center
    Kathryn H Schmitz; Fiscal Year: 2013
    ..abstract_text> ..
  21. A MULTILEVEL APPROACH TO ENERGY BALANCE AND CANCER ACROSS THE LIFECOURSE
    Graham A Colditz; Fiscal Year: 2013
    ..To address these aims, we propose four research projects and five cores that form a cohesive, transdisciplinary center focused on research, training/career development, and dissemination. ..