Multiple myeloma (MM) poses a substantial public health, personal and financial burden. Novel therapies have enabled notable gains in MM survival in the past decade, but current United States 5- and 10-year relative survival rates show that MM remains lethal in most patients. Present understanding of MM etiology is inadequate to formulate risk stratification or prevention strategies. Even less is known regarding modifiable factors that could influence MM survival. The identification of lifestyle-based or other relatively inexpensive, accessible approaches to prolonging MM patient survival would further expand the tools available to clinicians and their patients. Inflammation and growth factor dysregulation contribute to MM pathogenesis, and thus it is plausible that potentially modifiable factors that modulate inflammatory or growth factor signaling may influence MM survival. The studies we propose in this application will examine three such plausible factors in the Nurses' Health Study (NHS) and Health Professionals Follow-up Study (HPFS) cohorts: diet quality (as captured by predefined, validated diet patterns), regular aspirin use and body mass index (BMI). Diet patterns have not, to our knowledge, been evaluated in relation to MM risk or survival. We previously observed a 39% reduction in MM risk in participants with higher quantity or duration of regular aspirin use and a 50% increased risk of MM in obese persons in the NHS and HPFS. Aspirin merits evaluation as a potential inexpensive complement to major treatment regimens to further improve MM survival in patients who can tolerate its use. The relation of obesity to MM survival also warrants clarification; usual adult obesity is positively associated with MM risk, bu obesity at MM diagnosis appears to confer a favorable prognosis, and short-term pre-diagnosis weight loss appears to be a better predictor of MM survival than BMI. With >25 years of follow-up and biennially updated, detailed information on these exposures and relevant covariates, and with projected sample sizes for the proposed studies of at least 400 MM patients (330 deaths), we are uniquely equipped in the NHS and HPFS to rigorously evaluate these potential predictors of MM risk and patient mortality. To address our limitation of incomplete clinical data on the MM patients, we also propose exploratory analyses of available clinical data, to aid the interpretation of the primary analyses and assess whether available variables (age, sex and calendar period, or a short survival time) may serve as a reasonable proxy when treatment or disease stage information is not available. These proposed studies will establish the first analyses of MM survival in the NHS and HPFS and guide the development and design of additional survival studies, including in large consortia where the project team has been instrumental in initiating pooled prospective studies on MM. As such, the proposed activities have strong potential to yield valuable insights for MM patients, clinicians and other investigators of MM and thus are likely to have high translational value over both the short- and longer-term to further diminish the burden of MM.

Public Health Relevance

Multiple myeloma (MM) poses a substantial public health, personal and financial burden; improved new therapies had lengthened MM patient survival, but treatment is expensive and the condition is still fatal in the majority of patients. Therefore in this application we propose to establish the irst studies of diet quality, regular aspirin use and obesity (all of which are potentially modifiable factors) and MM patient survival in the Nurses' Health Study and Health Professionals Follow-up Study populations, where we can examine both pre- and post-diagnosis habits or body size. The project will also build capacity for longer-term research on MM survival in these cohort populations and motivate larger collaborative studies of MM across several large study populations affiliated with the National Cancer Institute Cohort Consortium, all of which are likel to offer valuable insights to clinicians and MM patients on the influence of lifestyle on MM survival. Page 1

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Exploratory/Developmental Grants (R21)
Project #
5R21CA198239-02
Application #
9134664
Study Section
Special Emphasis Panel (ZCA1)
Program Officer
Elena, Joanne W
Project Start
2015-09-01
Project End
2017-08-31
Budget Start
2016-09-01
Budget End
2017-08-31
Support Year
2
Fiscal Year
2016
Total Cost
Indirect Cost
Name
Brigham and Women's Hospital
Department
Type
DUNS #
030811269
City
Boston
State
MA
Country
United States
Zip Code
Birmann, Brenda M; Andreotti, Gabriella; De Roos, Anneclaire J et al. (2017) Young Adult and Usual Adult Body Mass Index and Multiple Myeloma Risk: A Pooled Analysis in the International Multiple Myeloma Consortium (IMMC). Cancer Epidemiol Biomarkers Prev 26:876-885
Santo, Loredana; Teras, Lauren R; Giles, Graham G et al. (2017) Circulating resistin levels and risk of multiple myeloma in three prospective cohorts. Br J Cancer 117:1241-1245