Fred Tabung, PhD(c), MSPH Department of Epidemiology and Biostatistics Cancer Prevention and Control Program Arnold School of Public Health, USC 4 th Annual USC Center for Research in Nutrition and Health Disparities, Annual Symposium March 21, 2014

CANCER PREVENTION & CONTROL PROGRAM  Literature-derived population-based index to assess the inflammatory potential of diet  Developed from published associations of 45 dietary factors (macronutrients, micronutrients and foods) and six inflammatory biomarkers  Assesses the inflammatory potential of an individual’s diet on a continuum from maximally anti- inflammatory to maximally pro-inflammatory  Validated using data on hsCRP and 24-hour dietary recall interviews (24HR) and 7-day dietary recalls (7DDR)

CANCER PREVENTION & CONTROL PROGRAM  Shivappa N, Steck SE, Hurley TG, Hussey JR, Hebert JR. Designing and Developing a Literature-derived, Population- based Dietary Inflammatory Index. Public Health Nutr 2013; S [pii]; /S [doi]:1-8.  Shivappa N, Steck SE, Hurley TG, Hussey JR, Ma Y, Ockene IS, Tabung FK, Hebert JR. A Population-based Dietary Inflammatory Index Predicts Levels of C-Reactive Protein in the Seasonal Variation of Blood Cholesterol Study (SEASONS). Public Health Nutr 2013; S [pii]; /S [doi]:1-9.

CANCER PREVENTION & CONTROL PROGRAM Food group (medium servings/day) Q1 (-7.055, < ) (healthiest) Q2 (-3.136, <-1.995) Q3 (-1.995, < ) Q4 (-0.300, <1.953) Q5 (1.953, 5.636) (least healthy) Fruits Vegetables Combo Fruit/Veg Fish 0.07 Red meat Poultry Soy Nuts Combo Nut/soy Grains Whole Grain Milk Dairy Actual intake data in the WHI CT-OS

CANCER PREVENTION & CONTROL PROGRAM  About 65,000 American women are projected to be diagnosed with colorectal cancer (CRC) in 2014  3 rd most commonly diagnosed cancer in women after breast and lung cancers  Adherence to dietary patterns such as DASH, HEI and Med diet, has been shown to be associated with reduced CRC risk  Evidence of an influence of inflammation on CRC:  Patients with ulcerative colitis and Crohn's disease have an increased risk of developing CRC  Reduced risk of colon cancer with use of aspirin or other NSAIDs

CANCER PREVENTION & CONTROL PROGRAM  To utilize the DII to evaluate the association of the inflammatory potential of diet with risk of colorectal cancer in postmenopausal women

CANCER PREVENTION & CONTROL PROGRAM  DII calculated from baseline FFQs ( )  Both OS and CT data used  Categorized into quintiles  Participants followed until incident colorectal cancer or September 30, 2010  Colorectal cancer cases ascertained through a centralized physician adjudication process (n=1,922)

CANCER PREVENTION & CONTROL PROGRAM  Excluded from analysis: ◦ Women who reported previous CRC at baseline or missing previous CRC status at baseline ◦ Women with implausible reported total energy intake values (≤600 kcal/d or ≥ 5000 kcal/d) or extreme body mass index (BMI) values (≤15kg/m 2 or ≥ 50kg/m 2 )  Multiple covariate-adjusted Cox proportional hazards (PH) regression models used to calculate hazard ratios (HR) for: ◦ colorectal cancer ◦ colon cancer  proximal colon cancer  distal colon cancer ◦ rectal cancer

CANCER PREVENTION & CONTROL PROGRAM  Lowest DII quintile (most anti-inflammatory diet) was the referent for all models  Potential effect modification by waist-to-hip ratio, waist circumference, BMI, and NSAID use, investigated by stratifying on these covariates in the Cox PH models  Tests of linear trend adjusted for covariates, computed by assigning the median value of each quintile to each participant in the quintile  Sensitivity analyses- exclusion of CRC cases that occurred within 3 years from baseline  Analyses by stage of CRC at diagnosis (localized, regional and distant)

CANCER PREVENTION & CONTROL PROGRAM  Total energy intake  Age  BMI  Race/ethnicity  Educational level  Physical activity  Family history of colorectal cancer  Diabetes  Hypertension  Arthritis  History of colonoscopy  History of occult blood tests  NSAID use  Category & duration of estrogen use  Category & duration of combined estrogen & progesterone use  DM arm, HRT arm, and CaD arm

CANCER PREVENTION & CONTROL PROGRAM Risk of colorectal cancer across quintiles of the DII Q1 (-7.055, < ) (healthiest) Q3 (-1.995, < ) Q5 (1.953, 5.636) (least healthy) ReferentHR (95%CI) P trend Colorectal cancer (0.84, 1.14)1.22 (1.05, 1.43)0.02 Colorectal cancer cases, (19.0%)360 (18.7%)435 (22.6%) Colon cancer (0.83, 1.15)1.23 (1.03, 1.47)0.02 Colon cancer cases, (19.2%)289 (18.5%)346 (22.2%) Proximal colon (0.79, 1.20)1.35 (1.09, 1.67)0.01 Proximal colon cancer cases, (18.7%)181 (17.5%)229 (22.2%)

CANCER PREVENTION & CONTROL PROGRAM  HRs were strengthened when CRC cases that developed within 3 years from baseline were excluded, ◦ e.g. HR Q5vsQ1 for colon cancer: 1.36 (1.11, 1.66), P trend =0.003  HRs for CRC differed by category of NSAID use: ◦ P interaction =0.26 ◦ Non-NSAID users: 1.31 (1.05, 1.65) Q5vsQ1, P trend =0.03 ◦ NSAID users: 1.11 (0.89, 1.38) Q5vsQ1, P trend =0.61  No significant association with: ◦ Distal colon cancer ◦ Rectal cancer ◦ CRC stage at diagnosis

CANCER PREVENTION & CONTROL PROGRAM  Study limited to postmenopausal women  FFQ measurement error  Diet assessment at only one time point

CANCER PREVENTION & CONTROL PROGRAM  Consumption of pro-inflammatory diets increases the risk of colorectal cancer in older women, especially colon cancer located in the proximal colon  Consumption of pro-inflammatory diets increases the risk of colorectal cancer in older women not regularly taking NSAIDs

CANCER PREVENTION & CONTROL PROGRAM Longitudinal Changes in Diet-related Inflammation and Risk of Cancer in Women  An assessment of the inflammatory potential of diet over time in the Women’s Health Initiative  Changes in the DII over time and risk of colorectal cancer in women

CANCER PREVENTION & CONTROL PROGRAM Chair:  Susan E. SteckUSC Dept. of EPID/BIOS and Cancer Prevention and Control Program Members :  Yunsheng Ma UMass Medical School  Angela D. Liese USC Dept. of EPID/BIOS and Center for Nutrition & Health Disparities  Jiajia ZhangUSC Dept. of Epidemiology & Biostatistics  James R. Hebert USC Dept. of EPID/BIOS and Cancer Prevention and Control Program

CANCER PREVENTION & CONTROL PROGRAM  Lifang Hou Northwestern Univ. Feinberg School of Medicine  Bette CaanKaiser Permanente Division of Research  Karen K. JohnsonUniv. of Tennessee Health Science Center  Yasmin Mossavar-RahmaniAlbert Einstein College of Medicine  Jean Wactawski-WendeSUNY Dept. of Social and Preventive Medicine  Judith K. Ockene UMass Medical School  Nitin Shivappa USC Dept. of EPID/BIOS and Cancer Prevention and Control Program

CANCER PREVENTION & CONTROL PROGRAM  Mr. Tabung was supported by an NIH F31 National Research Service Predoctoral Award, a USC SPARC grant and a fellowship from the USC Center for Colon Cancer Research  Drs. Steck and Zhang were supported by the Prevent Cancer Foundation - Living in Pink grant  Dr. Hébert was supported by an Established Investigator Award in Cancer Prevention and Control from the Cancer Training Branch of the National Cancer Institute (K05 CA136975).  Funding for DII development was provided by the CPCP  The WHI program is funded by the National Heart, Lung, and Blood Institute, National Institutes of Health, U.S. Department of Health and Human Services through contracts HHSN C, HHSN C, HHSN C, HHSN C, HHSN C, and HHSN C.