Intake of Dairy Products in Relation to Risk and Survival of - PowerPoint PPT Presentation

Intake of Dairy Products in Relation to Risk and Survival of Prostate Cancer — A 28-year follow-up study Yan Song, MD, MS Channing Network Medicine, Brigham & Women’s Hospital and Harvard Medical School Department of Epidemiology, UCLA Fielding School of Public Health

Prostate(cancer(incidence,(mortality,(and(survivorship(in(US( 100% 81% 80% Stage 60% 40% 12% 20% 3% 0% Localized Regional Distant Stage at Diagnosis 100% 100% 100% 5-year Survival 80% 60% 40% 27.80% 20% 0% Localized Regional Distant Stage at Diagnosis Siegel et al. CA Cancer J Clin 2011 Data from seer.cancer.gov !

A(meta8analysis(of(the(associa:on(of(dairy(food( intakes(with(risk(of(incident(prostate(cancer( Meta-analysis #1 Meta-analysis #2 Cohort studies: RR=1.06, 95% CI: 0.91, 1.23 Case-control studies: RR=1.14, 95% CI: 1.00, 1.29 Limitations : RR=1.11, 95% CI: 1.00, 1.22 ! Few evaluated different types of dairy foods with risk of prostate cancer ! Few considered advanced disease or Gao et al. JNCI 2005 prostate cancer-specific death as a major outcome

The Physicians’ Health Study (PHS) heart disease and cancer – 22,071 US male physicians, aged 40 to 84 in 1982 • Dietary assessment at enrollment, run-in, and 12-mo questionnaires • Ascertainment of incident PCa and PCa mortality • • Used Cox proportional hazards regression models Used Cox proportional hazards regression models

RR of incident prostate cancer by intake of dairy food, PHS 1.5 P-trend = 0.003 1.4 1.3 1.2 Relative risk 1.14 (0.99-1.31) 1.1 ref ! 1.0 0.9 0.8 0.7 0.6 <0.5 0.5 to 1.0 1.0 to 1.5 1.5 to 2.5 ≥ 2.5 All dairy food intake (servings/d)

RR of incident prostate cancer by intake of whole milk and skim/low-fat milk, PHS 1.5 Whole(milk( 1.4 Skim/low8fat(milk( 1.3 1.22 (1.10-1.36) Relative risk 1.2 1.1 ref ! 1.0 0.98 (0.84-1.13) 0.9 0.8 0.7 0.6 Rarely ≤ 1 serving/wk 2 to 6 servings/wk ≥ 1 serving/d Dairy food intake (servings/d) *Covariates adjusted: age, cigarette smoking, vigorous exercise, alcohol, race/ethnicity, BMI, baseline diabetes status, red meat consumption, and mutually adjusted for intake levels of each other.

RR of incident prostate cancer by intake of whole milk and skim/low-fat milk and Stratified by subtypes of disease, PHS Whole milk Skim/low-fat milk PCa subtypes 1.19 (0.86-1.63) High-grade 0.78 (0.50-1.22) Low-grade * ! 0.94 (0.79-1.04) 1.24 (1.10-1.40) Advanced 1.01 (0.71-1.46) 0.85 (0.52-1.41) Localized 1.22 (1.08-1.38) * ! 0.92 (0.77-1.10) Fatal * ! 1.47 (0.98-2.21) 1.03 (0.72-1.47) 0.1 1 10 0.1 1 10 *High-grade (n = 317): Gleason > 7; Low-grade (n = 2105): Gleason ≤ 7; Advanced (n = 272): T3/T4/N1/M1; Localized (n = 2016): T1/T2; Fatal (n = 305): died of prostate cancer.

Risk of prostate cancer-specific mortality by pre-diagnostic intake of whole milk and skim/low-fat milk in prostate cancer cases, PHS 3.4 Whole milk 2.8 Skim/low-fat milk Hazard ratio 2.2 2.03 (1.28-3.22) 1.6 1.0 0.97 (0.65-1.45) 0.4 Rarely ≤ 1 serving/wk 2 to 6 servings/ ≥ 1 serving/d wk Dairy food intake (servings/d) *Covariates adjusted: age, cigarette smoking, vigorous exercise, alcohol, race/ethnicity, BMI, baseline diabetes status, red meat consumption, Gleason score, stage of tumor, and mutually adjusted for intake levels of each other.

Conclusions • Dairy product intake was associated with PCa risk. • Skim/low-fat milk intake was associated with PCa risk, primarily with low-grade and early stage tumors. • Whole milk intake was associated with fatal PCa risk and fatality after diagnosis.

Acknowledgement ! Jing Ma Funding support This!project!has!been!funded!by! – Jorge E. Chavarro CA42182,!CA141298,!CA131945,! Yin Cao CA097193,!the!Transdisciplinary! Weiliang Qiu Research!in!EnergeDcs!and!Cancer! Center!(TREC)!U54CA155626!from!the! Lorelei Mucci NaDonal!InsDtutes!of!Health,!and!the! Howard D. Sesso NaDonal!Cancer!InsDtute!of!Canada! (019894).!! Meir J. Stampfer Yan!Song!is!also!supported!by!the!UCLA! – Edward Giovannucci Burroughs!Wellcome!Fund!InterTschool! Michael Pollak Training!Program!in!Metabolic!Diseases! (BWFTITTMD).! Simin Liu

HR of prostate cancer death by pre-diagnostic intake of dairy product and dairy calcium in prostate cancer cases, PHS 3.4 3.4 2.8 2.8 Hazard ratio Hazard ratio 2.2 2.2 1.6 1.6 1.0 1.0 0.4 0.4 <0.5 0.5 to 1.0 1.0 to 1.5 1.5 to 2.5 ≥ 2.5 Q1 Q2 Q3 Q4 Q5 All dairy food intake (servings/d) Calcium from dairy food (g/d) HR=1.40, 95% CI: 0.78, 2.51 HR=1.47, 95% CI: 0.96, 2.25 (Highest vs. lowest group) (Q5 vs. Q1)

Table 1. Baseline characteristics by category of baseline dairy product intake ( n = 21,660) Dairy products a Whole milk Skim/low-fat milk <0.5 ≥ 2.5 ≤ 1/wk ≥ 2/wk ≤ 1/wk ≥ 2/wk Age (y) 52.3 55.1 53.0 55.5 53.4 53.6 BMI (%) Normal 56 56 58 56 57 59 Overweight 40 35 38 39 39 37 Obese 4 9 4 4 4 4 White (%) 85 96 93 89 90 95 Diabetes (%) 1.6 2.6 1.7 2.6 1.6 2.3 a Based on the consumption of five major dairy foods (whole milk, skim/low-fat milk, hard cheese, ice cream, and cold breakfast cereal), assessed in 1982 to 1984.

Table 1. Baseline characteristics by category of baseline dairy product intake ( n = 21,660) Dairy product a Whole milk Skim/low-fat milk <0.5 ≥ 2.5 ≤ 1/wk ≥ 2/wk ≤ 1/wk ≥ 2/wk Smoking (%) Never 46 61 51 48 48 54 Former 41 35 40 37 41 37 Current 13 4 9 15 12 8 Alcohol (%) b 29 20 24 24 26 21 Exercise (%) c 48 59 55 50 51 58 Red meat 0.6 0.8 0.7 0.8 0.7 0.7 (srv/wk) a Based on the consumption of five major dairy foods (whole milk, skim/low-fat milk, hard cheese, ice cream, and cold breakfast cereal), assessed in 1982 to 1984. b Frequent drinker is defined as people who drink alcoholic beverages every day. c Vigorous exercise is defined as to exercise vigorously to a sweat more than twice per week.

1.5 1.4 1.3 * ! 1.2 Relative risk * ! Whole milk 1.1 Skim/low-fat milk 1.0 Hard cheese Ice cream 0.9 Cold cereal 0.8 0.7 0.6 Rarely ≤ 1 serving/wk 2 to 6 servings/wk ≥ 1 serving/d All dairy food intake (servings/d) Figure 2. Relative risk estimates for prostate cancer by intake of different dairy products in PHS

Whole milk Skim/low-fat milk 0.78 (0.50-1.22) 1.19 (0.86-1.63) High-grade 0.94 (0.79-1.04) * ! 1.24 (1.10-1.40) Low-grade 0.85 (0.52-1.41) 1.01 (0.71-1.46) Advanced 0.92 (0.77-1.10) 1.22 (1.08-1.38) Localized * ! 1.47 (0.98-2.21) 1.03 (0.72-1.47) Fatal * ! 1.41 (0.91-2.17) 1.47 (1.02-2.13) Pre-PSA 1.45 (0.87-2.40) 1.34 (0.89-2.02) Post-PSA (symptom) 0.77 (0.60-0.98) 1.27 (1.09-1.49) Post-PSA (screening) * ! * ! 0.1 1 10 0.1 1 10 Figure 3. Multivariate relative risk estimates for categories of prostate cancer cases by intake of dairy product in PHS

Difference!between!whole!milk!and!skim!milk ! Nutrient( Unit( Whole/Skim( Difference(in(8(oz.( %(of(DRI( Total!fat! g! 41:1! 7.2! 11%! SFA! g! 37:1! 4.1! 20%! MUFA! g! 39:1! 1.8! n/a! PUFA! g! 65:1! 0.4! n/a! Cholesterol! mg! 5:1! 18.1! 6%! Vitamin!A! IU! 11:1! 332! 7%! Vitamin!D! IU! >100:1! 4.5! 1%! Vitamin!E! mg! 7:1! 0.1! 0.9%! Vitamin!K! >100:1! 0.7! 0.6%! µg! Se! µg! 1.2:1! 1.4! 2%! Cu! mg! 2:1! 0.03! 3%! Zn! mg! 1:1.1! 0.1! 1%! P! mg! 1:1.2! 38.4! 5%! K! mg! 1:1.2! 54.2! 1%! Betaine! mg! 1:3! 2.9! n/a!