diet, obesity, lifestyle and cancer prevention: epidemiologic perspectives

Diet, obesity, lifestyle and cancer prevention:

Epidemiologic perspectivesGraham A Colditz, MD DrPH

Niess-Gain ProfessorChief, Division of Public Health Sciences

November, 2017

Department of SurgeryDivision of Public Health Sciences

OutlineReview evidence on contribution of diet, obesity, lifestyle and in particualr, increasing burden of obesity on cancerIdentify:

IssuesGaps in knowledgeOpportunities


Lifestyle: high income countriesCause

% cancer caused

Magnitude possible

reductionTime (yrs)

Smoking 33Overweight/obesity 20Diet 5Lack of exercise 5Occupation 5Viruses 5-7Family history 5Alcohol 3UV/ionizing radiation 2

Reproductive 3Pollution 2 Colditz et al, Sci Transl Med 2012



% cancer caused

Magnitude possible

reductionTime (yrs)

Smoking 33 75%Overweight/obesity 20 50%Diet 5 50%Lack of exercise 5 85%Occupation 5 50%Viruses 5-7 100%Family history 5 50%Alcohol 3 50%UV/ionizing radiation 2 50%

Reproductive 3 0Pollution 2 0



% cancer caused

Magnitude possible

reductionTime (yrs)

Smoking 33 75% 10-20Overweight/obesity 20 50% 2-20Diet 5 50% 5-20Lack of exercise 5 85% 5-20Occupation 5 50% 20-40Viruses 5-7 100% 20-40Family history 5 50% 2-10Alcohol 3 50% 5-20UV/ionizing radiation 2 50% 2-10

Reproductive 3 0 N/APollution 2 0 N/A


Time course: lung & total mortalityCurrent smoker:continuing


Medical interventions proven to prevent cancer: high-income

InterventionTarget Magnitude of

reduction Time (yrs)

Aspirin Colon mortality 40% 20+SERMs Breast incidence 40-50% 5+Salpingooophorectomy Familial breast cancer 50% 3+

Screening for colorectal cancer Colon cancer mortality 30-40% 10

Viruses - HPV Cervical cancer incidence 50-100% 20+- Hep B Liver cancer incidence 70-100% 20+

Mammography Breast cancer mortality 30% 10-20Serial CT lung Lung cancer mortality 20% 6+

Colditz et al, Sci Transl Med 2012


Histologically confirmed cervical abnormalities, Vic, Australia

CIN2, CIN3

Brotherton et al MJA 2016


Pancreatic cancer

Yachida Nature 2010; Luebeck EG. Nature 2010


Summary of evidence: Adolescent exposures relation to risk of BBD and breast cancer

Lifestyle Relative Risk BBD Breast Cancer (premenopausal)

Alcohol

Peak Growth Velocity

Height

Nuts

Fiber

Carotenoids Fruit and veggies

Vegetable protein

Family history

Physical activityColditz Bohlke Berkey Br Ca Res Treat 2015, Colditz & Bohlke 2014


Alcohol intake, ages 18-22, incident proliferative BBD

Alcohol intake(grams/day)

Cases

(678)

Person-year

RR (95% CI)

None 155 64,827 1.0 reference0.1-4.9 193 78,365 1.11 (0.89, 1.38)5.0-14.9 236 88,310 1.36 (1.09, 1.69)>15 30 9519 1.35 (1.01, 1.81)

p, trend <0.01

Liu et al. – Pediatrics, 2012


Alcohol before first pregnancy, NHSII

Liu, Colditz, Tamimi JNCI 2013


Adolescent fiber & proliferative BBD: NHSII

Su et al. Cancer Causes Control 2010


Are we there yet?


Obesity and cancer, time line -• 1990s WHO, US Dietary Guidelines, adopt

common cut points• 2002 IARC report• 2008 et seq WCRF report• 2016 update of IARC report


IARC 2002 and Calle 2003• Review of evidence on weight obesity and

physical activity in relation to cancer• Calle: ACS cohort published after the

IARC review panel


IARC 2002“Sufficient evidence in humans for cancer-preventive effect of avoidance of weight gain for cancers of the colon, esophagus (adenocarcinoma), kidney (renal cell), breast (postmenopausal), and corpus uteri”

Translate: Obesity causes cancerIACR Handbooks of Cancer Prevention Vol 6, 2002


Review of Evidence, IARC 2002Obesity

LevelofEvidence

RiskIncreaseAssociatedwithObesity

Small

(RR1.09-1.34)Moderate

(RR1.35-1.99)Large

(RR2.0-4.9)VeryLarge(RR5.0+)

Convincing Colon Breast Esophagus Uterus Kidney Probable


Calle et al 2003


Workgroup reviewed measures of adiposity; animal models; mechanisms; and epidemiologic evidence.Concluded lack of body fatness lowers risk, or obesity causes cancer.

NEJM August 25, 2016


Evidence evolvingFrom only a couple of prospective cohorts in 2002, adding ACS mortality in 2003• Now evidence from 30 to 50 or more

prospective cohorts • Pooled analysis of individual participant

data from studies addressing BMI and less common cancers


Why prospective studies and pooled data• Measure adiposity and risk of subsequent

cancer• Avoid weight change due to disease


Individual participant data –pooled analysisIPD meta-analyses can improve the quality of data and the type of analyses that can be done and produce more reliable results (Stewart and Tierney 2002). For this reason they are considered to be a ‘gold standard’ of systematic review. In fact, IPD meta-analyses have produced definitive answers to clinical questions, which might not have been obtained from summary data.

Cochrane Handbook Ch 18 and IPD methods


GI• Gastric cardia• Liver• Pancreas• Gall bladder


PancreasMore than 20 prospective studies and case-control studies indicating a positive dose-response relation. Observed in the large majority of studies and in both genders. Compared to normal weigh, the RR for overweight was 1.18 (1.03-1.36) and for obesity 1.47 (1.23-1.75), estimated from pooled analysis of 14 cohorts [Genkinger 2011].


Genkinhger et al 2011

2135 casesDuring 846,340 py

Forest plot of RR for BMI >30 vs 21-22.9

Baseline BMI


BMI in early adulthood


Relative risk of ovarian cancer by BMI and HT use

Collaborative Group on Epidemiological Studies of Ovarian Cancer (2012) Ovarian Cancer and Body Size: Individual Participant Meta-Analysis Including 25,157 Women with Ovarian Cancer from 47 Epidemiological Studies. PLoS Med 9(4): e1001200. doi:10.1371/journal.pmed.1001200http://journals.plos.org/plosmedicine/article?id=info:doi/10.1371/journal.pmed.1001200

Never use HT

Ever use


Evidence, 2016

RiskIncreaseAssociatedwithObesity LevelofEvidence

Small(RR1.09-1.34)

Moderate(RR1.35-1.99)

Large(RR2.0-4.9)

VeryLarge(RR5.0+)

Convincing Ovary Colon Breast Esophagus Thyroid Gastriccardia

LiverKidney Uterus

Gallbladder Pancreas

MeningiomaMultiplemyeloma

Probable Malebreast

Fatalprost.DiffuseLargeB-celllymphoma


Time course obesity

Increase in childhood adiposity


Pancreatic cancer US incidence 1992 to

2014

Age 20 to 49

Rising incidence 0.9% per year (significant)


Colorectal cancer US incidence 1992 to

2014

Age 20 to 49

Rising incidence 1.7% per year (significant)


Childhood and early adult adiposity• Often consistent with adult adiposity and

risk• Analysis not always clear

• Methods, correlated variables, and interpretation

• Challenges in breast cancer• Inverse relation with adiposity at ages 5, 10, before menarche• Weight gain increases risk• How does childhood adiposity reduce risk for life?


0 10 18 30 47 Age (years)

Premenopausal Postmenopausal

50

+kg

Post-menopausal Breast Cancer Risk

-1 0.80 0.98

1.36 (weight change from 18 to attained)

Adiposity

1.37 (weight change after menopausal to attained)

Reference: Rosner, B., Eliassen, A. H., Toriola, A. T., Chen, W. Y., Hankinson, S. E., Willett, W. C., ... & Colditz, G. A. (2017). Weight and weight changes in early adulthood and later breast cancer risk. International journal of cancer, 140(9), 2003-2014.

+kg+kg

Age (years)

-1

Pre-menopausal Breast Cancer Risk

0.66 0.741.0


0 10 18 30 47 Age (years)

Premenopausal Postmenopausal

50

+kg

Post-menopausal Breast Cancer Risk

-1 0.80 0.98

1.36 1.36 (weight change from 18 to attained)

Adiposity

1.37 (weight change after menopausal to attained)

Reference: Rosner, B., Eliassen, A. H., Toriola, A. T., Chen, W. Y., Hankinson, S. E., Willett, W. C., ... & Colditz, G. A. (2017). Weight and weight changes in early adulthood and later breast cancer risk. International journal of cancer, 140(9), 2003-2014.

+kg+kg

Age (years)

-1

Pre-menopausal Breast Cancer Risk 0.66 0.74 1.0

ER-/PR-Breast Cancer RiskRR / 30kg

0.73 (0.55-0.98)

0.70(0.46-1.05) Weight change unrelated to risk


Top priorities to advance the science –obesity and cancerImproved (consistent) approaches to modeling weight gain across life course and cancer riskQuantify benefits of weight lossMeasures of adiposity• Do we have it right, do measures vary by

age; race/ethnicity; region of the world


Top priorities to advance the science – diet, lifestyle and cancerImproved (consistent) approaches to modeling exposure in time course of cancer developmentMeasures of diet lifestyle in childhood adolescence • Can biomarkers in blood banks replace

recall of childhood adolescent exposures?


Behavioral, Social, and Policy interventions that impact Cancer PreventionIntervention Target Type of Ix Evidence

review

Reduce tobacco use

Children and Adolescents

Smokers to quit

Combined Pharmaco/behavioral IxsSmoke-free policiesTobacco taxes

Surgeon General

Increase physical activity

Individuals and community norms

Urban designStairs and workplace

Surgeon General

Reduce Obesity Population School & work environmentPhysical activityFood & beverage

IOM report 2012

Limit alcohol intake Population Taxes WHO

Reduce UV exp Children, AYA All of above WHO


Wall-eCaptain

Will we all have access to driverless cars?

What will our cancer risk be?

diet, obesity, lifestyle and cancer prevention: epidemiologic perspectives

Health & Medicine