Dynamism: Identifying Key Time Periods for Cancer Control. Susan M Krebs-Smith, PhD, MPH US National Cancer Institute

Transcription

1 Dynamism: Identifying Key Time Periods for Cancer Control Susan M Krebs-Smith, PhD, MPH US National Cancer Institute

2 Outline What is meant by dynamism? Why is it important? What are the key questions? What are some examples?

3 What is meant by dynamism?

4 Dynamism Refers to a process or system characterized by constant change

5 Multi-dimensionality vs dynamism Multidimensional, static diet Dynamism

6 Dynamism Refers to a process or system characterized by constant change Diet fits this criterion Long-term dynamism: over years Short-term dynamism: day-to-day

7 Why is this important?

8 Cancer has a long latency DNA damage to cells Abnormal cell growth Lesion Metastasis Diagnosis Treatment

9 Cellular processes are influenced by diurnal variations Patterson et al., J. Acad. Nutr. Diet., 2015

10 What are the key questions?

11 Long-term Do specific time periods represent heightened risk? In Utero Infancy and Childhood Adolescence Adulthood Older Adulthood

12 Life transitions and diet change Reflects maternal diet Food intake independent of parents Dietary change explored or necessary In Utero Infancy and Childhood Adolescence Adulthood Older Adulthood Breast/formula fed? Food preferences established Partner, children influence food choices

13 Institute of Medicine, Board on Health Care Services, Board on Health Sciences Policy published December 7, 2011 Overall, the IOM finds that major advances have been made in understanding breast cancer and its risk factors, but more needs to be learned about its causes and how to prevent it. The report urges a life-course approach to studying breast cancer because new information suggests that women and girls might be more susceptible to some risk factors during certain life stages.

14 Atomic bomb radiation and breast cancer 10 RR >4 Relative Risk RR < < Tokunaga et al., Radiat. Res., 1994 Age at Radiation Exposure (y)

15 Selected breast cancer risk factors* Risk Factor Comparison RR 95% CI Age at menarche 15 vs. <12 y 0.72 ( ) Parity 3 vs. none 0.72 ( ) Age at first birth >30 vs. 20 y 1.46 ( ) Education >HS vs. <HS 1.08 ( ) BBD Yes vs. No 1.53 ( ) Maternal history Yes vs. No 1.38 ( ) Sister history Yes vs. No 1.47 ( ) *Analysis includes 322,647 women followed for 5-7 years, with 4,827 incident cases of breast cancer. Hunter et al., Cancer Cause. Control, 1997

16 Selected breast cancer risk factors* Risk Factor Comparison RR 95% CI Age at menarche 15 vs. <12 y 0.72 ( ) Parity 3 vs. none 0.72 ( ) Age at first birth >30 vs. 20 y 1.46 ( ) Education >HS vs. <HS 1.08 ( ) BBD Yes vs. No 1.53 ( ) Maternal history Yes vs. No 1.38 ( ) Sister history Yes vs. No 1.47 ( ) *Analysis includes 322,647 women followed for 5-7 years, with 4,827 incident cases of breast cancer. Hunter et al., Cancer Cause. Control, 1997

17 Estrogen levels throughout life pregnancy Estrogen levels, pg/ml birth OC use menopause HRT puberty Age, years Kushi, Workshop: Extending Methods in Dietary Patterns Research, 2016 Most breast cancer studies

18 Risk of early puberty by infant feeding practice* 1.2 Formula fed Mixed fed Breastfed Hazard Ratio Thelarche Pubarche *BCERP studies Kale et al., Matern Child Hlth. J., 2015

19 Long-term Does risk or benefit accumulate over time? In Utero Infancy and Childhood Adolescence Adulthood Older Adulthood

20 Uauy and Solomons, J Nutr., 2005

21 Long-term Does a change in diet alter the course of the risk profile? Healthy diet In Utero Infancy and Childhood Unhealthy diet Adolescence Adulthood Older Adulthood

22 Mozaffarian et al., N. Engl. J. Med., 2011.

23 Short-term What are the patterns of eating frequency? 6 am Noon 6 pm

24 Examples of eating frequency patterns Mattson et al., P. Natl. Acad. Sci. USA, 2014

25 Short-term If we alter eating frequency, does it modify the biology?

26 Short-term metabolic effects Patterson et al., J. Acad. Nutr. Diet., 2015

27 Figure 2 Downstream effects on health Patterson et al., J. Acad. Nutr. Diet., 2015

28 What are some examples?

29 Carbohydrate intake and breast cancer Postmenopausal women* Glycemic index (p trend=0.02) Fiber (p trend=0.35) Total CHO (p trend=0.82) Relative Risk (low) (high) *Nurses Health Study, Carbohydrate intake (quintiles) Holmes et al., Am. J. Epidemiol., 2004

30 Carbohydrate intake and breast cancer Adolescent girls* Glycemic index (p trend=0.01) Fiber (p trend=0.11) Total CHO (p trend=0.59) Relative Risk (low) (high) *Nurses Health Study II, Frazier et al., Cancer Cause. Control, 2004 Carbohydrate intake (quintiles)

31 Risk of pancreatic cancer by alcohol dose, duration, and pattern of consumption, in men Highest lifetime alcohol consumption conferred > twofold increased risk which was elevated regardless of when in the past the heavy consumption occurred increased with increasing decades of heavy consumption History of binge drinking increased risk regardless of when binging first occurred most dramatically for those whose last episode occurred 6-10 years before diagnosis (6-fold increase) and years duration was positively associated with risk Gupta et al., Cancer Cause. Control, 2010

32 Mortality in male Seventh-day Adventists, by age at entry to church and duration of membership MRR 2.46 Mortality rate by age at entry, relative to those <20 y Mortality rate by duration in church, for those entering at different age decades Age Heuch et al., J. Clin. Epidemiol., 2005

33 Frequency and circadian timing of eating may influence biomarkers of inflammation 40 4 % change in kcal consumed in evening % increase in kcal/d resulted in ~3% increase in CRP change in # meals/snacks consumed in day One more meal/d resulted in ~8% lower CRP % change in CRP -4 % change in CRP Marinac et al., PLOS ONE, 2015

34 Frequency and circadian timing of eating may influence biomarkers of inflammation Systemic inflammation 4 may be lowered by 3 eating more frequently change in # hours nighttime fasting An increase of 1 hour in fasting duration resulted in ~8% lower CRP, but only among women who ate <30% of kcal in evening reducing evening energy intake fasting for longer nightly intervals This may reduce breast cancer risk in the long run -4 % change in CRP Marinac et al., PLOS ONE, 2015

35 Summary Diets are dynamic in both the short-term and longterm Patterns of long- and short-term dynamism may be critical to cancer control There are many questions worth exploring in this area

36 Acknowledgements Jill Reedy Angela Liese Stephanie George Larry Kushi Jennifer Lerman Marian Neuhouser