Dietary Patterns and Cancer Risk Chandrika Piyathilake, BDS, MPH, PhD University of Alabama at Birmi

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Dietary Patterns and Cancer RiskChandrika
Piyathilake, BDS, MPH, PhDUniversity of Alabama
at Birmingham
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Diet-Cancer Association
The importance of diet was emphasized more than a
quarter century ago 35 (10-70) of all
cancers in the United States might be
attributable to dietary factors 90 of
colorectal cancer in the United States may
be preventable through dietary
modifications Doll and Peto, J. Natl. Cancer
Inst. 1981, 66, 1191-1308.
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Data from 1981-2007

• Not always consistent
• Most consistent results

Risk of cancer
Consumption
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Fruits Vegetables and Cancer Risk

• Strong link between eating fruits and vegetables
  and lower cancer risk
• Recent data from cohort studies - not
  consistently
• shown that a diet rich in fruits and vegetables
  prevents cancer in general

Hung HC, Joshipura KJ, Jiang R, et al. Fruit and
vegetable intake and risk of major chronic
disease. JNCI 2004 96 1577-84
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Reasons for Inconsistency

• Study design issues
• Most studies are cross-sectional
• Making it difficult to conclude whether dietary
  patterns as causing or preventing cancer
• Difficult nature of question
• Complexity in human diet

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Interest in Diet-Cancer Association continues

• Few modifiable risk factors for cancer have been
  identified
• Dietary habits are one of the most important
  modifiable determinants of cancer risk
• Evidence continues to suggest that altering
  dietary habits may be an effective approach for
  reducing cancer risk

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New Approaches Diet-Disease Association
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• Traditional Approach
• - Examine associations between individual
  nutrients or food groups with disease risk
• New Approach
• - Study dietary patterns, or combinations of
  foods and nutrients, in relation to disease risk

More likely to represent the total diet or key
factors of the diet
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Key Reasons for Examining Dietary Patterns

• Humans eat meals with complex combinations of
  nutrients - likely to be interactive or
  synergistic
• Nutrients in a meal are likely to be highly
  correlated - difficult to examine their separate
  effects
• The effect of a single nutrient may be too small
  to detect, but the cumulative effects of multiple
  nutrients included in a dietary pattern may be
  sufficiently large to detect
• Analyses of a large number of nutrients may
  produce statistically significant associations
  simply by chance

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Commonly Applied Methods to Identify Dietary
Patterns

• Data-driven methods
• - Factor and cluster analysis
• Investigator-driven methods
• - Indices and scores
• Methods combining the two
• - Reduced rank regression

150 Food Items 2-4 Major Dietary
Patterns
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Issues with Dietary Pattern Methods

• No one method of dietary pattern analysis is
  regarded as better than the others
• No consensus on which approach should be used for
  any given disease
• The reproducibility and validity of dietary
  patterns may depend on the nature of the diet
  assessment measure
• Decisions made by researchers during the analysis
  dietary patterns could be subjective
• Need to pay more attention to
  methodological issues

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Dietary Patterns in United States Derived by
Factor Analysis

• Two primary patterns
• First pattern characterized by intake of
  vegetables, fruit, whole grains, low-fat dairy
  products, fish, poultry, and wine (Prudent)
• Second pattern characterized by intake of red
  meats, refined grains, fat, sweets, and alcohol
  (Western)

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Colon Cancer

• Western or prudent
• Western pattern Risk
• Prudent pattern Risk
• Western pattern Risk
• Prudent pattern NS inverse association

Am J Epidemiol. 19981484-16
Int J Cancer. 2005115790-798.
Cancer Causes Control. 200415853-862.
Arch Intern Med. 2003163309-314.
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Association of Dietary Patterns with Cancer
Recurrence

• Prudent and western dietary patterns by factor
  analysis
• Western dietary patterns - worse disease-free
  survival from colon cancer
• Prudent dietary pattern - not significantly
  related to patient outcome

JAMA 2007 298 754-64
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Other Dietary Patterns in US-Factor Analysis

• 1) Vegetable-fish/poultry-fruit
• 2) Beef/pork-starch
• 3) Traditional southern (cooked greens, beans and
  legumes, sweet potatoes, cornbread, cabbage,
  fried fish and chicken, and rice)

Risk of invasive breast cancer in
postmenopausal women (Am J Clin Nutr 2005 82
1308-19).
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Endometrial Cancer
Plant-based, western, ethnic, and
phytoestrogen-rich
No association with endometrial
cancer risk (Cancer Causes
Control 2007 18 957-66, case-control study)

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Dietary Patterns and Cancer Risk-Summary

• Reasonable approach
• Need more cohort studies
• Limited data on response to dietary patterns
• Limited data on biomarkers of dietary patterns

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Response to Dietary Components

• Determined by whether food components can reach
  the target tissues and the amount reached is
  adequate to correct adverse modifications in the
  target tissues
• Higher concentrations of food components in blood
  does not necessarily mean that those components
  are reaching target tissues

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Biomarkers of Dietary Patterns

• Biomarkers are fundamental to evaluating who will
  benefit most from specific dietary patterns

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Biomarkers of Diet and Cancer
Evaluate intake of specific foods or dietary
patterns
Predictive, validated and sensitive biomarkers
Changes in biological effects that are linked to
cancer
Effectively predict individual variation in
response to diet
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Association Between Dietary Patterns and
Biomarkers of Cancer
Limited published data

• Western dietary patterns are positively
  correlated with levels of insulin and insulin
  like growth factors
• Insulin and insulin like growth factors -
  associated with enhanced tumor growth
• Western pattern may facilitate progression of
  cancer

Good biomarkers of cancer?
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Other Biomarkers

• Various markers are important in explaining
  diet-cancer association
• DNA repair
• DNA damage
• Cell proliferation/apoptosis
• Discovery-based biomarkers (nutrigenomics,
  proteomics and metabolomics)

These biomarkers are not examined carefully in
relation to dietary patterns
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Other Issues

• The response to dietary patterns may depend on
  individual genetic make up
• Not all individuals may respond identically to a
  given dietary pattern
• Very limited data in this area

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Example Genetic Polymorphisms
Differences in Genetic Make Up

• Genetic polymorphisms are believed to play a role
  in determining the response to foods components
• Highly plausible that polymorphic differences may
  have contributed to the inconsistencies among
  studies of the health effects of dietary
  components

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Genetic Polymorphisms

• Examples
• Individuals with genetic polymorphisms in
  anti-oxidant enzymes who are at increased risk
  for cancer and may benefit most from increased
  fruit and vegetable consumption, not all
  individuals

MnSOD-Cancer Res 2005 65 2498, 504.
Catalase-Cancer Epidemiol Biomarkers Prev 2006
15 1217, 22.
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Future Directions
Diet is a complex behavior often correlated with
non-dietary behaviors and other factors such as
race/ethnicity and obesity

• Dietary patterns ----------------------------
  Cancer

Smoking, alcohol, race, obesity
Obesity is risk a factor for cancer Diet is a
main factor for obesity epidemic
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Obesity

• Inadequate control for obesity
• A major limitation in most previous studies on
  diet and cancer

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Obesity

• Overweight and obesity are conditions of excess
  body weight affecting millions of people
  world-wide
• 54 of U.S. adults are overweight (BMI gt 25) and
  22 are obese (BMI gt 30)
• If this trend persists, the entire U.S. adult
  population is predicted to be overweight within a
  few generations

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Obesity Epidemic

• Many theories have been put forward to explain
  the obesity epidemic and its health consequences
• The dramatic increase in the global prevalence
  of obesity during the past two decades
  underscores the significance of
• - trends in dietary practices
• - sedentary lifestyle
• - rather than genetic determinants

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Diet and Obesity

• Association between diet and obesity is
  controversial
• - Larger portion sizes
• - High-energy-dense foods
• - Total amount of dietary fat
• - Saturated fat rather than total fat
• - Food generating a high glycemic index
• - Simple sugars and trans fats

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• Food selection by the obese tends to be of poor
  nutrient value and high-calorie
• (NHANES national survey)
• Dietary Patterns

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More Studies Needed.
Dietary Patterns
Cancer
Obesity
Ideal Study Design
Biomarker based cohort study of individuals who
are well characterized for exposure to obesogenic
environment and at risk for developing cancer
Diet, physical activity and genetic
predisposition
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Pending R01 5-year Prospective Follow-up Study
Exposure to Obesogenic Environment and
Progression of HPV Infections to Cervical
Neoplasia A Human Model of Carcinogenesis

• 60 Overweight/obese
• 85 physically inactive
• 60 early signs of metabolic syndrome
• Unhealthy dietary patterns

2 Ongoing R01s
Women Exposed to HR-HPV/Abnormal Pap
20 CIN 2
80 CIN 1
CIN 2
Post LEEP Recurrent CIN 2
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What you eat
Questions??? 205-975-5398 piyathic_at_uab.edu
What you do
Who you are