Nutritional Epidemiology of Cancer EPI 242 Cancer Epidemiology

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Nutritional Epidemiology of Cancer EPI 242: Cancer Epidemiology 2009

Nutritional Epidemiology of Cancer EPI 242: Cancer Epidemiology 2009

Nutritional Epidemiology Overview Role of nutritional epidemiology is to: - provide the best possible

Nutritional Epidemiology Overview Role of nutritional epidemiology is to: - provide the best possible scientific evidence to support an understanding of the role of nutrition in the causes and prevention of ill health - ensure that the information upon which public health decisions are made is of the highest quality Focus of the study may be etiological, prevention, intervention

History � Relatively new as a formal area of research � Long history of

History � Relatively new as a formal area of research � Long history of understanding of how foods relate to diseases � 1600; Beri-beri � 1753; Scurvy � 1980; Keshan disease

Consideration of nutrients in balance 1. Excess- western/affluent societies; long latent period; multiple causes;

Consideration of nutrients in balance 1. Excess- western/affluent societies; long latent period; multiple causes; penetrance variable; unknown critical period; may not be reversible 2. Deficiency- anemia, wasting, stunting; short latent period; single/few causes; high penetrance 3. Insufficiency- may have characteristics of either excess or deficiency; osteoporosis 4. Unknown- interactions among nutrients and other factors

Complexities in studying nutrients and disease Relationship between food and health is affected by

Complexities in studying nutrients and disease Relationship between food and health is affected by acute or chronic illnesses; access to health care; lifestyle Therefore, nutritional data needs to be collected with purpose in mind and clear hypotheses to enable reliable estimate of the relationship of interest - clear and testable research questions - consideration of the effects of other factors - exposures and outcomes of interest are measured with sufficient precision

The need for practical methods to measure diet Methods need to be: Accurate Relatively

The need for practical methods to measure diet Methods need to be: Accurate Relatively inexpensive Have high compliance

Debate Are useful measurements of the diet of individual subjects within free-living populations possible

Debate Are useful measurements of the diet of individual subjects within free-living populations possible to collect? Are diets of persons living within one country too homogeneous to detect relationship with disease?

Development of nutritional epidemiology � Development and evaluation of methods for dietary assessment in

Development of nutritional epidemiology � Development and evaluation of methods for dietary assessment in epidemiological applications is growing � Many aspects of diet can be measured readily with sufficient accuracy to provide useful information � Finding that meaningful between person variations within populations do exist � Identification of ways to deal with errors/limitations 1. Identify the principle sources of error 2. Explore the impact of these errors on the results 3. Design studies which prevent or control these errors

Gains in the field � Defining patterns of food consumption vs. . individual foods

Gains in the field � Defining patterns of food consumption vs. . individual foods � Discovery that the ways foods are stored and prepared influence impact � Study of whole foods in addition to specific nutrients � Causal pathway of nutrients � Development of measurement instruments � Knowing the sources, characteristics and effects of errors in the measurement of dietary exposures � Use of biomarkers to identify unreliable dietary intake reporting Need for improvement: � Determining the relevance of biomarkers or proxies for dietary intake � Identification of susceptible subgroups

Study Designs: Correlation or Ecologic � The exposure variable is the population per capita

Study Designs: Correlation or Ecologic � The exposure variable is the population per capita consumption of specific dietary factors � Relies on disappearance data (food produced and imported minus food exported and fed to animals) � Some correlations strong (0. 85 for meat intake and colon cancer incidence) � Strengths: contrasts in dietary intake are typically large (fat intake between US and nonwestern nations); diets at a regional level are stable over time; values are derived from large populations and are subject to only small random errors

Study Designs: Correlation or Ecologic � Weaknesses: highly correlated with other factors (GNP); disappearance

Study Designs: Correlation or Ecologic � Weaknesses: highly correlated with other factors (GNP); disappearance data may lead to erroneous conclusions (alcohol consumption and breast cancer- who is drinking the alcohol in the population? ); cannot be independently reproduced � Solutions: collect information on actual dietary intake in a uniform manner from the population subgroups of interest; China has 65 geographical areas with unusually large variation in rates of many cancers; select men vs. women; etc.

Study Designs: Correlation or Ecologic Special Exposure Groups � Seventh-day Adventists (SDA): vegetarian, have

Study Designs: Correlation or Ecologic Special Exposure Groups � Seventh-day Adventists (SDA): vegetarian, have half the expected colon cancer rates of non-SDA in the same geographical region � Subject to same strengths/weaknesses as ecological studies, but useful in refuting hypothesis; i. e. , SDA abstain from alcohol consumption yet do not have significantly different rates of breast cancer mortality than non-SDA

Study Designs: Correlation or Ecologic Migrant Studies and Secular Trends � Migrant studies show

Study Designs: Correlation or Ecologic Migrant Studies and Secular Trends � Migrant studies show influence of environmental exposures in contrast to genetic factors � Secular trends likewise may reveal non-genetic factors that are influential

Study Designs: Case-Control � Control for confounding by design (matching, restriction) or in the

Study Designs: Case-Control � Control for confounding by design (matching, restriction) or in the analysis (multivariate methods) if confounding variables are known � However, for dietary studies, bias may seriously effect outcome � Due to the limited range of variation in diet, the relative risks are modest (0. 5 -2) and even a small error in measuring intake (3 -4%), which is difficult to avoid (recall bias), can distort relative relationship � Inconsistent findings between studies would be predicted and are indeed found in the literature

Study Designs: Case-Control � Selection of controls with medical conditions may potentially have diet

Study Designs: Case-Control � Selection of controls with medical conditions may potentially have diet related conditions � Inherent biological complexity � Nutrient-nutrient interactions may cause inconsistent results, but are nonetheless accurate � Even consistent findings may be wrong; i. e. , positive association between total energy intake and risk of colon cancer, that in prospective studies found either non or inverse associations

Study Designs: Cohort � Strength: less susceptible to bias � Weakness: may have low

Study Designs: Cohort � Strength: less susceptible to bias � Weakness: may have low frequency of outcome, more expensive, follow-ups Some populations are followed-up (standard of care for cancer patients) AND are inherently very interested in diet, so can find a committed population.

Study Designs: Controlled Trials � Undertaken only when there is a body of nonexperimental

Study Designs: Controlled Trials � Undertaken only when there is a body of nonexperimental data that justify benefit to humans � High probability of finding lack of effect due to diets exerting effects after long period of time; duration of trial must be long and compliance must be high � Health conscious people tend to enroll, those at higher risk may not be included in study � Imprecise measure of effect because if benefit is observed, ethical considerations require stopping the trial

Measures of Exposure Types of measures � Dietary habits � Food patterns, meals, foods,

Measures of Exposure Types of measures � Dietary habits � Food patterns, meals, foods, nutrients � Individuals, groups, populations � Anthropometry � Biological � Knowledge/attitudes about food Expression of measures Continuous � Total cumulative dose (e. g. lifetime) � Average dose (e. g. average per day) � Percent of standard Discrete � Eat a particular food item � Rank (quartiles) � Percent above/below standard

Measures of Outcome Types of measures � Dietary habits � Anthropometry � Biological �

Measures of Outcome Types of measures � Dietary habits � Anthropometry � Biological � Physiological � Disease/health status � � Morbidity Mortality Expression of measures � Continuous � Categorized into discrete (e. g. cut-points: BP, obese, syndromes)

Measures for the relationship between exposure and outcome � Average level of group outcome

Measures for the relationship between exposure and outcome � Average level of group outcome in discrete categories of exposure (e. g. BP levels by thirds of fat intake) � Regression (change in outcome per unit change in exposure) � Standardized morbidity or mortality ratios � Absolute risk or absolute risk reduction � Relative risk (ratio of the rates of appearance of outcomes in different categories of exposure) � Attributable risk percent (proportion of cases in the exposed population that can be attributed to the risk factor) � Number needed to treat (number of subjects in whom the exposure needs to be altered in order to save one person from getting the outcome)

Interpretation of null results � Variation in diet is insufficient � Variation may exist

Interpretation of null results � Variation in diet is insufficient � Variation may exist but only within the no effect range of the dose response curve � Method of measuring dietary intake is not sufficiently precise to measure differences that truly exist � Low statistical power � Temporal relationship between the measured exposure the occurrence of the disease did not encompass the true latency period � Unmeasured third variable was related to exposure and disease in opposite directions; negative confounding � Methodological sources of bias

Issues of nutritional epidemiology 1. 2. 3. 4. 5. Measurements of diet lack precision

Issues of nutritional epidemiology 1. 2. 3. 4. 5. Measurements of diet lack precision and specificity Nutrient intakes are highly correlated; attribution of causation to one nutrient considered to be acting on its own may be misleading Biological measurements of nutrients in tissues may not accurately or reliably reflect dietary intake; biological regulation of these measurements is complex, may be influenced by other nutrients, homeostasis Lack of consideration of the effects of the way food is prepared (whole, processed, extracts) Everyone is exposed to causal/preventive factors, i. e. everyone eats fats, fiber, vitamins over a lifetime

Issues in study design and interpretation of results � If null finding is observed,

Issues in study design and interpretation of results � If null finding is observed, you should define the conditions and limitations of the null finding � Demonstrate that true variation exists in the diet and that method of measuring diet is adequate for detecting variation � No study instrument is without some potential source of error; use valid instrument of study � Report confidence intervals

Issues in study design and interpretation of results (cont. ) � Range of latency

Issues in study design and interpretation of results (cont. ) � Range of latency period should be discussed. Case-control study of cancer describe over what time period dietary intake was reported; Prospective study may allow analysis over different times � Describe the dietary and non-dietary correlates of the primary exposure what has been evaluated as potential confounding variables

Types of Measurements �Twenty-four-hour Recall is an attempt to define and quantify food intake

Types of Measurements �Twenty-four-hour Recall is an attempt to define and quantify food intake during a specific day. �Dietary Records are detailed descriptions of types and amounts of foods and beverages consumed, meal by meal, over a prescribed period (3 -7 days). �Food Frequency Methods collect long-term diet over months or years, not just a few days.

Different levels of information concerning diet Food Item/Food group level red meat, fish, butter,

Different levels of information concerning diet Food Item/Food group level red meat, fish, butter, vegetable oil, cruciferous vegetables, coffee, beer salted, smoked, pickled, fried, cured foods Nutrient Level energy, animal protein, fat, vitamin c, selenium Other Factors nitrates/nitrites, food additives, contaminants, mutagens and carcinogens, antioxidants

Measurement Techniques of Food Consumption Food Recording Techniques �Weighing method: (1) precise weighing (weighing

Measurement Techniques of Food Consumption Food Recording Techniques �Weighing method: (1) precise weighing (weighing both before and after cooking); (2) weighed inventory (weighing only after cooking) �Recording in household measures Interview methods �Recall Methods (usually 24 H) �Dietary history and food frequency methods

Food Frequency Questionnaire based on Dietary History �Measures the habitual diet of the subject

Food Frequency Questionnaire based on Dietary History �Measures the habitual diet of the subject at least qualitatively and half-quantitatively �Frequency and portion size of use 100 -200 food items are asked as well as the usual eating pattern. �Refers to the previous month or year �Seasonal difference are asked � 60 -90 minutes interview �The best method of estimating the habitual diet of an individual over a long time period �Idea in diet and cancer studies

New Challenge for Nutritional Epidemiology: Cancer and Chronic Disease �Occur with a low frequency

New Challenge for Nutritional Epidemiology: Cancer and Chronic Disease �Occur with a low frequency with multiple causes acting alone or in combination (nutrition, smoking, drinking, occupational exposure, physical activity, etc. ) �Occur only among exposed but also among unexposed. (everyone eats fat, fiber, vitamins).

New Challenge for Nutritional Epidemiology: Cancer and Chronic Disease �Have a longer latent time

New Challenge for Nutritional Epidemiology: Cancer and Chronic Disease �Have a longer latent time (20 -40 years for cancer) or unknown. �Not readily reversible, may result from excessive or insufficient intake of dietary factors, which makes the intervention difficult

Percentage of Cancer Deaths Attributed to Various Factors (Doll R and Peto R, JNCI,

Percentage of Cancer Deaths Attributed to Various Factors (Doll R and Peto R, JNCI, 1981) �Tobacco Use: 30% (25%-40%) �Diet: 35% (10%-70%) �Infection: 10%? (1%-? ) �Reproductive & Sexual Behavior: 7% (1%-13%) �Occupation: 4% (<2%-8%) �Alcohol: 3% (2%-4%) �Geophysical factors (natural radiation): 3% (2 -4%) �Pollution: 2% (<1% – 5%) �Food additives: <1% (-5% – 2%) �Medicines/Medical Procedures: 1% (0. 5%-3%) �Industrial consumer products: <1% (<1%-2%) �Unknown: ?

Harvard Center for Cancer Prevention (www. hsph. harvard. edu/cancer) �Tobacco: 30% �Diet in adult

Harvard Center for Cancer Prevention (www. hsph. harvard. edu/cancer) �Tobacco: 30% �Diet in adult life, including obesity: 30% �Sedentary lifestyle: 5% �Infectious agents: 5% �Defects in single genes that run in family: 5 -10%