Contributions of diet to metabolic problems in survivors of childhood cancer

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Contributions of diet to metabolic problems in survivors of childhood cancer Kim Robien, PhD, RD, CSO, FAND Department of Exercise and Nutrition Sciences Milken Institute School of Public Health George Washington University krobien@gwu.edu

Chronic health conditions in adult survivors of childhood cancer 62.3% of cancer survivors reported at least one chronic condition. Survivors were 3.3 times as likely to have a chronic health condition compared to sibling controls (95% CI: 3.0-3.5) Relative Risk (95% CI) major joint replacement 54.0 (7.6-386.3) congestive heart failure 15.1 (4.8 47.9) second malignancy 14.8 (7.2 30.4) coronary artery disease 10.4 (4.1 25.9) cerebrovascular accident 9.3 (4.1 21.2) Oeffinger et al, 2006 PMID: 17035650

Metabolic syndrome Characteristics: Abdominal obesity Dyslipidemia Raised blood pressure Insulin resistance ± glucose intolerance Prothrombotic state Proinflammatory state Predictive of increased risk of cardiovascular disease and type 2 diabetes Preventable with appropriate diet and physical activity

National Cholesterol Education Program ATPIII: Clinical Identification of the Metabolic Syndrome (2001) Metabolic syndrome is identified by the presence of 3 or more risk factors listed in this table.

Prevalence of metabolic syndrome among adult survivors of childhood cancer Author/ date N Age at interview Cancer diagnoses included Prevalence of metabolic syndrome MetSyn criteria used Gurney, 2006 75 Mean: 30 years Acute lymphoblastic leukemia 17% * ATP III Van Waas, 2010 500 Median: 28 Range: 18-59 All childhood cancers 13% ** modified definition of MetSyn, Haugnes et al Smith, 2014 1598 Range: 19-60 All childhood cancers 32% * ATP III * Not statistically significantly different from general population (NHANES) ** No comparison group Prevalence of metabolic syndrome in the US adult population: 34% (NHANES 2003-2006)

Factors associated with metabolic syndrome in adult survivors of childhood cancer Advanced age Lower educational attainment Treatment regimens containing cranial radiotherapy (CRT) Failure to follow dietary recommendations Sedentary lifestyle

Dietary pattern scores Scores that describe adherence to recommendations on dietary factors for disease prevention Accounts for the complexity of diet, collinearity between dietary components Can be either translated into dietary recommendations, or used to test the effectiveness of existing recommendations Examples: Mediterranean Diet Score Healthy Eating Index Alternate Healthy Eating Index DASH Score WCRF/AICR Adherence score

World Cancer Research Fund / American Institute for Cancer Research (2007) Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective Recommendation for Cancer Survivors: Follow the recommendations for cancer prevention Recommendations for cancer prevention: Maintain body weight within the normal range. Be moderately physically active. Get the equivalent of 30 minutes of brisk walking every day. As fitness improves, aim for 60 minutes or more of moderate exercise (or 30 minutes vigorous exercise) each day. (continues)

World Cancer Research Fund / American Institute for Cancer Research (2007) Food, Nutrition, Physical Activity and the Prevention of Cancer: A Global Perspective Recommendations for cancer prevention (continued): Consume calorie-dense foods sparingly. Avoid sugary drinks. Consume fast foods sparingly, if at all. Eat at least 5 servings of a variety of non-starchy vegetables and fruits each day. People who consume red meat should consume less than 18 oz per week, and very little (if any) should be processed. If alcohol is consumed, limit consumption to no more than two drinks a day for men, and one drink per day for women. Avoid salt-preserved, salted or salty foods. Dietary supplements are not recommended for cancer prevention.

Smith et al 2014, PMID: 25070001

Adherence to WCRF/AICR dietary recommendations by adult survivors of childhood cancer Author/ date N Mean age at interview Cancer diagnoses Findings Robien, 2008 72 29.9 years Acute lymphoblastic leukemia Mean adherence score: 2.9 (± 1.2) (out of 7) Smith, 2014 1598 32.7 years All childhood cancers 25.2% of males, 28.8% of females met at least 4 of the 7 recommendations

Dietary Approaches to Stop Hypertension (DASH) Diet Recommendations Total fat: 27% of calories Saturated fat: 6% of calories Protein: 18% of calories Carbohydrate: 55% of calories Cholesterol: 150 mg Sodium: 2,300 mg* Potassium: 4,700 mg Calcium: 1,250 mg Magnesium: 500 mg Fiber: 30 g * 1,500 mg sodium was a lower goal tested and found to be even better for lowering blood pressure. It was particularly effective for middle-aged and older individuals, African Americans, and those who already had high blood pressure. g = grams; mg = milligrams

Adherence to the DASH Diet by adult survivors of childhood cancer 72 adult survivors of ALL Mean age at interview: 29.9 ± 7.3 years Robien et al, 2008. PMID: 18989158 Mean DASH diet score: 3.6 (±1.5) Mean sodium intake: 3113 mg/day Half the participants consumed the recommended 5 servings of fruits, vegetables - significantly better than the general population according to Behavioral Risk Factor Surveillance Survey (BRFSS)

WCRF/AICR adherence and metabolic syndrome among adult survivors of childhood cancer Smith et al, 2014 (PMID: 25070001), St Jude Lifetime Cohort 1598 adult survivors of childhood cancers Participants who did not follow at least 4 of the 7 WCRF/AICR recommendations were at increased risk for metabolic syndrome Females RR 2.4 (95% CI: 1.7-3.3) Males RR 2.2 (95% CI: 1.6-3.0) adjusted for age, race, CRT, education, smoking status, age at diagnosis

Mediterranean Diet and metabolic syndrome among adult survivors of childhood cancer Tonorezos et al, 2012 (PMID: 23187859), ALLIFE Study 117 adult survivors of childhood acute lymphoblastic leukemia Mediterranean Diet characterized by high intake of fruits, vegetables, fish and legumes; low intake of meat and dairy products Mean Mediterranean Diet Score (total possible score: 8): Females: 4.5 (± 1.6) Males: 3.9 (± 1.8) For each one point increase in adherence to a Mediterranean dietary pattern, odds of developing metabolic syndrome fell by 31% (OR 0.69, 95% CI: 0.50-0.94) Better adherence to the Mediterranean diet pattern was associated with lower visceral and subcutaneous adiposity, even after adjustment for age, gender, physical activity and total caloric intake

Additional diet related findings Small (n=26) study of adult survivors of childhood ALL had a mean MEDFICTS score that indicated non-compliance with the National Cholesterol Education Plan (NCEP) recommendations for total and saturated fat (PMID: 11878576) Among survivors of childhood ALL (n=164), less than 30% met recommended dietary intakes for vitamin D, calcium, potassium, or magnesium (PMID: 20981691) Children/adolescent cancer survivors tend to consume more healthful diets that adult survivors (PMID: 15812823, 7623724)

Limitations of the research to date Many studies have been small, single institution analyses Mostly cross-sectional, observational studies Very few studies have used comprehensive dietary assessment methods. Few studies have included a control group, or compared their findings to age-appropriate population data Lack of intervention studies to determine whether dietary intervention decreases risk of metabolic syndrome and other chronic diseases

Take-home messages As is true for the general US population, on average, survivors of childhood cancers are not compliant with dietary recommendations to prevent chronic diseases. Compliance with WCRF/AICR diet and physical activity recommendations appears to decrease the risk of metabolic syndrome, and may prevent progression to chronic disease in this high-risk segment of the population Intervention studies are needed to evaluate the effectiveness of diet and physical activity interventions among adult survivors of childhood cancers