Lawrence H. Kushi

Adjustment for total energy intake in epidemiologic studies.

In epidemiologic studies, total energy intake is often related to disease risk because of associations between physical activity or body size and the probability of disease. In theory, differences in disease incidence may also be related to metabolic efficiency and therefore to total energy intake. Because intakes of most specific nutrients, particularly macronutrients, are correlated with total energy intake, they may be noncausally associated with disease as a result of confounding by total energy intake. In addition, extraneous variation in nutrient intake resulting from variation in total energy intake that is unrelated to disease risk may weaken associations. Furthermore, individuals or populations must alter their intake of specific nutrients primarily by altering the composition of their diets rather than by changing their total energy intake, unless physical activity or body weight are changed substantially. Thus, adjustment for total energy intake is usually appropriate in epidemiologic studies to control for confounding, reduce extraneous variation, and predict the effect of dietary interventions. Failure to account for total energy intake can obscure associations between nutrient intakes and disease risk or even reverse the direction of association. Several disease-risk models and formulations of these models are available to account for energy intake in epidemiologic analyses, including adjustment of nutrient intakes for total energy intake by regression analysis and addition of total energy to a model with the nutrient density (nutrient divided by energy).

DIETARY ANTIOXIDANT VITAMINS AND DEATH FROM CORONARY HEART DISEASE IN POSTMENOPAUSAL WOMEN

Background. The role of dietary antioxidant vitamins in preventing coronary heart disease has aroused considerable interest because of the knowledge that ox- idative modification of low-density lipoprotein may pro- mote atherosclerosis. Methods. We studied 34,486 postmenopausal wom- en with no cardiovascular disease who in early 1986 com- pleted a questionnaire that assessed, among other fac- tors, their intake of vitamins A, E, and C from food sources and supplements. During approximately seven years of follow-up (ending December 31, 1992), 242 of the women died of coronary heart disease. Results. In analyses adjusted for age and dietary en- ergy intake, vitamin E consumption appeared to be in- versely associated with the risk of death from coronary heart disease. This association was particularly striking in the subgroup of 21,809 women who did not consume vitamin supplements (relative risks from lowest to highest quintile of vitamin E intake, 1.0, 0.68, 0.71, 0.42, and 0.42; P for trend � 0.008). After adjustment for possible con- founding variables, this inverse association remained (rel- ative risks from lowest to highest quintile, 1.0, 0.70, 0.76, 0.32, and 0.38; P for trend � 0.004). There was little evi- dence that the intake of vitamin E from supplements was associated with a decreased risk of death from coronary heart disease, but the effects of high-dose supplementa- tion and the duration of supplement use could not be de- finitively addressed. Intake of vitamins A and C did not appear to be associated with the risk of death from cor- onary heart disease. Conclusions. These results suggest that in postmeno- pausal women the intake of vitamin E from food is inverse- ly associated with the risk of death from coronary heart disease and that such women can lower their risk without using vitamin supplements. By contrast, the intake of vita- mins A and C was not associated with lower risks of dying from coronary disease. (N Engl J Med 1996;334:1156-62.)

American Cancer Society guidelines on nutrition and physical activity for cancer prevention

The American Cancer Society (ACS) publishes Nutrition and Physical Activity Guidelines to serve as a foundation for its communication, policy, and community strategies and, ultimately, to affect dietary and physical activity patterns among Americans. These Guidelines, published approximately every 5 years, are developed by a national panel of experts in cancer research, prevention, epidemiology, public health, and policy, and they reflect the most current scientific evidence related to dietary and activity patterns and cancer risk. The ACS Guidelines focus on recommendations for individual choices regarding diet and physical activity patterns, but those choices occur within a community context that either facilitates or creates barriers to healthy behaviors. Therefore, this committee presents recommendations for community action to accompany the 4 recommendations for individual choices to reduce cancer risk. These recommendations for community action recognize that a supportive social and physical environment is indispensable if individuals at all levels of society are to have genuine opportunities to choose healthy behaviors. The ACS Guidelines are consistent with guidelines from the American Heart Association and the American Diabetes Association for the prevention of coronary heart disease and diabetes, as well as for general health promotion, as defined by the 2010 Dietary Guidelines for Americans and the 2008 Physical Activity Guidelines for Americans. CA Cancer J Clin 2012.

Cohort Studies of Fat Intake and the Risk of Breast Cancer — A Pooled Analysis

BACKGROUND Experiments in animals, international correlation comparisons, and case-control studies support an association between dietary fat intake and the incidence of breast cancer. Most cohort studies do not corroborate the association, but they have been criticized for involving small numbers of cases, homogeneous fat intake, and measurement errors in estimates of fat intake. METHODS We identified seven prospective studies in four countries that met specific criteria and analyzed the primary data in a standardized manner. Pooled estimates of the relation of fat intake to the risk of breast cancer were calculated, and data from study-specific validation studies were used to adjust the results for measurement error. RESULTS Information about 4980 cases from studies including 337,819 women was available. When women in the highest quintile of energy-adjusted total fat intake were compared with women in the lowest quintile, the multivariate pooled relative risk of breast cancer was 1.05 (95 percent confidence interval, 0.94 to 1.16). Relative risks for saturated, monounsaturated, and polyunsaturated fat and for cholesterol, considered individually, were also close to unity. There was little overall association between the percentage of energy intake from fat and the risk of breast cancer, even among women whose energy intake from fat was less than 20 percent. Correcting for error in the measurement of nutrient intake did not materially alter these findings. CONCLUSIONS We found no evidence of a positive association between total dietary fat intake and the risk of breast cancer. There was no reduction in risk even among women whose energy intake from fat was less than 20 percent of total energy intake. In the context of the Western lifestyle, lowering the total intake of fat in midlife is unlikely to reduce the risk of breast cancer substantially.

Nutrition and Physical Activity During and After Cancer Treatment: An American Cancer Society Guide for Informed Choices†

Cancer survivors are often highly motivated to seek information about food choices, physical activity, and dietary supplement use to improve their treatment outcomes, quality of life, and survival. To address these concerns, the American Cancer Society (ACS) convened a group of experts in nutrition, physical activity, and cancer to evaluate the scientific evidence and best clinical practices related to optimal nutrition and physical activity after the diagnosis of cancer. This report summarizes their findings and is intended to present health care providers with the best possible information from which to help cancer survivors and their families make informed choices related to nutrition and physical activity. The report discusses nutrition and physical activity issues during the phases of cancer treatment and recovery, living after recovery from treatment, and living with advanced cancer; select nutrition and physical activity issues such as body weight, food choices, and food safety; issues related to select cancer sites; and common questions about diet, physical activity, and cancer survivorship.

Diet and 20-year mortality from coronary heart disease: the Ireland-Boston Diet-Heart Study.

In a prospective epidemiologic study of 1001 middle-aged men, we examined the relation between dietary information collected approximately 20 years ago and subsequent mortality from coronary heart disease. The men were initially enrolled in three cohorts: one of men born and living in Ireland, another of those born in Ireland who had emigrated to Boston, and the third of those born in the Boston area of Irish immigrants. There were no differences in mortality from coronary heart disease among the three cohorts. In within-population analyses, those who died of coronary heart disease had higher Keys (P = 0.06) and modified Hegsted (P = 0.02) dietary scores than did those who did not (a high score indicates a high intake of saturated fatty acids and cholesterol and a relatively low intake of polyunsaturated fatty acids). These associations were significant (P = 0.03 for the Keys and P = 0.04 for the modified Hegsted scores) after adjustment for other risk factors for coronary heart disease. Fiber intake (P = 0.04) and a vegetable-foods score, which rose with increased intake of fiber, vegetable protein, and starch (P = 0.02), were lower among those who died from coronary heart disease, though not significantly so after adjustment for other risk factors. A higher Keys score carried an increased risk of coronary heart disease (relative risk, 1.60), and a higher fiber intake carried a decreased risk (relative risk, 0.57). Overall, these results tend to support the hypothesis that diet is related, albeit weakly, to the development of coronary heart disease.

Sugar, meat, and fat intake, and non-dietary risk factors for colon cancer incidence in Iowa women (United States)

To investigate the relation of dietary intakes of sucrose, meat, and fat, and anthropometric, lifestyle, hormonal, and reproductive factors to colon cancer incidence, data were analyzed from a prospective cohort study of 35,215 Iowa (United States) women, aged 55–69 years and without a history of cancer, who completed mailed dietary and other questionnaires in 1986. Through 1990, 212 incident cases of colon cancer were documented. Proportional hazards regression was used to adjust for age and other risk factors. Risk factors found to be associated significantly with colon cancer included: (i) sucrose-containing foods and beverages other than ice cream/milk; relative risks (RR) across the quintiles=1.00, 1.73, 1.56, 1.54, and 2.00 (95% confidence intervals [CI] for quintiles two and five exclude 1.0); (ii) sucrose; RR across the quintiles=1.00, 1.70, 1.81, 1.82, and 1.45 (CI for quintiles two through four exclude 1.0); (iii) height; RR=1.23 for highest to lowest quintile (P for trend-0.02); (iv) body mass index; RR=1.41 for highest to lowest quintile (P for trend=0.03); and (v) number of livebirths, RR=1.59 for having had one to two livebirths and 1.80 for having had three or more livebirths compared with having had none (P for trend=0.04). These data support hypotheses that sucrose intake or being tall or obese increases colon cancer risk; run contrary to the hypothesis that increased parity decreases risk; support previous findings of no association with demographic factors other than age, cigarette smoking, or use of oral contraceptives or estrogen replacement therapy; and raise questions regarding previous associations with meat, fat, protein, and physical activity.Cancer Causes and Control 1994, 5, 38–52.

Early Discontinuation and Nonadherence to Adjuvant Hormonal Therapy in a Cohort of 8,769 Early-Stage Breast Cancer Patients

PURPOSE While studies have found that adjuvant hormonal therapy for hormone-sensitive breast cancer (BC) dramatically reduces recurrence and mortality, adherence to medications is suboptimal. We investigated the rates and predictors of early discontinuation and nonadherence to hormonal therapy in patients enrolled in Kaiser Permanente of Northern California health system. PATIENTS AND METHODS We identified women diagnosed with hormone-sensitive stage I-III BC from 1996 to 2007 and used automated pharmacy records to identify hormonal therapy prescriptions and dates of refill. We used Cox proportional hazards regression models to analyze factors associated with early discontinuation and nonadherence (medication possession ratio < 80%) of hormonal therapy. RESULTS We identified 8,769 patients with BC who met our eligibility criteria and who filled at least one prescription for tamoxifen (43%), aromatase inhibitors (26%), or both (30%) within 1 year of diagnosis. Younger or older age, lumpectomy (v mastectomy), and comorbidities were associated with earlier discontinuation, while Asian race, being married, earlier year at diagnosis, receipt of chemotherapy or radiotherapy, and longer prescription refill interval were associated with completion of 4.5 years of therapy. Of those who continued therapy, similar factors were associated with full adherence. Women age younger than 40 years had the highest risk of discontinuation (hazard ratio, 1.51; 95% CI, 1.23 to 1.85). By 4.5 years, 32% discontinued therapy, and of those who continued, 72% were fully adherent. CONCLUSION Only 49% of patients with BC took adjuvant hormonal therapy for the full duration at the optimal schedule. Younger women are at high risk of nonadherence. Interventions to improve adherence and continuation of hormonal therapy are needed, especially for younger women.

Whole‐grain intake and cancer: An expanded review and meta‐analysis

Whole grains are nutrient rich and may protect against chronic disease. To study this, we previously reviewed 14 case-control studies of colorectal, gastric, and endometrial cancers and found consistently lower risk in those with high than in those with low whole-grain intake. Questions remained concerning other cancers, dietary assessment, quantity consumed, confounding, and differential study quality. Here we expand the review to 40 case-control studies of 20 cancers and colon polyps. Odds ratios are < 1 for 46 of 51 mentions of whole-grain intake and for 43 of 45 after exclusion of 6 mentions with design/reporting flaws or low intake. The pooled odds ratio for high vs. low whole-grain intake among the 45 mentions was 0.66 (95% confidence interval = 0.60-0.72); they range from 0.59 to 0.78 across four types of dietary questionnaires. Odds ratios were < 1 in 9 of 10 mentions of studies of colorectal cancers and polyps, 7 of 7 mentions of gastric and 6 of 6 mentions of other digestive tract cancers, 7 of 7 mentions of hormone-related cancers, 4 of 4 mentions of pancreatic cancer, and 10 of 11 mentions of 8 other cancers. Most pooled odds ratios for specific cancers were in the range of 0.5-0.8, notable exceptions being breast (0.86) and prostate (0.90). The pooled odds ratio was similar in studies that adjusted for few and many covariates. Dose-response associations were stronger in studies using food-frequency questionnaires than in more quantitative questionnaires. The case-control evidence is supportive of the hypothesis that whole-grain intake protects against various cancers.

Validity and reproducibility of the food frequency questionnaire used in the Shanghai Women's Health Study.

To evaluate the validity and reliability of the food frequency questionnaire (FFQ) used in the Shanghai Womens Health Study (SWHS), 200 SWHS participants were recruited for a dietary calibration study. Study participants completed an FFQ at baseline and 24-h dietary recalls (24-HDR) twice per month consecutively for 12 months. At the end of the study, a second FFQ was administered. Of the 200 study participants, 196 completed 24 or more days of 24-h dietary recalls, 191 completed two FFQs from whom the results of this report were based. The FFQ included the foods that accounted for 86% of the foods recorded in the 24-HDR surveys. Validity of the FFQ was evaluated by comparing intake levels of major nutrients and foods obtained from the second FFQ with those derived from the multiple 24-HDR. The median intake for major nutrients, rice, poultry and meat derived from the second FFQ and the 24-HDR was similar, with the differences ranging from 1.3 to 12.1%. The FFQ tended to overestimate the intake level of total vegetables and total fruits, and the differences were explained mainly by over-reporting seasonal vegetables and fruits consumption in the FFQ. Nutrient and food intake assessed by the FFQ and the multiple 24-HDR correlated very well, with the correlation coefficients being 0.59–0.66 for macronutrients, 0.41–0.59 for micronutrients, and 0.41–0.66 for major food groups. The reliability of the FFQ was assessed by comparing the correlation and median intake of nutrients and food groups obtained from the two FFQs that were administered approximately 2 y apart. The median intake levels for selected nutrients and food groups derived from the two FFQs were similar with differences below 10%. At the individual level, the intake levels of these dietary variables obtained from two FFQs also correlated well. When nutrient and food group intakes were categorized into quartiles, FFQ and 24-HDR produced exact agreement rates between 33 and 50%. Misclassification to adjacent quartile was common, ranging from 34–48%, while misclassification to an extreme quartile was rare (1–6%). These data indicate that the SWHS FFQ can reliably and accurately measure usual intake of major nutrients and food groups among women in Shanghai.