Christine A. Swanson

Nutrition and lung cancer

Epidemiologic evidence on the relationship between nutrition and lung cancer is reviewed. Observational studies of diet and lung cancer, both prospective and retrospective, continue to suggest strongly that increased vegetable and fruit intake is associated with reduced risk in men and women; in various countries; in smokers, ex-smokers, and never-smokers; and for all histologic types of lung cancer. Prospective studies of blood β-carotene levels, arguably the best available biomarker of vegetable and fruit intake, indicate that low levels are predictive of increased lung cancer incidence. However, in a randomized, placebo-controlled clinical trial in male smokers, lung cancer incidence and total mortality were increased significantly among the men receiving β-carotene supplements. If β-carotene can prevent lung carcinogenesis, which the trial cannot rule out, then the dosage, duration of use, method of administration, and/or subpopulation are critical. Ongoing clinical trials, some of which include women, will provide much-needed information. Other carotenoids, other phytochemicals, and associated dietary patterns may explain the beneficial effects of vegetables and fruits and have not been explored adequately in epidemiologic work. Several observational epidemiologic studies, both prospective and retrospective, have indicated that diets high in fat, saturated fat, and cholesterol may increase the risk of lung cancer and that the effect is not mediated through vegetable and fruit intake. The relationship, although not yet established, merits further investigation. Since β-carotene can function as an antioxidant, other micronutrients with this potential, specifically vitamins E and C and selenium, also have been proposed to reduce lung cancer risk. However, the totality of the epidemiologic evidence is not, at present, persuasive for any one of these micronutrients.

Relationships of serum carotenoids, retinol, alpha-tocopherol, and selenium with breast cancer risk: results from a prospective study in Columbia, Missouri (United States)

To evaluate relationships of serum carotenoids, α-tocopherol, selenium, and retinol with breast cancer prospectively, we conducted a case-control study nested in a cohort from the Breast Cancer Serum Bank in Columbia, Missouri (United States). Women free of cancer donated blood to this bank in 1977-87. During up to 9.5 years of follow-up (median = 2.7 years), 105 cases of histologically confirmed breast cancer were diagnosed. For each case, two women alive and free of cancer at the age of the cases diagnosis and matched on age and date of blood collection were selected as controls. A nonsignificant gradient of decreasing risk of breast cancer with increasing serum β-cryptoxanthin was apparent for all women. Serum lycopene also was associated inversely with risk, and among women who donated blood at least two years before diagnosis, a significant gradient of decreasing breast cancer risk with increasing lycopene concentration was evident. Amarginally significant gradient of decreasing risk with increasing serum lutein/zeaxanthin also was apparent among these women. We did not observe any evidence for protective effects of α- and β-carotene, α-tocopherol, retinol, or selenium for breast cancer. Results of this study suggest that the carotenoids β-cryptoxanthin, lycopene, and lutein/zeaxanthin may protect against breast cancer.

Alcohol, intestinal bacterial growth, intestinal permeability to endotoxin, and medical consequences: summary of a symposium.

This report is a summary of the symposium on Alcohol, Intestinal Bacterial Growth, Intestinal Permeability to Endotoxin, and Medical Consequences, organized by National Institute on Alcohol Abuse and Alcoholism, Office of Dietary Supplements, and National Institute of Diabetes and Digestive and Kidney Diseases of National Institutes of Health in Rockville, Maryland, October 11, 2006. Alcohol exposure can promote the growth of Gram-negative bacteria in the intestine, which may result in accumulation of endotoxin. In addition, alcohol metabolism by Gram-negative bacteria and intestinal epithelial cells can result in accumulation of acetaldehyde, which in turn can increase intestinal permeability to endotoxin by increasing tyrosine phosphorylation of tight junction and adherens junction proteins. Alcohol-induced generation of nitric oxide may also contribute to increased permeability to endotoxin by reacting with tubulin, which may cause damage to microtubule cytoskeleton and subsequent disruption of intestinal barrier function. Increased intestinal permeability can lead to increased transfer of endotoxin from the intestine to the liver and general circulation where endotoxin may trigger inflammatory changes in the liver and other organs. Alcohol may also increase intestinal permeability to peptidoglycan, which can initiate inflammatory response in liver and other organs. In addition, acute alcohol exposure may potentiate the effect of burn injury on intestinal bacterial growth and permeability. Decreasing the number of Gram-negative bacteria in the intestine can result in decreased production of endotoxin as well as acetaldehyde which is expected to decrease intestinal permeability to endotoxin. In addition, intestinal permeability may be preserved by administering epidermal growth factor, l-glutamine, oats supplementation, or zinc, thereby preventing the transfer of endotoxin to the general circulation. Thus reducing the number of intestinal Gram-negative bacteria and preserving intestinal permeability to endotoxin may attenuate alcoholic liver and other organ injuries.

Design and methods of a population-based natural history study of cervical neoplasia in a rural province of Costa Rica: the Guanacaste Project

This paper reports on the enrollment phase of a population-based natural history study of cervical neoplasia in Guanacaste, a rural province of Costa Rica with consistently high rates of invasive cervical cancer. The main goals of the study are to investigate the role of human papillomavirus (HPV) infection and its co-factors in the etiology of high-grade cervical neoplasia, and to evaluate new cervical cancer screening technologies. To begin, a random sample of censal segments was selected and enumeration of all resident women 18 years of age and over was conducted with the aid of outreach workers of the Costa Rican Ministry of Health. Of the 10738 women who were eligible to participate, 10049 (93.6%) were interviewed after giving written informed consent. After the interview on cervical cancer risk factors was administered, a pelvic examination was performed on those women who reported previous sexual activity. The pelvic examination included a vaginal pH determination and collection of cervical cells for cytologic diagnosis using three different techniques. Additional cervical cells were collected for determination of the presence and amount of DNA from 16 different types of HPV, and two photographic images of the cervix were taken and interpreted offsite by an expert colposcopist. Finally, blood samples were collected for immunologic and micronutrient assays. Women with any abnormal cytologic diagnosis or a positive Cervigram, as well as a sample of the whole group, were referred for colposcopy, and biopsies were taken when lesions were observed. The enrollment screening will serve as the basis for a prevalent case-control study, and the members of the cohort free from serious disease will be followed actively, at intervals of no more than a year, to study the natural history of HPV infection and the origins of high-grade squamous intraepithelial lesions (HSIL). Details of the field operation are outlined, with particular reference to the realization of this kind of study in developing countries. Descriptive data on the prevalence of disease and exposure to various risk factors are also presented.

Use of selenium concentration in whole blood, serum, toenails, or urine as a surrogate measure of selenium intake.

&NA; We examined the validity of using the selenium level in a single biological specimen as a surrogate measure of usual intake. We used data from 77 free‐living adults from South Dakota and Wyoming. Subjects provided multiple 1‐day duplicate‐plate food composites, repeated specimens of blood and toenails, and 24‐hour urine collections. We developed a statistical calibration method that incorporated measurement error correction to analyze the data. The Pearson correlation coefficients between selenium intake and a single selenium status measure, after deattenuation to adjust for the effect of within‐person variation in intake, were: 0.78 for whole blood, 0.74 for serum, 0.67 for toenails, and 0.86 for urine. We present formulas to estimate the intake of individuals, based on selenium levels in a single specimen of blood, toenails, or urine. In these data, the concentration of selenium in a single specimen of whole blood, serum, or toenails served reasonably well as a measure for ranking subjects according to long‐term selenium intake but provided only a rough estimate of intake for each subject.

Height and weight at various ages and risk of breast cancer

A study of 1529 breast cancer patients and 1901 control subjects enabled evaluation of risk in relation to lifetime changes in body size. Tallness, regardless of when achieved, was associated with an increased risk of breast cancer diagnosed at both young (< 50 years) and older ages, with adult height of 68 in or more increasing risk by nearly 50 to 80% compared with statures of less than 62 in. The association of risk with weight was less clear. Subjects who described themselves as heavier than average at ages 8 to 9 or 16 years were at reduced risk, particularly for older-onset breast cancer. Higher body mass indices based on reported weights during early adulthood were also associated with reduced risk. Measures of body mass beyond the age of 20, however, were less strongly related to risk. These inconsistent patterns appeared to be explained by an effect on risk of weight gain later in life, which was related to reduced risks for young-onset breast cancer and increased risks for later disease. The effect of weight change for early-onset breast cancer was not restricted to in situ cancers and could therefore not be attributed to detection bias. The direct relationship of body mass change with older onset disease was restricted to invasive cancers, consistent with observations of poor breast cancer prognosis among obese women. Further attention on the relationship of anthropometric variables to risk of breast cancer should focus on the timing of weight gain as well as the distribution of body fat.

Intake of food groups and associated micronutrients in relation to risk of early-stage breast cancer†

Epidemiologic studies have evaluated the risk of breast cancer related to dietary fat intake, but only recently have other dietary factors received attention. Frequent intakes of fruit, vegetables and fiber have been associated with low risk of the disease in some studies but results are inconsistent. In a large case‐control study of early‐onset breast cancer, we evaluated risk related to a variety of food groups, associated micronutrients and non‐nutritive constituents. Cases treated with chemotherapy appeared to have altered reporting of food intake and were excluded. Analyses were restricted to 568 cases with in situ and localized disease and 1,451 population‐based controls. Reduced risks were observed for high intake of cereals and grains [odds ratio (OR) = 0.84, 95% confidence interval (CI) = 0.6–1.1 for highest compared with lowest quartile], vegetables (OR = 0.86, 95% CI = 0.6–1.1), beans (OR = 0.87, 95% CI = 0.7–1.2) and fiber from beans (OR = 0.88, 95% CI = 0.7–1.2). However, no trends of decreasing risk across quartiles of increasing intake were observed. Risk was not associated with dietary constituents related to these food groups including dietary fiber, carotenoids, vitamins A, C and E and folate. Incorporation of information from vitamin supplements did not alter the results for micronutrients. Our data suggest that intakes of cereals and grains, vegetables and beans are associated with minimal, if any, reduction in risk of early‐stage breast cancer among young women. Int. J. Cancer 82:315–321, 1999. Published 1999 Wiley‐Liss, Inc.

Body weight: estimation of risk for breast and endometrial cancers.

Consistent, positive, and independent associations between body weight or body mass index (BMI), weight gain, and various measures of central adiposity and the incidence of endometrial cancer exist. Increases in relative risks of 2-3.5 are reported for women with BMIs (in kg/m2) > or = 28-30, for women in the fourth compared with the first quartile of measures of central adiposity, and for women with weight gains from young adulthood to middle age of > or = 27 kg. Furthermore, endometrial cancer mortality is increased in heavier and taller women. Associations between breast cancer incidence and these measures of adiposity vary by age and menopausal status at the time of diagnosis. Heavier women appear to be at decreased risk for developing premenopausal breast cancer; relative risks of approximately 0.6 were reported for women with BMIs > or = 26-27. Conversely, heavier women are at increased risk of developing and dying from postmenopausal breast cancer. Although contradictory findings have been observed in cohort studies, modest increases in relative risks on the order of 1.2-1.5 were reported in older postmenopausal women with BMIs of > or = 28-30. Furthermore, adult weight gain and increased central adiposity have been consistently and independently associated with an increased risk for postmenopausal breast cancer. No significant associations have been observed between weight loss and postmenopausal breast cancer incidence. These findings indicate that avoidance of weight gain and accumulation of central body fat during adult life may reduce risk of both endometrial and postmenopausal breast cancer.

General and Abdominal Obesity and Survival among Young Women with Breast Cancer

Among postmenopausal women, obesity is linked to increased risk of breast cancer and poorer subsequent survival. For premenopausal women, obesity may reduce incidence, but less is known about its effect on prognosis, particularly for abdominal obesity. This study investigated whether general or abdominal obesity at diagnosis influenced survival in a cohort of young women with breast cancer. A population-based follow-up study was conducted among 1,254 women ages 20 to 54 who were diagnosed with invasive breast cancer between 1990 and 1992 in Atlanta or New Jersey. Women were interviewed within several months of diagnosis and asked about their weight and height at age 20 and in the year before diagnosis. Study personnel did anthropometric measures at the interview. With 8 to 10 years of follow-up, all-cause mortality status was determined using the National Death Index (n = 290 deaths). Increased mortality was observed for women who were obese [body mass index (BMI), ≥30] at the time of interview compared with women of ideal weight [BMI, 18.5-24.9; stage- and income-adjusted hazard ratio (HR), 1.48; 95% confidence interval (95% CI), 1.09-2.01]. A similar result was seen for the highest versus lowest quartile of waist-to-hip ratio (HR, 1.52; 95% CI, 1.05-2.19). Strong associations with mortality were found for women who were obese at age 20 (HR, 2.49; 95% CI, 1.15-5.37) or who were overweight/obese (BMI, ≥25) at both age 20 and the time of interview (HR, 2.22; 95% CI, 1.45-3.40). This study provides evidence that breast cancer survival is reduced among younger women with general or abdominal obesity. (Cancer Epidemiol Biomarkers Prev 2006;15(10):1871–7)

FRIED, WELL-DONE RED MEAT AND RISK OF LUNG CANCER IN WOMEN (UNITED STATES)

Objective: Some epidemiological studies suggest that diets high in fat, saturated fat, or cholesterol are associated with increased risk of lung cancer. Since meat consumption is correlated with the intake of saturated fat and cholesterol, we investigated the role of meat intake and cooking practices in relation to lung cancer risk.Methods: A population-based case-control study of both non-smoking and smoking women was conducted in Missouri. A 100-item food frequency questionnaire (FFQ) with detailed questions on meat consumption was completed by 593 cases and 623 frequency matched controls. We estimated quantity of meat eaten (grams/day) according to cooking method, and doneness level. Odds ratios (ORs) and 95% confidence intervals (C.I.s) were calculated using logistic regression. Multivariate models included age, packyears of smoking, body mass index (BMI, kg/m2), education, and intake of calories, fat, fruit/fruit juices, and vegetables.Results: When comparing 90th and 10th percentiles, lung cancer risk increased for total meat consumption (OR=1.6, C.I. 1.1-2.4), red meat (OR=1.8, C.I., 1.2-2.7), well-done red meat (OR=1.5, C.I.s, 1.1-2.1) and fried red meat (OR=1.5, C.I., 1.1-2.0). The odds ratios for 5th vs. 1st quintiles using the categorical variable for well-done red meat and fried red meat were essentially the same as reported above; however, the increase in risk was associated mainly with the 5th quintile. The ORs for a 10-gram increase in consumption were, 1.04 for total meat, 1.06 for red meat, 1.08 for well done red meat, and 1.09 for fried red meat.Conclusions: Consumption of red meat, especially fried and/or well-done red meat, was associated with increased risk of lung cancer.