Showing papers by "Arthur Schatzkin published in 1990"

Body Fat Distribution and Breast Cancer in the Framingham Study

Abstract: We examined the relation between central body fat distribution and breast cancer in a prospective cohort of women who participated in the Framingham Study. At the baseline examination in 1948, a total of 2,201 women aged 30-62 years were analyzed. An index of central to peripheral body fat (the central adiposity ratio) was calculated from the sum of the trunkal skinfolds (chest, subscapular, and abdominal) divided by the sum of the extremity skinfolds (triceps and thigh). These skinfolds were measured at the fourth examination in 1954. The cohort was followed for up to 28 years and yielded 106 cases of breast cancer. When divided into quartiles based on the central adiposity ratio, only women in the fourth quartile (those with the highest central to peripheral body fat distribution) demonstrated an increased risk for breast cancer. The age- and adiposity-adjusted relative risk estimate for having an increased central adiposity ratio (fourth quartile) compared to lower central adiposity ratios was 1.8 (95% confidence interval, 1.2-2.6). Adjustment for potential confounders of height, parity, and education did not appreciably alter this estimate (1.7, 1.1-2.5). There was no association between degree of adiposity, as measured by the sum of the five skinfolds or by body mass index (weight in kg divided by height in m2), and subsequent breast cancer. The results of this study suggest that increased central to peripheral body fat distribution predicts breast cancer risk independently of the degree of adiposity and may be a more specific marker of a premalignant hormonal pattern than degree of adiposity.

Validation of Intermediate End Points in Cancer Research

Abstract: Investigations using intermediate end points as cancer surrogates are quicker, smaller, and less expensive than studies that use malignancy as the end point. We present a strategy for determining whether a given biomarker is a valid intermediate end point between an exposure and incidence of cancer. Candidate intermediate end points may be selected from case series, ecologic studies, and animal experiments. Prospective cohort and sometimes case-control studies may be used to quantify the intermediate end point-cancer association. The most appropriate measure of this association is the attributable proportion. The intermediate end point is a valid cancer surrogate if the attributable proportion is close to 1.0, but not if it is close to 0. Usually, the attributable proportion is close to neither 1.0 nor 0; in this case, valid surrogacy requires that the intermediate end point mediate an established exposure-cancer relation. This would in turn imply that the exposure effect would vanish if adjusted for the intermediate end point. We discuss the relative advantages of intervention and observational studies for the validation of intermediate end points. This validation strategy also may be applied to intermediate end points for adverse reproductive outcomes and chronic diseases other than cancer.

Physical Activity and Risk of Large Bowel Cancer in the Framingham Study

Abstract: We examined the relation between self-reported physical activity and large bowel cancer in a prospective cohort of men and women who participated in the Framingham Study. Self-assessments of physical activity were available from the fourth biennial examination on a total of 1906 men and 2308 women aged 30 to 62 yr in 1954. The cohort was followed for up to 28 yr and yielded 152 cases (73 men, 79 women) of large bowel cancer. Inactivity was associated with an increased risk of large bowel cancer among men but not among women. The relative risk estimates for large bowel cancer among men in the middle and lowest tertiles of a physical activity index (compared with the highest tertile) were 1.4 (95% confidence intervals, 0.8-2.6) and 1.8 (1.0-3.2), respectively. Among women the comparable estimates were 1.2 (0.7-2.1) and 1.1 (0.6-1.8), respectively. These findings were unchanged after adjustment for body mass index, serum cholesterol, alcohol, and other potentially confounding variables. The narrow range of physical activity and the minimal heavy activity reported by women in this cohort may have limited our ability to detect an association between physical activity and large bowel cancer among women.

Quantitative Evaluation of the Radon and Lung Cancer Association in a Case Control Study of Chinese Tin Miners

Abstract: Studies of underground miners have consistently shown an increased risk of lung cancer with cumulative exposure to radon-222 and its decay products. Although the deleterious effects of high radon exposure are clear, questions regarding the shape of the exposure-response relationship, and the effects of time factors such as attained age, time since exposure and early age at first exposure, the effect of exposure rate, and the joint association of radon exposure and tobacco use have not yet been fully clarified. This report considers these questions by fitting various models for the relative odds of disease to 74 male lung cancer cases who were diagnosed between 1981 and 1984 and were alive in 1985 and an equal number of controls. All subjects are current or past employees of the Yunnan Tin Corporation, Gejiu City, China, who reside in the local area. Workers were interviewed to obtain information on work history, from which radon exposure in cumulative working level months and arsenic exposure were estimated, and on tobacco use. Results indicate that excess relative risk increases by 1.7% per cumulative working level month [95% confidence interval (0.5, 5.4)]. The linear exposure response relationship significantly declines with year since last radon exposure (P = 0.02). The risk trend also declines with increasing exposure rate (P = 0.001), indicating that long duration of exposure at a low rate may be more deleterious than short duration of exposure at a high rate. A unique aspect of this study population is the very early ages at first radon exposure for many of the workers, about 37% of the radon-exposed workers were first exposed under the age of 13 years. The analysis shows no modification of the radon lung cancer relationship with age at first exposure. These patterns of risk with radon exposure are generally consistent with those reported in the recent National Academy of Sciences' Biological Effects of Ionizing Radiations IV report. The primary method of tobacco consumption in this area of China is by waterpipe. Lung cancer risk increases with pipe-years of use. The joint analysis of tobacco use and radon exposure supports the Biological Effects of Ionizing Radiations IV conclusion that the most likely model is between additive and multiplicative. The variations of the radon lung cancer relationship by years since last exposure and exposure rate are not affected by adjustment for arsenic exposure.

The impact of dietary measurement error on planning sample size required in a cohort study

Abstract: Dietary measurement error has two consequences relevant to epidemiologic studies: first, a proportion of subjects are misclassified into the wrong groups, and second, the distribution of reported intakes is wider than the distribution of true intakes. While the first effect has been dealt with by several other authors, the second effect has not received as much attention. Using a simple errors-in-measurement model, the authors investigate the implications of measurement error for the distribution of fat intake. They then show how the inference of a more narrow distribution of true intakes affects the calculation of sample size for a cohort study. The authors give an example of the calculation for a cohort study investigating dietary fat and colorectal cancer. This shows that measurement error has a profound effect on sample size, requiring a six- to eightfold increase over the number required in the absence of error, if the correlation coefficient between reported and true intakes is 0.65. Reliable detection of a relative risk of 1.36 between a true intake of greater than 47.5% calories from fat and less than 25% calories from fat would require approximately one million subjects.