29-06-2012, 11:57 AM
Influence of Cardiorespiratory Fitness on Lung Cancer Mortality
Influence of Cardiorespiratory Fitness on Lung Cancer Mortality.docx (Size: 259.39 KB / Downloads: 164)
Abstract
Purpose: Previous studies have suggested that higher levels of physical activity may lower lung cancer risk; however, few prospective studies have evaluated lung cancer mortality in relation to cardiorespiratory fitness (CRF), an objective marker of recent physical activity habits.
Methods: Thirty-eight thousand men, aged 20–84 yr, without history of cancer, received a preventive medical examination at the Cooper Clinic in Dallas, Texas, between 1974 and 2002. CRF was quantified as maximal treadmill exercise test duration and was grouped for analysis as low (lowest 20% of exercise duration), moderate (middle 40%), and high (upper 40%).
Results: A total of 232 lung cancer deaths occurred during follow-up (mean = 17 yr). After adjustment for age, examination year, body mass index, smoking, drinking, physical activity, and family history of cancer, hazard ratios (95% confidence intervals) for lung cancer deaths across low, moderate, and high CRF categories were 1.0, 0.48 (0.35–0.67), and 0.43 (0.28–0.65), respectively. There was an inverse association between CRF and lung cancer mortality in former (P for trend = 0.005) and current smokers (P for trend < 0.001) but not in never smokers (trend P = 0.14). Joint analysis of smoking and fitness status revealed a significant 12-fold higher risk of death in current smokers (hazard ratio = 11.9, 95% confidence interval = 6.0–23.6) with low CRF as compared with never smokers who had high CRF.
Conclusions: Although the potential for some residual confounding by smoking could not be eliminated, these data suggest that CRF is inversely associated with lung cancer mortality in men. Continued study of CRF in relation to lung cancer, particularly among smokers, may further our understanding of disease etiology and reveal additional strategies for reducing its burden.
Introduction
Physical inactivity is associated with an increased overall risk of cancer mortality[17] and mortality associated with specific anatomic sites such as colon[31] and breast.[14] However, there is little information regarding the association of inactivity and lung cancer, which is the most common cause of cancer death in the United States. According to the most recent report from the American Cancer Society, in 2009, an estimated 116,090 new cases of lung cancer will be diagnosed, and approximately 88,900 men are expected to die from this disease.[3] Cigarette smoking is the most important cause of lung cancer. Still, many nonsmokers die of the disease, and former smokers remain at elevated risk after quitting. It is estimated that in the United States alone, about 3000 lung cancer deaths occur each year in nonsmoking adults.[3] It takes up to 20 yr for a majority of former smokers' rates to drop to those of never smokers.[19] Therefore, it is plausible that other factors besides smoking may play an important etiologic role. Moreover, the majority of cigarette smokers do not develop lung cancer, and this fact adds to the likelihood that there may be other factors besides smoking that modify risk. One of these other factors might be physical activity.
Most previous cohort studies[2,5,9,12,20,21,26,32,34,39] have reported an inverse association between risk of lung cancer and physical activity in men; however, some have not.[7,11,25,30,33,43] These inconsistent findings may be due partly to the measurement errors inherent in self-reported physical activity. Cardiorespiratory fitness (CRF), an objective and a more reproducible measure that reflects the functional consequences of physical activity habits, may provide a better exposure with which to evaluate associations with lung cancer risk. To the best of our knowledge, only one study[38] has been conducted on CRF and lung cancer mortality among men. However, this study examined only men with prediabetes and diabetes. To address cancer prevention strategies, it is important to investigate whether physical activity or CRF reduces cancer incidence or mortality in the general population prospectively. The objective of this report is to examine the risk of lung cancer mortality across levels of fitness, obtained by maximal exercise test on a treadmill, in a large cohort of men from the Aerobics Center Longitudinal Study (ACLS).[17]
Methods
Study Population
The ACLS is a prospective study composed of patients who received preventive medical examinations at the Cooper Clinic in Dallas, Texas. The current analysis included 38,000 men ranging in age from 20 to 84 yr who completed a clinical examination, including fitness testing, between 1974 and 2002 with mortality follow-up through December 31, 2003. Men with any physician-diagnosed cancer or those unable to complete an exercise stress test to at least 85% of their age-predicted maximal heart rate (220 minus age in years) were excluded. Women also were excluded from this analysis because of limitations in sample size and, concomitantly, lung cancer deaths. Most participants were white (>95%) and employed or previously employed in professional occupations. This study was reviewed and approved annually by the Cooper Institute institutional review board.
Baseline Examination
Participants provided written informed consent to participate in the examination and follow-up study. All medical evaluations included personal and family histories, questionnaire on demographic characteristics and health habits, physical examination, anthropometry, electrocardiogram, blood chemistry analyses, blood pressure measurements, and maximal exercise test on a treadmill. The comprehensive medical evaluation is described in detail elsewhere.[17,38] Briefly, body mass index (BMI) was calculated as measured weight in kilograms divided by height in meters squared. On the basis of self-reported current and past smoking behavior, participants were categorized into one of three groups: those who currently smoked cigarettes (current smokers), those who previously smoked cigarettes (former smokers), and those who never smoked cigarettes (never smokers). Number of cigarettes smoked, year started smoking, and year quitting smoking were used to calculate pack-years. To measure alcohol use, one unit of alcohol was defined as 12 oz (3.41 dL) of beer, 5 oz (1.421 dL) of wine, or 1.5 oz (0.4262 dL) of hard liquor. Physically inactive was defined as reporting no leisure-time physical activity such as walking, jogging, running, treadmill exercise, cycling, stationary cycling, swimming, racquet sports, aerobic dance, or other sports-related activities (e.g., basketball or soccer) in the 3 months before the baseline examination. Family history (from parents and siblings; first-degree relatives) of cancer was obtained from a standardized questionnaire.
Pulmonary function assessment was performed in a subset of the participants (79% of the total study sample), and forced expiratory volume in 1 s (FEV1) was obtained with a Collins 421 Survey spirometer (Collins, MA), as described elsewhere.[8] All procedures were administered by trained technicians who followed standardized protocols. Hankinson et al.[13] derived predictive equations for FEV1 specific for sex, age, and height and derived from healthy participants of the Third National Health and Nutrition Examination Survey. The FEV1 was expressed both as raw values and as a percentage of the predictive values.
We determined CRF using a modified Balke maximal exercise test, as described in previous publications.[6,17] The treadmill speed was 88 m•min−1 for the first 25 min. During this time, the grade was 0% for the first minute and 2% for the second minute and increased 1% each minute until 25 min had elapsed. After 25 min, the grade remained constant while the speed increased 5.4 m•min−1 each minute until test termination. Patients were encouraged to give a maximal effort during the test. The mean (SD) percentage of age-predicted maximal heart rate achieved during exercise was 101.5 (6.6). Total time of the test correlates highly (r = 0.92) with measured maximal oxygen uptake.[23] Thus, CRF in this study is analogous to maximal aerobic power. METs (1 MET = 3.5 mL O2 uptake per kilogram per minute) were estimated from the final treadmill speed and grade.[4] We assigned men to age-specific fitness categories on the basis of their total time on the treadmill test. We classified the lowest 20% as low fit, the next 40% of the fitness distribution as moderately fit, and the upper 40% as high fit, as in our previous reports, on the basis of data from the entire cohort. The detailed cut points of treadmill duration and corresponding MET values have been reported earlier.[36]