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Cardiorespiratory fitness and lung cancer risk: A prospective population-based cohort study

      Abstract

      Objectives

      Little is known about the role of cardiorespiratory fitness (CRF) and leisure-time physical activity (LTPA) with the risk of lung cancer. Previous research shows that maintaining a sufficient amount of physical activity may have a protective effect against cancer. The aim of this study is to examine the associations of CRF, LTPA and lung cancer among middle-aged Finnish men.

      Design

      Prospective cohort study.

      Methods

      In a population-based cohort study of 2305 men from Eastern Finland with no history of cancer at baseline. CRF and LTPA data was collected at baseline, 73 cases of lung cancer occurred during an average follow-up of 20-years.

      Results

      In a multivariate adjusted model, every 3.8 mL/kg/min (1 SD) increase of CRF was related to a 31% decrease in lung cancer risk across all VO2max quartiles. Furthermore, a 2.8-fold (95% CI 1.14–7.22, p = 0.024) increased risk of lung cancer among men in the lowest quartile (≤20.3 mL/kg/min) of CRF as compared those in the highest quartile (>35.1 mL/kg/min). In a multivariate adjusted model LTPA was not associated to lung cancer.

      Conclusions

      In middle-aged men with no history of lung cancer, increasing levels of CRF serves as a protective factor against lung cancer. Increasing CRF may reduce the risk of lung cancer. Furthermore, CRF is a better predictor of lung cancer than LTPA.

      Keywords

      1. Introduction

      Lung cancer is the leading cause for cancer mortality worldwide.

      World Health Organization (WHO). Cancer. Available at: http://www.who.int/mediacentre/factsheets/fs297/en/ [accessed 7.10.13].

      According to the World Health Organization,

      World Health Organization (WHO). Cancer. Available at: http://www.who.int/mediacentre/factsheets/fs297/en/ [accessed 7.10.13].

      30% of cancers could be avoided due to healthier lifestyles. Previous cohort studies have reported an inverse relationship between physical activity and lung cancer risk.
      • Tardon A.
      • Lee W.J.
      • Delgado-Rodriguez M.
      • et al.
      Leisure-time physical activity and lung cancer: a meta-analysis.
      On the basis of existing evidence, 30 min of moderate physical activity on preferably all days of the week is recommended for the prevention of chronic diseases and disability.
      • Haskell W.L.
      • Lee I.M.
      • Pate R.R.
      • et al.
      Physical activity and public health: updated recommendation for adults from the American College of Sports Medicine and the American Heart Association.
      Regular physical activity has been associated with reduced risk in lung cancer.
      • Thune I.
      • Lund E.
      The influence of physical activity on lung-cancer risk. A prospective study of 81,516 men and women.
      However, the lack of association between physical activity and lung cancer has not been thoroughly investigated.
      • Batty G.D.
      • Shipley M.J.
      • Marmot M.
      • et al.
      Physical activity and cause-specific mortality in men: further evidence from the Whitehall study.
      • Wannamethee S.G.
      • Shaper A.G.
      • Walker M.
      Physical activity and risk of cancer in middle-aged men.
      Inconsistent findings may be due to measurement errors associated with self-reported physical activity. The subjective nature of self-reported physical activity may exaggerate or understate physical activity and sedentary time.
      • Ainsworth B.
      • Cahalin L.
      • Buman M.
      • et al.
      The current state of physical activity assessment tools.
      In this study, we estimated energy expenditure (EE) of Finnish men during leisure-time physical activity (LTPA).
      Little is known about the relationship of cardiorespiratory fitness (CRF) and lung cancer risk, although, there are previous reports on CRF and lung cancer mortality.
      • Sui X.
      • Lee D.-C.
      • Matthews C.
      • et al.
      Influence of cardiorespiratory fitness on lung cancer mortality.
      • Jones L.W.
      • Watson D.
      • Herndon J.E.I.I.
      • et al.
      Peak oxygen consumption and long-term all-cause mortality in nonsmall cell lung cancer.
      When comparing men with high and low CRF, Sui et al. reports a 57% reduction in lung cancer mortality.
      • Sui X.
      • Lee D.-C.
      • Matthews C.
      • et al.
      Influence of cardiorespiratory fitness on lung cancer mortality.
      Cardiorespiratory fitness is determined by the circulatory, respiratory and muscular systems ability to support the oxygen demands of physical activity. Maximal oxygen uptake (VO2max) is considered to be the gold standard for measuring CRF.
      • Taylor H.L.
      • Buskirk E.
      • Henschel A.
      Maximal oxygen intake as an objective measure of cardio-respiratory performance.
      Maximal oxygen uptake is dependent on physical activity exposure; however, age, gender, body size and genetics will influence CRF.
      • Fletcher G.F.
      • Balady G.J.
      • Amsterdam E.A.
      • et al.
      Exercise standards for testing and training: a statement for healthcare professionals from the American Heart Association.
      The aim of the present study is to investigate physical fitness versus physical activity in predicting lung cancer risk. Furthermore, we elucidate the predictability of CRF and LTPA.

      2. Materials and methods

      The subjects were a part of the Kuopio Ischemic Heart Disease Risk Factor Study. This study was designed to examine several risk factors which include CRF, atherosclerotic CVD and cancers.
      • Laukkanen J.A.
      • Pukkala E.
      • Rauramaa R.
      • et al.
      Cardiorespiratory fitness, lifestyle factors and cancer risk and mortality in Finnish men.
      This population-based cohort was a randomly selected sample of 2305 men from eastern Finland with no history of cancer. These men resided in the town of Kuopio or the surrounding communities. Baseline examinations were conducted from March 20, 1984 to December 5, 1989.
      • Kurl S.
      • Laukkanen J.A.
      • Rauramaa R.
      • et al.
      Cardiorespiratory fitness and the risk for stroke in men.
      The Research Ethics Committee of the University of Kuopio has previously approved for the study protocol in this research. Every participant gave written informed consent.
      Cardiorespiratory fitness is described as the highest value or plateau of directly measured maximal oxygen consumption by a respiratory gas analyzer.
      • Toriola A.T.
      • Laukkanen J.A.
      • Kurl S.
      • et al.
      Prediagnostic circulating markers of inflammation and risk of prostate cancer.
      The Mijnhardt Oxycon 4 analyzer expressed the maximal oxygen uptake as the average of values recorded over a 30-s period, whereas the MGC 2001 analyzer expressed it as the average of values recorded over 8 s. The mean maximal oxygen uptake was 2.4 L/min when measured with the Mijnhardt Oxycon 4 analyzer and 2.6 L/min when measured with the MGC 2001 analyzer. Pearson's coefficient for the correlation between simultaneous Mijnhardt Oxycon 4 and MGC 2001 measurements in 13 men was 0.97, indicating a close correlation.
      • Lakka T.A.
      • Venäläinen J.M.
      • Rauramaa R.
      • et al.
      Relation of leisure-time physical activity and cardiorespiratory fitness to the risk of Acute Myocardial infarction in men.
      A maximal symptom-limited exercise tolerance test was performed between 8:00 a.m. and 10:00 a.m. using an electrically braked cycle ergometer. The standardized testing protocol comprised an increase in the workload of 20 W/min. The tests were supervised by an experienced physician with the assistance of an experienced nurse.
      • Jones L.W.
      • Watson D.
      • Herndon J.E.I.I.
      • et al.
      Peak oxygen consumption and long-term all-cause mortality in nonsmall cell lung cancer.
      The common reasons for stopping the exercise of (1838) men; included leg fatigue (1163 men), exhaustion (356), breathlessness (202), pain in the leg muscles, joints or back (117). The discontinuation of the test from cardiorespiratory symptoms or abnormalities of (361) men, included arrhythmias (69), dyspnea (108), systolic or diastolic blood pressure (51), dizziness (14), chest pain (84) and ischemic electrocardiographic changes (35).
      Leisure-time physical activity was assessed using the 12-month physical activity questionnaire. This questionnaire included the most common physical activities (walking, jogging, swimming, skiing, etc.) of middle-aged Finnish men. For every physical activity, the subjects were required to indicate the frequency (sessions per month), average duration (hours and minutes per session) and intensity (0 no activity, 1 conditioning, 2 brisk, and 3 competitive). The subjects whom regularly smoked cigarettes, cigars or a pipe within the last 30 days were considered a smoker. The daily frequency and duration in years were recorded on a self-administered questionnaire which was checked by an interviewer. An estimation of lifelong exposure to smoking was determined by the number of smoking years and daily use of tobacco products.
      • Toriola A.T.
      • Kurl S.
      • Dyba T.
      • et al.
      The impact of alcohol consumption on the risk of cancer among men: a 20-year follow-up study from Finland.
      The family history of cancer is determined whether the immediate family members including father, mother, sister or brother, have previously had, or currently have cancer. Alcohol consumption was determined by the quantity and frequency method for the Nordic alcohol consumption inventory. Frequency, quantity (dose), and type of drink recording onto a response form. This assessment alcohol intake and drinking patterns are then averaged into a weekly intake, based on the alcohol content of the drink and reported doses and frequencies.
      • Toriola A.T.
      • Laukkanen J.A.
      • Kurl S.
      • et al.
      Prediagnostic circulating markers of inflammation and risk of prostate cancer.
      Food and nutrient assessment was taken at baseline by blood sampling the subjects. Dietary food and nutrient intake was calculated using the NUTRICA software, which used the quantitative recording of 4 days of data collection. NUTRICA is capable of determining the vitamins in fruits and vegetables.
      • Toriola A.T.
      • Laukkanen J.A.
      • Kurl S.
      • et al.
      Prediagnostic circulating markers of inflammation and risk of prostate cancer.
      Socioeconomic status was measured as a summary index, which includes education level, occupation, occupational prestige, material stand of living and housing conditions.
      • Toriola A.T.
      • Kurl S.
      • Dyba T.
      • et al.
      The impact of alcohol consumption on the risk of cancer among men: a 20-year follow-up study from Finland.
      Education level was examined, which was determined on the basis of lifetime education. Participants were classified into four categories; less than elementary education, completion of elementary school, completion of middle school and completion of high school or above.
      • Wilson T.W.
      • Kaplan G.A.
      • Kauhanen J.
      • et al.
      Association between plasma fibrinogen concentration and five socioeconomic indices in the Kuopio ischemic heart disease risk factor study.
      Since 1953, all of the cancer cases diagnosed in Finland are reported to the Finnish Cancer Registry (FCR). Finnish personal identification number (PID) is given to all Finnish residents. FCR has access to virtually all follow-up data on cancer diagnosis. Therefore, cancer incidence over follow-up is automatically recorded through the participants PID. There was no loss to follow-up. Follow-up started at baseline and ended on 31 Dec 2011.
      Cardiorespiratory fitness, measured as VO2max was associated to the risk factors for lung cancer by covariate analyses and the risk for lung cancer by Cox proportional hazard modeling. The VO2 max was entered as a continuous variable and classified into quartiles. Three sets of covariates were used: (1) age and examination year, (2) model 1 and cigarette smoking, alcohol consumption, and cancer in family and (3) model 1 + 2 and education, fruits and vegetables. In additional Cox models VO2max were categorized into quartiles to predict risk. The association of conventional risk factors and the risk for lung cancer was analyzed using proportional hazards Cox model. Relative hazards which were adjusted for risk factors were estimated as antilogarithms of coefficients from multivariable models. All tests for statistical significance was defined as p-values of <0.05 were 2-sided. Statistical analysis was performed by using SPSS software, version 19.0 for Windows (SPSS, Inc, Chicago, Illinois).

      3. Results

      At baseline, the mean age was 52.8 years (range 42–61years). The mean CRF was 30.2 mL/kg/min (range 6.4–65.4 mL/kg/min) and LTPA 139.9 kcal/day (range 0.01–2492.7 kcal/day). The baseline characteristics are shown in (Table 1). Men with lung cancer had lower CRF, years of education and BMI. However, they were older in age, consumed more alcohol, less of fruits and vegetables, and 84% of them were smokers. There were 73 events of lung cancer during an average follow-up of 20-years (Table 1).
      Table 1Baseline characteristics of 2305 men from Eastern Finland whom were followed for an average of 20-years.
      NWithout lung cancer, mean (SD)Lung cancer, mean (SD)p Value
      223273
      Age52.78 (5.08)54.58 (4.33)0.003
      VO2max
      VO2max: maximal oxygen uptake; LTPA: leisure-time physical activity.
      (mL/kg/min)
      30.32 (8.02)27.09 (6.74)0.001
      LTPA
      VO2max: maximal oxygen uptake; LTPA: leisure-time physical activity.
      EE (kcal/day)
      140.36 (173.14)125.85 (214.52)0.485
      Total duration (h/year)389.92 (349.02)482.13 (582.55)0.183
      Total duration (h/week)7.49 (6.71)9.27 (11.20)0.183
      Smoking (cig/day)5.01 (9.50)17.69 (12.79)<0.001
      Alcohol (g/week)71.5 (110.84)135.04 (288.10)<0.001
      Years of education8.72 (3.49)7.82 (3.30)0.030
      Fruit and berries intake 4 days, g164.31 (145.75)108.75 (116.95)0.001
      Vegetable intake 4 days (g)290.84 (125.72)250.88 (96.58)0.007
      Body mass index (kg/m2)26.89 (3.47)25.95 (3.49)0.023
      Cancer in family (%)24320.167
      Data are means and standard deviations (SD).
      p Value = t-test equality of means.
      a VO2max: maximal oxygen uptake; LTPA: leisure-time physical activity.
      In the fully adjusted model 3, the strongest risk factors included the CRF (p = 0.02), smoking (p < 0.001) and age (p = 0.05) (Table 1). Men with VO2max of ≥35.1 mL/kg/min (referent) had a 31% reduced risk of lung cancer when compared to men with VO2max of <25.0 mL/kg/min (lowest quartile). Low CRF <25.0 mL/kg/min (lowest quartile) was associated with 4.3-fold risk of lung cancer after adjustment for age and examination year (Table 2). After further adjustment for cigarette smoking, alcohol consumption, and cancer in family, the respective risk was 3-fold among men in the lowest quartile of CRF. Excluding lung cancer events in the first 2 years of follow-up, there was no affect on association of results. The Kaplan–Meier curve on the basis of quartiles is shown in Fig. 1.
      Table 2Leisure-time physical activity, maximal oxygen uptake and risk of lung cancer.
      Model 1
      Model adjusted for age and date of examination year.
      Model 2
      Model adjusted for age, date of examination year, cancer in family, smoking (cig/years), and alcohol.
      Model 3
      Model fully adjusted for age, date of examination year, cancer in family, smoking (cig/years), education, alcohol, fruits and vegetable intake. VO2max: maximal oxygen uptake.
      No. of cases
      RR (95% CI), p ValueRR (95% CI), p ValueRR (95% CI), p ValueN
      Quartiles of LTPA mean (kcal/day)
      Q4 (Ref) 367.4 (>187.4–2492.6)1 (referent)1 (referent)1 (referent)10
      Q3 (−75%) 127.4 (>83.42–186.9)1.83 (0.84–3.96), p = 0.121.65(0.63–2.96), p = 0.201.72 (0.78–3.77), p = 0.1718
      Q2 (−50%) 54.09 (>29.31–83.34)2.01 (0.94–4.30), p = 0.071.37 (0.63–2.96), p = 0.421.34 (0.62–2.89), p = 0.4520
      Q1 (−25%) 10.67 (0.00–29.25)2.60 (1.24–5.40), p = 0.011.66 (0.79–3.49), p = 0.171.56 (0.73–3.30), p = 0.2425
      Quartiles of VO2max mean (mL/kg/min)
      Q4 (Ref) 40.49 (>35.12–65.40)1 (referent)1 (referent)1 (referent)6
      Q3 (−75%) 32.48 (>30.03–35.10)3.45 (1.39–8.56), p = 0.0073.04 (1.22–7.56), p = 0.012.91 (1.17–7.23), p = 0.0222
      Q2 (−50%) 27.63 (>25.05–30.02)2.96 (1.17–7.50), p = 0.0202.48 (1.00–6.25), p = 0.052.30 (0.91–5.82), p = 0.0719
      Q1 (−25%) 20.28 (6.36–25.03)4.36 (1.75–10.80), p = 0.0012.97 (1.18–7.45), p = 0.022.88 (1.14–7.22), p = 0.0226
      * Model adjusted for age and date of examination year.
      ** Model adjusted for age, date of examination year, cancer in family, smoking (cig/years), and alcohol.
      *** Model fully adjusted for age, date of examination year, cancer in family, smoking (cig/years), education, alcohol, fruits and vegetable intake.VO2max: maximal oxygen uptake.
      Figure thumbnail gr1
      Fig. 1Multivariate adjusted model for lung cancer incidence during an average follow-up of 20 years, according to quartiles of VO2max (Q1 < 25.03 mL/kg/min (26 events), Q2 = 25.05–30.02 mL/kg/min (19 events), Q3 = 30.03–35.10 mL/kg/min) (22 events), (referent), Q4 > 35.12–65.40 mL/kg/min) (6 events).
      After adjustment for age and examination year, LTPA was statistically significant in the lowest quartile 10.67 (kcal/day) (RR 2.6) as shown in Table 2. In a multivariate adjusted model the strongest risk factors included smoking (p < 0.001), alcohol consumption (p = 0.047) and age (p = 0.011). LTPA was not associated with the risk of lung cancer. After further adjustment for model 2, every 0.80 kcal/day (1 SD) increase in LTPA had relatively no change (RR 1.04, 95% CI 0.82 to 1.30) in lung cancer risk. When adding both CRF and LTPA into a multivariate model, CRF was a significant predictor for lung cancer, whereas, LTPA was not associated to the risk of lung cancer.

      4. Discussion

      In this prospective population based study, our results show that CRF is a strong predictor of lung cancer. A standard deviation increase of 3.8 mL/kg/min of VO2max was associated with a 31% risk reduction in lung cancer. Leisure-time physical activity was not associated with lung cancer risk. CRF is a stronger predictor of lung cancer than LTPA.
      To our knowledge this is the first study where both CRF and LTPA were investigated to predict the risk of lung cancer. Previous studies on lung cancer mortality and CRF showed that among subjects with good CRF, there was a 57% risk reduction when compared to poor CRF.
      • Sui X.
      • Lee D.-C.
      • Matthews C.
      • et al.
      Influence of cardiorespiratory fitness on lung cancer mortality.
      Another study observed a risk reduction in lung cancer mortality with increased CRF. They found that higher VO2peak categories had a 21% to 25% risk reduction in lung cancer mortality when compared to lower categories.
      • Jones L.W.
      • Watson D.
      • Herndon J.E.I.I.
      • et al.
      Peak oxygen consumption and long-term all-cause mortality in nonsmall cell lung cancer.
      These two studies show an inverse relationship between higher levels of CRF and lung cancer mortality.
      In our study no association was observed between LTPA and lung cancer risk. A previous study on physical activity reported a risk reduction in lung cancer among physically active individuals. Cardiorespiratory fitness and LTPA may provide different associations of risk for predicting health and disease outcomes. Similar to previous reports, our study supports the sensitivity of CRF for predicting cancer outcomes.
      • Kaminsky L.A.
      • Arena R.
      • Beckie T.M.
      • et al.
      The importance of cardiorespiratory fitness in the United States: the need for a national registry. A policy statement from the American Heart Association.
      Our study shows the objective measure of CRF had a stronger association with lung cancer risk than the subjective measure of LTPA. These differences are likely due to the physiological component of CRF. Cardiorespiratory fitness is capable of estimating physical activity exposure more accurately than a questionnaire-based LTPA. The LTPA questionnaire included common physical activities (walking, jogging, swimming, etc.) of middle-aged Finnish men. The most important factors effecting CRF include age, gender, BMI, and physical activity.
      • Lakoski S.G.
      • Barlow C.E.
      • Farrell S.W.
      • et al.
      Impact of body mass index, physical activity, and other clinical factors on cardiorespiratory fitness (from the cooper center longitudinal study).
      Cardiorespiratory fitness was defined as VO2max, based on directly measured by respiratory gas analyses.
      Generally, a limitation of studies based on physical activity and cancer may be due to the lag time between preclinical cancer and cancer.
      • Paffenbarger Jr., R.S.
      • Hyde R.T.
      • Wing A.L.
      • et al.
      The association of changes in physical-activity level and other lifestyle characteristics with mortality among men.
      Although, a protective effect of physical activity could prolong this lag time from preclinical tumor to cancer.
      • McTiernan A.
      • Schwartz R.S.
      • Potter J.
      • et al.
      Exercise clinical trials in cancer prevention research: a call to action.
      This protective effect of physical activity may be due to the improved immune system function, by increasing natural killer cells.
      • Shepard R.J.
      • Shek P.N.
      Associations between physical activity and susceptibility to cancer possible mechanisms.
      Physical training may improve monocytes, macrophages and natural killer cells, these non-specific immune systems have protective effects from malignancies.
      • Kiningham R.B.
      Physical activity and primary prevention of cancer.
      Additional benefits of physical activity in cancer prevention may include appropriate body mass, hormonal levels and healthy energy balance.
      • Thune I.
      Cancer, 19, physical activity in the prevention and treatment of disease, professional associations for physical activity (Sweden).
      Previous reports of heavy smokers who appeared healthy, have significantly lower VO2max than that of non-smoking healthy subjects.
      • Tzani P.
      • Aiello M.
      • Colella M.
      • et al.
      Lung diffusion capacity can predict maximal exercise in apparently health heavy smokers.
      Furthermore, smoking has been shown to have a negative impact on aerobic endurance.
      • Misigoj-Durakovic M.
      • Bok D.
      • Soric M.
      • et al.
      The effect of cigarette smoking history on muscular and cardiorespiratory endurance.
      These reports suggest that smoking could increase lung cancer risk, in part, by decreasing CRF. Our results share similar characteristics, whereas, lung cancer was common among smokers and lower CRF.
      In a meta-analysis of smoking and lung cancer, previous studies have shown an association of smoking to all types of lung cancer.
      • Khuder S.A.
      Effect of cigarette smoking on major histological types of lung cancer: a meta-analysis.
      In our study cohort 32% were smokers and 84% of the smokers had developed lung cancer. Consistent with our study, a previous report suggests that less than 20% of smokers contracted lung cancer.
      • Hect S.S.
      Cigarette smoking and lung cancer: chemical mechanisms and approaches to prevention.
      Leitzmann et al. examined current, former and never smokers in a large prospective study of middle-aged men and women.
      • Leitzmann M.F.
      • Koebnick C.
      • Abnet C.C.
      • et al.
      Prospective study of physical activity and lung cancer by histologic type in current, former and never smokers.
      The biological mechanisms may include; time reduction for carcinogenic effects by increased pulmonary ventilation and perfusion. Additionally, by increasing the lung function/capacity, this may impede smoking-related declines in lung function, which is recognized as a predictor of lung cancer.
      • Leitzmann M.F.
      • Koebnick C.
      • Abnet C.C.
      • et al.
      Prospective study of physical activity and lung cancer by histologic type in current, former and never smokers.
      A recent meta-analysis has shown that moderate to high levels of physical activity are associated with reduced lung cancer risk among smokers.
      • Buffart L.M.
      • Singh A.S.
      • van Loon E.C.
      • et al.
      Physical activity and the risk of developing lung cancer among smokers: a meta-analysis.
      The strengths of this study include the prospective population study design, the reliability of anthropometric measures, reliable lung cancer diagnosis and detailed assessment of risk factors. Additionally, we have a long follow-up period of 20-years in middle-age men with exclusion of all men with history of cancer at baseline. Our study has some limitations. First, lifestyle factors which include physical activity and genetic susceptibility may interact in the etiology of cancers. This may limit the ability to show how one factor can independently contribute to risk reduction. Second, the physical activity measure of self-report may be subject to misclassification. Third, the study subjects were middle-aged men from eastern Finland, further investigations may include women or other ethnic groups. Lastly, the genetic component of CRF is about 70% but CRF can be improved to some extent with the help of physical activity.

      5. Conclusion

      This prospective study indicates that CRF is inversely and independently associated with the risk of lung cancer. In lung cancer prevention, methods for improving CRF may limit risks more effectively than LTPA. The intensity of LTPA was not associated with the risk of lung cancer. Our results show that CRF is a better predictor of lung cancers.

      Practical implications

      • Our study shows that cardiorespiratory fitness is a strong predictor of lung cancer. We describe how cardiorespiratory fitness can predict lung cancer, and serves as stronger measure than leisure-time physical activity in predicting lung cancer.
      • This study adds broader recognition in the value of cardiorespiratory fitness. This study recognizes that questionnaires and cardiorespiratory fitness estimation is common in population data collection. Questionnaires were used for leisure time physical activity to estimate estimated energy expenditure and cardiorespiratory fitness was measured using VO2max with gas analysis.
      • This study shows that directly measured cardiorespiratory fitness is a better predictor of lung cancer risk than leisure-time physical activity in a long-term follow-up period.

      Funding statement

      This research was not supported by any funding agency.

      Acknowledgements

      The authors would like to thank the staff from the Institute of Public Health and Clinical Nutrition at the University of Eastern Finland and the Kuopio Research Institute of Exercise Medicine for the data collection.

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