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Nutrition Habits, Physical Activity, and Lung Cancer: An Authoritative Review

Clinical Lung Cancer, 4, 14, pages 342 - 350

Abstract

Lung cancer is the leading cause of cancer death worldwide. Because of high incidence rates and low survival rates, it is important to study the risk factors that may help prevent the disease from developing. It has been well established that cigarette smoking is the most important risk factor for lung cancer. Nonetheless it is likely that there are other modifiable risk factors that would assist in the prevention of lung cancer. Research on factors such as nutrition and physical activity and their influence on lung cancer has been carried out for nearly 3 decades. A systematic review in the MEDLINE database of published studies was conducted, focusing on systematic reviews, meta-analyses, and large prospective studies. The association between physical activity and lung cancer has been conflicting. Among the researched studies, 10 showed an inverse association, whereas 11 reported no association. A meta-analysis that was conducted from 1996 to October 2003 showed that leisure physical activity (LPA) prevents lung cancer. Data from 11 cohort and case-control studies showed an inverse relationship between fruit and vegetable consumption and lung cancer. Evidence from case-control studies suggests a positive association between meat intake and risk of lung cancer, although several more recent studies have presented doubts about these findings. The possible association of physical activity, nutrition, and the risk of lung cancer development remains controversial. Further prospective studies should be conducted to determine the potential influence of these 2 risk factors.

Keywords: Diet, Exercise, Lung cancer, Nutrition, Physical activity.

Introduction

Lung cancer is the leading cause of cancer death worldwide. 1 It is the second most commonly diagnosed cancer among men and women in the United States and the incidence rate increases with age. 2 Lung cancer is often diagnosed at an advanced stage; therefore available treatment results in a poor outcome. Each year in the United States, more than 200,000 new cases of lung cancer are diagnosed and nearly 150,000 individuals die of the disease. 3 Lung cancer can be divided into 4 major histologic subtypes: adenocarcinoma, small-cell carcinoma, large-cell carcinoma, and squamous cell carcinoma. Squamous cell carcinoma rates exceeded adenocarcinoma rates among male patients in all areas in earlier years, but the varying trends have narrowed the differences. In recent years, adenocarcinoma has been the predominant form of lung cancer among male patients in Iceland and the United States. Among female patients, adenocarcinoma rates have always been higher than squamous cell carcinoma rates in every area, and the differences have widened over time. 4 In men, the incidence of squamous and small-cell cancer is decreasing, whereas the incidence of adenocarcinoma is stable or increasing slightly in Western countries. For women, the incidence of all histologic subtypes is increasing, although it is most rapid for adenocarcinoma. 4 Lung cancer was a rare disease at the start of the 20th century, but exposures to new causative agents and an increasing life span combined to make lung cancer a scourge of the 20th century. Smoking is by far the most important risk factor for lung cancer, to which 85% of all cases can be attributed. 5 Tobacco smoking is related to all histologic subtypes of lung cancer, but the strength of the association differs, with small-cell carcinoma showing the strongest association followed by squamous cell carcinoma, whereas adenocarcinoma shows the weakest association with tobacco smoking. 6 Likewise, the effect of smoking cessation is strongest for small-cell carcinoma and weakest for adenocarcinoma. 7 Furthermore, given that lung cancer never develops in many smokers, it is possible that there are additional factors that may exacerbate or diminish the risk associated with smoking. Beginning in the early 1970s, associations of diet with lung cancer risk have been vigorously investigated, with the anticipation that dietary micronutrients might be found that modify the high lung cancer risk in smokers. Several studies have also evaluated the relationship between physical activity and lung cancer.

The purpose of this review was to investigate, through the current literature, the probable correlation between nutrition, physical activity, and lung cancer.

Methods

A MEDLINE (June 1989 to May 2011) search was conducted using the following terms: physical activity, exercise, nutrition, diet, and lung cancer.

Results

Physical Activity and Lung Cancer

Physical activity is a behavior defined as bodily movement produced by skeletal muscles, resulting in a quantifiable level of energy expenditure. It is associated with daily living, work, and leisure-time activities. Leisure-time physical activity (LPA) is often characterized by short-term, intensive energy expenditure, whereas occupational physical activity (OPA) is more likely to occur over longer periods (eg, hours) at lower rates of energy expenditure. 8

There are several plausible mechanisms by which physical activity may reduce the risk of lung cancer.9, 10, 11, 12, and 13 For example, physical activity improves pulmonary function, which may reduce the concentration of carcinogenic agents in the airway, reduce the duration of agent-airway interaction, and reduce the extent to which carcinogenic particles are deposited in the airways10, 11, 12, and 13; although plausible mechanisms exist, evidence regarding the association between physical activity and lung cancer has been conflicting.

Many studies have examined the association between physical activity and lung cancer risk.10, 11, 12, 13, 14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, and 30 Ten studies have shown an inverse association,10, 11, 12, 13, 14, 15, 16, 17, 18, and 19 whereas 11 others have reported no association.20, 21, 22, 23, 24, 25, 26, 27, 28, 29, and 30

Most of these studies included only men.12, 13, 15, 16, 18, 20, 22, 23, and 27 Of the 8 studies that examined this association in women, 4 reported independent inverse associations between physical activity and lung cancer risk, whereas the other 4 studies reported no association in women.10, 11, 14, 19, 21, 24, 25, and 26 Two of the previous null studies were limited with regard to the number of lung cancer cases, with only 51 (0.18%) and 59 (1%) cases in women, respectively.21 and 24 The third null case control study was not adjusted for smoking. 25 The fourth null study used occupational title as a surrogate measure of physical activity. 26 The association of OPA and lung cancer has been developed in 8 studies, 5 of which studied exclusively the OPA in association with lung cancer risk.16, 21, 23, 24, 26, 28, 29, and 30 All of these studies, apart from the one from Brownson et al, proved that physical activity is not associated with lung cancer risk. 16

Mao et al's case-control study was conducted to assess the impact of recreational physical activity on lung cancer risk in Canada in 1994 to 1997. A total of 2128 (68%) (1131 [36%] men and 997 [32%] women) incident lung cancer cases and 3106 population controls were included in this study. Mao et al suggested that recreational physical activity is associated with a decreased lung cancer risk for both sexes, and both moderate and vigorous levels of recreational physical activity conferred the risk reductions. They also observed greater reductions in lung cancer risk associated with total recreational physical activity for squamous cell carcinoma and other/unspecified subtypes in women and for small-cell carcinoma and other/unspecified subtypes in men. In addition, they found that recreational physical activity had a much greater protective effect against lung cancer for smokers (especially current smokers and heavy smokers) and for subgroups with low and medium body mass index (BMI). 11

Sinner et al (the most recent report) used data from the Iowa Women's Health Study (IWHS) (36,410 participants, including 777 [2%] in whom lung cancer developed) and analyzed the association of physical activity with lung cancer incidence in a cohort of older women. 19 It was a large cohort study of women who were followed for almost 20 years. This study suggested that independent of smoking status, pack-years of smoking, and other confounders, physical activity is associated with a decreased risk of lung cancer in women, and both moderate and vigorous physical activity were associated with risk reductions. Physical activity had a moderate inverse association with risk of lung cancer in current and former smokers.

Kubík et al's case control study had 419 (26.3%) patients, including 130 nonsmoking patients (never-smokers and those who quit > 20 years previously) and 1593 controls. 17 They reported that among women who smoked, those with > 6 hours/wk of physical exercise were 0.48-fold less likely to get lung cancer than those with 0 to 2 hours of activity per week. Kubík et al observed that this reduction in risk was not apparent among nonsmokers.

Alfano et al completed a study, drawn from CARET (β-Carotene and Retinol Efficacy Trial), examining physical activity and lung cancer incidence and mortality among 2878 female current or former smokers. 14 They reported no association between physical activity and lung cancer incidence. However women who were physically active were at a decreased risk of lung cancer mortality compared with women who were not physically active.

Of the studies that assessed the relationship between LPA and lung cancer risk, 5 were undertaken in the United States—National Health and Nutrition Examination Survey, Hawaii Honolulu Heart Study, IWHS, 1 in Missouri and the Harvard Alumni Study—and 6 were conducted in Europe—Norway Health Study of Cardiovascular Disease, British Regional Heart Study, 2 case-control studies in The Czech Republic, 2 studies in Finland, and 1 study in Canada (Canadian National Enhanced Cancer Surveillance System).11, 12, 13, 16, 17, 19, 21, 22, 25, 26, and 27

Lee et al's cohort study indicated that physical activity may be associated with lower risk of lung cancer among men. 12 An energy expenditure of 12,600 kJ/wk, achievable by perhaps 6 to 8 hours of at least moderate-intensity physical activity, may significantly lower the risk. This study reported that highly physically active men, whether they were nonsmokers (83%), current smokers of less than 20 cigarettes/d (8%), or current smokers of more than 20 cigarettes/d (8%) had a lower risk of lung cancer than did those who were less active. In a previous study they examined only nonsmokers (n = 9457) and found a highly significant inverse relation between activity level and lung cancer in those who had never smoked (odds ratio [OR], 0.47; 95% confidence interval [CI], 0.27-0.82). 15 Mao et al found nonsignificant inverse associations for persons who never smoked (n = 1257; OR, 0.68; 95% CI, 0.39-1.19) and for ex-smokers (n = 2061; OR, 0.75; 95% CI, 0.62-1.13). 11 They also found that fruit and vegetable intake have consistently been associated with a decreased lung cancer risk and a healthy diet may be associated with physical activity. Three other studies did adjust for possible confounding from diet.14, 17, and 27

Two other studies found inconsistent results when they tried to evaluate the relationship between LPA and lung cancer.26 and 22 Colbert et al's cohort study included only male smokers and found no association between OPA or LPA and lung cancer risk, except of a modest risk reduction among younger smokers. 27 These 3 studies classified LPA into 3 levels of intensity, ie, low (sedentary, low, or inactive), moderate (moderate, medium, or moderately vigorous), and high (frequent exercise, high, vigorous, or heavy), whereas Thune et al, Lee et al, and Mao et al used 4 intensity categories, consisting of the 3 mentioned plus an additional ”very high” category.11, 12, and 21 Thune et al and Mao et al reported results for men and women separately, but Thune et al found that LPA had a protective effect on lung cancer risk in men only, and there was no consistent association between physical activity and lung cancer risk among women.

The first meta-analysis performed on LPA and lung cancer in the literature summarized and reviewed reports published from 1966 through October 2003. This meta-analysis showed that moderate and higher levels of LPA protected against lung cancer in men and women. 31

There are several underlying biological mechanisms hypothesized for physical activity in cancer development. Exercise could affect cancer development through its impact on growth factors, such as insulin-like growth factors (IGFs) and IGF binding proteins (IGFBPs). 32 High levels of circulating IGF-1 were associated with an increased risk of lung cancer and high levels of IGFBP-3 with a decreased risk. 11 Exercise significantly lowers levels of insulin, glucose, and triglycerides and raises levels of high-density lipoprotein cholesterol, which may also be associated with decreased cancer risk. 32 Another possibility is the effect of exercise on the immune system. Immune function is enhanced with long-term exercise through increases in the number and activity of macrophages, natural killer cells, and lymphokine-activated killer cells and their regulated cytokines, as well as increased mitogen-induced lymphocyte proliferation rates.32, 33, 34, and 35 It has long been observed that immunocompromised individuals are at a higher risk for lung cancer, and moderate-intensity exercise training has been shown to improve immune function.36 and 37 Smoking and environmental respiratory exposures also result in inflammatory responses, and exercise training has been shown to attenuate these same responses.38, 39, 40, 41, 42, 43, and 44 Finally, there certainly is evidence for increased oxidative stress from both smoking and environmental exposures, and exercise training has been observed to increase endogenous free radical scavengers, even in smokers.38 and 45 Perhaps exercise training can be thought of as an incremental and controlled physiologic stress that enables the body to respond to smoking and environmental stresses more effectively. It is also possible that the increased pulmonary ventilation and perfusion from physical activity is involved. Several studies have found that airway obstruction increases lung cancer risk, so even after taking cigarette smoking into account, increased pulmonary function after high levels of physical activity could result in decreased opportunity for airway exposure to inhaled carcinogens.21 and 34

Diet and Lung Cancer

The possible role of nutrition in modifying the risk of lung cancer has been the focus of intensive investigation that has been carried out for nearly 3 decades. Much of the research on diet and lung cancer has been motivated by the hypothesis that diets high in antioxidant nutrients may reduce oxidative DNA damage and thereby protect against cancer. 46 Vegetables and fruits are known to contain numerous potentially beneficial antioxidants, fibers, minerals, and phytochemicals that may help prevent cancer and contribute to maintenance of a healthy weight. 47 Plant foods contain thousands of biologically active phytochemicals, such as isothiocyanates and flavonoids. Many of these compounds inhibit phase I carcinogen-metabolizing enzymes, induce phase II detoxification enzymes, enhance the immune system, and modulate circulating hormone concentrations. 48

Evidence from cohort studies, case-control studies, prospective studies, and a systematic review shows that individuals with high dietary intake of fruits or vegetables have a lower risk of lung cancer than do those with low fruit or vegetable intake.49, 50, 51, 52, 53, 54, 55, 56, 57, 58, and 59

A Danish cohort study that was conducted in 1993 to 2001 observed an inverse association between high intake of plant foods (fruit, vegetables, legumes, and potatoes) and lung cancer. 49 A previous cohort study (1985-1993) in Finland showed the same results, particularly that a diet rich in carotenoids, tomatoes, and tomato-based products may reduce the risk of lung cancer. 51

Wright et al's case-control study indicated that consumption of a variety of vegetables was associated with a significantly lower risk of cancer in women of the Missouri Health Study. 50

The CARET, a multicenter randomized double-blind placebo-controlled chemoprevention trial tried to test whether daily supplementation with 30 mg of β-carotene and 25,000 IU of retinyl palmitate would reduce the risk of lung cancer among 18,314 heavy smokers and asbestos-exposed workers; this study used data from 14,120 participants. After 12 years of follow-up, lung cancer had developed in 742 (5%) participants. In this large chemoprevention trial of heavy smokers, former heavy smokers, and asbestos-exposed workers, consumption of specific classes of fruits and vegetables was inversely associated with lung cancer risk only among participants who were not randomized to receive the CARET study supplements (the combination of β-carotene and vitamin A). 52

Feskanich et al's prospective study noted that both fruits and vegetables were associated with lower risks of lung cancer among women but not among men, although fruits and vegetables were protective in both men and women who never smoked. 53

The 2007 World Cancer Research Fund/American Institute for Cancer Research (WCRF/AICR) expert report does not mention differences in effect of fruit and vegetable consumption between the different histologic subtypes of lung cancer. 60 There are indications that the association of vegetables and fruits may vary among the histologic subtypes of lung cancer, but study results are inconsistent. A suggestion of a stronger inverse association for total fruit and vegetable consumption and total fruit consumption in adenocarcinomas and squamous cell carcinomas compared with small-cell carcinomas was shown in a pooled analysis of 8 prospective studies. 55

The 2007 WCRF/AICR expert report, including only the first EPIC (European Investigation into Cancer and Nutrition) publication on fruit and vegetable consumption and lung cancer risk by Miller et al, concluded that the evidence of an inverse relationship between increased fruit consumption and decreased lung cancer risk is consistent and that there is a dose-response relationship found in both cohort and case-control studies.54 and 60 The third EPIC publication is in line with these findings and found inverse associations between the consumption of vegetables and fruits combined and consumption of fruits and risk of lung cancer. This study additionally looked at fruit and vegetable consumption and the different histologic subtypes of lung cancer. This third EPIC publication by Bücher et al showed that there is no clear effect of consumption of fruit and/or vegetables on risks for specific histologic subtypes of lung cancer. 56 In current smokers, this study found that the consumption of vegetables and fruits combined and separately may reduce lung cancer risk, in particular the risk of squamous cell carcinoma.

Some cohort studies have analyzed the effect of fruits and vegetables on different histologic subtypes of lung tumors.49, 53, and 61 These studies have divided lung tumors into 2 groups; Kreyberg I (comprising small-cell carcinomas, squamous cell carcinomas, and large-cell carcinomas) and Kreyberg II (adenocarcinomas). There were indications that fruits and vegetables were more protective for nonadenocarcinomas (Kreyberg I) than for adenocarcinomas (Kreyberg II). In the study of Skuladottir et al, a protective effect was found for fruits on squamous cell carcinomas, and an inverse association was found for vegetables on small-cell carcinomas. 49 No association for the intake of fruits and vegetables and any histologic subtype of lung cancer was reported by Liu et al. 61 A protective effect of total vegetable consumption was not observed in the studies by Miller et al and Feskanich et al.53 and 54 Many studies (retrospective and prospective) have indicated a clear protective effect of fruit and vegetables on lung cancer risk among current smokers only. 55 These studies suggested that antioxidants from vegetables and fruits strongly reduce the oxidative stress caused by smoking. In contrast, others have found a stronger protective effect of fruits among nonsmokers. It is argued that the inverse association among current smokers seen in some studies might result from residual confounding by smoking. 49 In the third EPIC study, among current smokers inverse effects were seen for fruit and vegetable consumption combined and separately and lung cancer risk, which is in line with the previous study of Linseisen et al within the EPIC cohort and with the pooled analyses of cohort studies published by Smith-Warner et al. 55 and 57 Additionally, Büchner et al were able to classify risks by smoking status. In current smokers, statistically (borderline) significant inverse associations emerged between the consumption of fruit and vegetables combined and separately and of citrus fruits and risk of squamous cell carcinomas, the type of lung cancer most strongly related to smoking. 56

A recent systematic review from Japanese epidemiologic studies showed that fruit consumption possibly decreases the risk of lung cancer but found an insufficient relationship between vegetable consumption and risk of lung cancer. 58

A prospective cohort study by Yun et al showed that the combination of both behaviors (vegetable preference and LPA) was more protective against lung cancer among current smokers than among former or never-smokers in multivariate analysis. 59 In this study population, only government employees and teachers were included, and all women were excluded, which might have limitations for generalization.

Red and processed meat intake has been hypothesized to play a role in carcinogenesis. The fat content of red meat, the carcinogenic products resulting during high-temperature cooking and preservation, and the endogenous formation of mutagens from heme present in meat are implicated in the pathway of carcinogenesis.62, 63, 64, 65, 66, 67, and 68

Tasevska et al's cohort study observed a moderate positive association between meat consumption and lung carcinoma. A high intake of red and processed meat increased the risk of lung carcinoma in men; in women, the risk with high red meat intake was less pronounced, and no risk was observed with processed meat intake. 69 In a case-control study involving 1216 women using a dietary questionnaire similar to that used by Tasevska et al, Sinha et al found a borderline statistically significant increase in the risk of lung cancer for well-done, fried, and broiled red meat intake.65 and 70

Cross et al found an elevated risk of lung cancer for the highest compared with the lowest quintile of red meat (1.20; 95% CI, 1.10-1.31) and processed meat (1.16; 95% CI, 1.06-1.26) intake. 71

Many case-control and cohort studies reported inconsistent findings for meat intake.65, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, 87, and 88

Discussion

This systematic review shows an inverse association between lung cancer and LPA. More physically active individuals have a reduced risk of lung cancer. The reduction affects men and women alike, is greater for high LPA (ie, frequent, vigorous, or heavy exercise) than for moderate LPA (ie, moderate or medium levels) and displays a significant dose-response relationship. Most of the studies that have attempted to find an association between OPA and lung cancer have failed. Table 1 is a summary of the most important studies investigating the relationship between LPA and lung cancer.

Table 1 Study Summary of Leisure Time Physical Activity and Lung Cancer

Reference, Location Design, N Type of Measurement Exposure Level and RR (95% CI) Adjustment Effect on Lung Cancer Incidence
Severson et al 13

Honolulu Heart Study
Cohort; 8066 men, 194 cases Interview questionnaire 65-68/86

Usual time per 24 h

Basal, sleeping/lying down (34.4%)

Sedentary, sitting/standing (39.06%)

Moderate (gardening/carpentry)/heavy (shoveling/digging) (26.56%)
Reference low first, second = 1.06 (0.76-1.48)

Third = 0.70 (0.48-1.01)

P = .039
Age, BMI, smoking Decreased
Albanes et al 26 NHANES a Cohort; 5138 men, 114 cases Interview questionnaire 71-75/82-84

Frequent exercise (23.2%) reference

Moderate exercise (39.4%)

Little or no exercise (37.4%)
Frequent exercise

RR = 1.00

Moderate exercise

RR = 1.0 (0.6-1.6)

Little or no exercise

RR = 0.9 (0.6-1.5)

P = .80
Age, BMI, smoking, race, energy intake No significant difference
Thune and Lund 21

Norway Health Survey Cardiovascular Diseases
Cohort; 81,516 men, 413 cases; women, 51 cases Mailing validated questionnaires 72-78 past year LPA

R1: reading, watching TV other sedentary

R2: walking, bicycling/physical activities 4 h/wk (male, 19.84%; female, 22.14%)

R3: exercise to keep fit, 4 h/wk (male, 54.61%; female, 66.73%)

R4: regular hard training or participation in competitive sports several times a week (male, 25.22%; female, 9.85%)
Men: Reference low 1.00

Moderate 0.75 (0.60-0.94)

Regular training R3 + R4

0.71 (0.52-0.97) P = .01 lowast

Women: Reference low 1.00

Moderate 0.91 (0.48-1.71)

Regular training R3 + R4

0.99 (0.35-2.78) P = .88
Age, BMI, smoking, geographic area Decreased in men

No significant difference in women
Lee et al 15

US Harvard Alumni
Cohort; 13,905 men, 245 cases Mailing validated questionnaires 1977-1993

past year LPA

Levels for kJ/wk:

< 4200 (32.2% men) (n = 4476)

4200-8399 (28.4% men) (n = 3946)

8400-12,599 (18.1%) (n = 2513)

≥ 12,600 kJ/wk (21.4%) (n = 2970)
Reference low

4200-8399; RR = 0.87 (0.64-1.18)

8400-12,599;

RR = 0.76 (0.52-1.11)

≥ 12,600; RR = 0.61 (0.41-0.89)

P trend = 0.008 lowast
Age, BMI, smoking, current walking, stair climbing Decreased
Wannamethee et al 22

UK BRHS b
Cohort; 7735

men, 265 cases
Nurse-administered validated questionnaire 78/80/97

Usual life pattern of LPA

Inactive/moderate: cycling recreational activities, regular walking/sport once a week (78.57%)

Moderate/vigorous: sporting activity once a week/frequent cycling, frequent activity/walking/frequent sport (14.67%)

Vigorous: very frequent sporting/plus other (6.76%)
Reference low

RR = 1.00

Moderately vigorous

RR = 0.77 (0.49-1.21)

Vigorous

RR = 0.76 (0.40-1.43)

P = .19
Age, BMI, smoking, alcohol, social class Decreased
Colbert et al 27

Finland ATBC c Study
Cohort; 27,082 men, 1441 cases Nurse-administered questionnaire 85/88/93

past year LPA

Sedentary: reading, watching television (41.52%)

Moderate: walking, hunting, gardening fairly regularly

Heavy: running, skiing, swimming fairly regularly (58.48%)
Reference low:

RR = 1.00

Moderate + heavy: active

RR = 0.97 (0.87-1.07)
Age, BMI, smoking, education, supplement energy intake, vegetable intake No significant difference
Kubík et al 10

Czechoslovakia
Hospital-based case-control; 269 female cases, 1079 controls In-person interviews past 10 y LPA

Physical exercise (hours/week)

0 h (43.9%)

1-5 h: (26%)

> 5 h: (30%)
Reference low level: R = 1.00

Moderate: 0.62 (0.42-0.92)

High active: 0.42 (0.29-0.62)

P < .001 lowast
Age, smoking, education, residence Decreased
Mao et al 11

Canada
Population-based case-control; 1131 men cases, 997 female cases, 3106 controls Mailing questionnaire 94/97 past year LPA

Physical activity (specific metabolic equivalent MET) moderate MET ≥ 3 to ≤ 6: (%)

Vigorous MET > 6: (%)

Total (moderate plus vigorous): (%)
Reference low level: OR = 1.00

Men

Moderate: 0.91 (0.71-1.17)

High active: 0.79 (0.61-1. 04)

Women

Moderate: 0.73 (0.55-0.98)

High active: 0.69 (0.51-0.93)
Age, BMI, alcohol, smoking, ETS, occupation, education, residence, energy intake, vegetable intake Decreased
Sinner et al 19 (IWHS) d Cohort; 36,410 women, 777 cases Women questionnaire 87/89/92/97

Moderate physical activity: bowling, golf, light sports or physical exercise, gardening, taking long walks

Vigorous physical activity: jogging, racquet sports, swimming, aerobics, strenuous sports

High physical activity level score: vigorous activity 2 or more times a week or moderate activity more than 4 times per week

Moderate physical activity level score: vigorous activity once a week or moderate activity 1-4 times a week
Reference low: R = 1.00

Moderate: 0.84 (0.71-1.00)

High: 0.77 (0.64-0.94)
BMI, smoking status, pack-years of smoking, education, marital status, alcohol intake, coffee intake, and vegetable intake Deceased

lowast P trend significant.

a National Health and Nutrition Examination Survey.

b British Regional Heart Study.

c Alpha-Tocopherol Beta-Carotene Cancer Prevention Study.

d Iowa Women's Health Study.

Abbreviations: BMI = body mass index; CI = confidence interval; ETS = exposure tobacco smoke; IWHS = Iowa Women's Health Study; LPA = leisure-time physical activity; MET = 1 MET is the average seated resting energy cost for an adult and is set at 3.5 mL/kg per min of oxygen; RR = relative risk.

To determine the relationship between physical activity and lung cancer, it is necessary to obtain valid and reproducible measurements. This can be difficult because physical activity is a very complex behavior that can be conducted and measured in many ways. Questionnaires and interviews used in surveys remain the most frequently used methods for assessment of LPA in epidemiologic studies.89 and 90 A related limitation of some studies is that physical activity was measured only once, and it is important that further prospective studies assess physical activity at several time points throughout the follow-up period using a more comprehensive, objectively verifiable measure of physical activity.

All studies adjusted for important confounding factors such as age. One study adjusted for occupational exposure. 11 Some studies also adjusted for race, education level, energy intake, BMI, vegetable intake, residential exposure, alcohol, and social class ( Table 1 ).

Almost all studies selected adjusted for smoking in terms of the amount of tobacco use (pack-years or number of daily cigarettes and numbers of years smoked), and 4 studies stratified current smokers by the number of cigarettes smoked.11, 12, 21, and 27

The majority of studies that researched the influence of diet on lung cancer risk found an inverse association between lung cancer risk and consumption of fruits and vegetables. Table 2 is a summary of the most important studies that investigated the influence of nutrition on the incidence of lung cancer.

Table 2 Study Summary of Nutrition and Lung Cancer Incidence

Study Name Subjects, Country Nutritional Intervention Effect on Lung Cancer Incidence Adjustment
CARET a Chemoprevention Trial (1989-2001) 52 United States: 14,120 participants, 742 lung cancer cases Fruits, vegetables, β-carotene supplements Decrease

Decrease (P = .003)

Statistically significant increase
Age, smoking, asbestos exposure, sex, race, BMI, education
Cohort Study (1993-2001) 49 Denmark: 54,158 participants, 247 lung cancer cases Plant foods Decrease Age, smoking
ATBC b Cancer Prevention Study (1985-1993) 51 Finland: 27,084 male smokers, 1644 lung cancer cases Fruits (rich in β-carotene, α-carotene, lycopene, and β-cryptoxanthin)

Vegetables (rich in β-carotene, α-carotene, lycopene, and β-cryptoxanthin)
Decrease Age, education, smoking, area of residence, marital status, BMI
Prospective Study (1984-1996) 53 United States: 77,283 Women, 519 lung cancer cases

Men: 47,778, 274 lung cancer cases
Fruits

Vegetables

Fruits

Vegetables
Decrease

No statistically significant association
Age, smoking

BMI, physical activity, alcohol intake
EPIC c Study (1992-1999) 54 Europe (10 European countries): 478,021 participants, 860 lung cancer cases Fruits

Vegetables
Decrease

No statistically significant association
Age, smoking

BMI, sex
EPIC c Study(1992-2000) 57 Europe: 478,590 participants,1126 lung cancer cases Fruits

Vegetables
Decrease

Decrease only in current smokers
Age, smoking,

BMI, sex, education, alcohol intake, histologic type of tumor
EPIC c Study (1991-2000) 56 Europe: 521,468 participants, 1830 lung cancer cases Fruits

Vegetables and fruits combined
Decrease

Decrease
Age, smoking

BMI, sex, education, occupation, physical activity, alcohol intake, histologic type of tumor

a CARET = β-Carotene and Retinol Efficacy Trial.

b ATBC = Alpha-Tocopherol, Beta-Carotene Cancer Study.

c EPIC = European Prospective Investigation into Cancer and Nutrition.

Some studies examined lung cancer according to Kreyberg cell type. Other analyses stratified by age and alcohol intake. Because of the powerful influence of smoking on lung cancer incidence and the correlations between many smoking characteristics and diet, smoking is a strong confounder in associations between fruit and vegetable consumption and lung cancer risk and therefore was assessed rigorously in many studies.

Conclusion

Summarizing these results, we conclude that physical activity and specifically LPA (moderate and high) can reduce the incidence of lung cancer. The studies reporting the opposite studied a small number of patients, involved only OPA, or were not adjusted for smoking. Most of the studies showed higher inverse associations between lung cancer and physical activity in smokers than in nonsmokers. Concerning the association between fruit and vegetable consumption and the incidence of lung cancer, most of the studies proved an inverse association, although some studies showed a clear protective effect of fruits only. It is not clear if this inverse association is more intense between smokers or nonsmokers and which histologic types of lung cancer it affects more.

A well-planned trial should focus on both physical activity and attitudes about diet. It should contain a large number of participants who undergo face-to-face interviews and should be adjusted for many parameters such as smoking, age, sex, histologic type of lung cancer, education, and BMI.

Smoking remains the predominant risk factor for lung cancer, and public health efforts should continue to focus on smoking prevention and cessation as a means of reducing the incidence and mortality of this lethal disease. Besides smoking, it is also important to focus on the chemoprevention of lung cancer. Chemoprevention is the use of specific natural or synthetic substances with the objective of reversing, suppressing, or preventing carcinogenic progression to invasive cancer. Phase III chemoprevention clinical trials for lung cancer have been carried out, studying > 70,000 patients for more than a decade, with mostly negative results.91, 92, 93, 94, 95, 96, 97, 98, 99, and 100 Most of the experience with potential chemopreventive agents such as retinoids and antioxidants in individuals at risk for lung cancer have been negative so far. Moreover, β-carotene was associated with an increased lung cancer incidence in 2 large randomized studies, most likely because of negative interaction with cigarette smoke.51 and 52 This underlines the necessity of finding new concepts for chemoprevention trials in a more cost-effective and time-efficient manner.

Many clinical trials are ongoing and focus on chemoprevention of lung cancer. The use of molecularly targeted therapeutic and biological agents in association with nutrition and physical activity habits could constitute novel strategies for lung cancer prevention.

Disclosure

The authors have stated that they have no conflicts of interest.

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Footnotes

1 Amalia Fleming General Hospital, Athens, Greece

2 Oncology Unit GPP, Sotiria General Hospital, Athens School of Medicine, Athens, Greece

3 Division of Hematology/Oncology, Tufts Medical Center, Tufts University, School of Medicine, Boston, MA

lowast Address for correspondence: Kostas N. Syrigos, MD, PhD, Oncology Unit GPP, Sotiria General Hospital, Athens Medical School, GR, 152 Mesogeion, Athens and 115 27, GR; Visiting Professor of Thoracic Oncology, Yale School of Medicine, New Haven, CT


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