Lung cancer: What are the links with oxidative stress, physical activity and nutrition

doi:10.1016/j.lungcan.2013.09.009

Lung Cancer

Volume 82, Issue 3, December 2013, Pages 383-389

https://doi.org/10.1016/j.lungcan.2013.09.009 Get rights and content

Abstract

Oxidative stress appears to play an essential role as a secondary messenger in the normal regulation of a variety of physiological processes, such as apoptosis, survival, and proliferative signaling pathways. Oxidative stress also plays important roles in the pathogenesis of many diseases, including aging, degenerative disease, and cancer. Among cancers, lung cancer is the leading cause of cancer in the Western world. Lung cancer is the commonest fatal cancer whose risk is dependent on the number of cigarettes smoked per day as well as the number of years smoking, some components of cigarette smoke inducing oxidative stress by transmitting or generating oxidative stress. It can be subdivided into two broad categories, small cell lung cancer and non-small-cell lung cancer, the latter is the most common type. Distinct measures of primary and secondary prevention have been investigated to reduce the risk of morbidity and mortality caused by lung cancer. Among them, it seems that physical activity and nutrition have some beneficial effects. However, physical activity can have different influences on carcinogenesis, depending on energy supply, strength and frequency of exercise loads as well as the degree of exercise-mediated oxidative stress. Micronutrient supplementation seems to have a positive impact in lung surgery, particularly as an antioxidant, even if the role of micronutrients in lung cancer remains controversial. The purpose of this review is to examine lung cancer in relation to oxidative stress, physical activity, and nutrition.

Introduction

Oxidative stress plays important roles in the pathogenesis of many diseases, including aging, degenerative disease, and cancer [1], and it has been shown that oxidative mechanisms have a role in the initiation, promotion and progression of carcinogenesis [2]. Lung cancer is the commonest fatal cancer whose risk is dependent on the number of cigarettes smoked per day as well as the number of years smoking, some components of cigarette smoke inducing oxidative stress by transmitting or generating Reactive Oxygen Species (ROS) [3]. Human lung cancer can be subdivided into two broad categories, small cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), the latter is the most common type. Efficacy of exercise-training as an adjunct therapy for patients diagnosed with NSCLC both before and following pulmonary resection has been reported [4], [5]. However, physical activity can have different influences on carcinogenesis, depending on energy supply, strength and frequency of exercise loads as well as the degree of exercise-mediated oxidative stress [6].

Nutrition has also been thought to account for about 30% of cancers in Western countries, making diet second to tobacco as a preventable cause of cancer [7]. In fact, impaired nutrition and weight loss are important predictors of perioperative complications in lung cancer patients. On the other hand, micronutrient supplementation seems to have a positive impact in lung surgery [8], particularly as an antioxidant, even if the role of micronutrients in lung cancer remains controversial [9]. The purpose of this review is to examine lung cancer in relation to oxidative stress, physical activity, and diet.

Section snippets

Reactive oxygen species and NO: what are their roles?

Free radicals are reactive compounds that have one or more unpaired electrons in their valence shell [10]. Their lifetime is very short ranging from milliseconds to nanoseconds. They can mediate cell damage by extracting electrons from a stable molecule in an attempt to pair up their own electrons, thus leaving the original molecule in an unstable state. They are produced at low levels during normal physiological conditions and are scavenged by endogenous antioxidant systems. ROS represent the

ROS and lung cancer

A primary consequence of oxidative stress is lipid peroxidation, the end products of lipid peroxidation can lead to subsequent pathological consequences, particularly in lung, through the rearrangement of the lipoperoxyl radical (ROO) [16]. Oxidative DNA damage by reactive oxygen species is also thought to contribute to carcinogenesis. In fact, it has been shown that ROS-induced DNA damage involves single- or double-stranded DNA breaks, purine, pyrimidine, or deoxyribose modifications, and DNA

ROS and physical activity

To date, approximately 80 studies have been conducted investigating the effects of structured exercise training in patients following a diagnosis of cancer. Results showed that structured exercise training is a safe and well-tolerated therapeutic strategy associated with significant improvements in a broad range of cancer-related toxicities including fatigue, exercise capacity, and physical quality of life [23]. Physical activity (PA) is also associated with numerous health benefits, especially

Primary prevention

Distinct measures of primary prevention have been investigated to reduce the risk reductions of morbidity and mortality caused by lung cancer. In fact, physical activity might influence the risks for cancers at several sites, and the evidence is most consistent for colon cancer, pancreatic cancer, endometrial cancer and prostate cancer [27]. However, little is known about whether physical activity is associated with similar risk reductions in lung cancer [4], [6]. Moreover, the efficacy of

Nutrition and lung cancer

Besides the specific role of PA in primary and secondary prevention of lung cancer, many studies have focused on the effect of nutrition in modifying the risk of this pathology. It appears that a high consumption of fruits and vegetables can be an important element of primary prevention [46]. In fact, through the several potentially beneficial antioxidants, fibers, minerals, and phytochemicals fruits and vegetables contain, they may help prevent cancer and contribute to maintenance of a healthy

Perspectives

Oxidative mechanisms play a role in the initiation, promotion and progression of carcinogenesis. The past decade has witnessed an increase in clinical and research interest in the role of exercise on the incidence of lung cancer and following a cancer diagnosis. It appears that physical activity is a safe and feasible supportive intervention to improve symptom control and cardio-respiratory fitness in cancer patients with early-stage disease either during or following the completion of adjuvant

Conflict of interest statement

The authors have no conflicts of interest to declare.

Acknowledgement

The authors thank Mrs Martine Collomb for her writing assistance.

References (56)

C.L. Granger et al.
Exercise intervention to improve exercise capacity and health related quality of life for patients with non-small cell lung cancer: a systematic review
Lung Cancer
(2011)
L.W. Jones et al.
Effects of aerobic training on oxidative status in postsurgical non-small cell lung cancer patients: a pilot study
Lung Cancer
(2011)
V. Afonso et al.
Reactive oxygen species and superoxide dismutases: role in joint diseases
J Bone Spine
(2007)
T.B. Kryston et al.
Role of oxidative stress and DNA damage in human carcinogenesis
Mutat Res
(2011)
J.S. Penta et al.
Mitochondrial DNA in human malignancy
Mutat Res
(2001)
D.G. Yanbaeva et al.
Systemic effects of smoking
Chest
(2007)
D. Planchard et al.
The NER proteins are differentially expressed in ever smokers and in never smokers with lung adenocarcinoma
Ann Oncol
(2009)
T. Thirumalai et al.
Intense and exhaustive exercise induce oxidative stress in skeletal muscle
Asian Pac J Trop Dis
(2011)
A. Koutsokera et al.
Nutrition habits, physical activity, and lung cancer: an authoritative review
Clin Lung Cancer
(2013)
M. Filaire et al.
Evolution of the early respiratory function after lung resection for cancer
Rev Pneumol Clin
(2009)

K. Nezu et al.

Recovery and limitation of exercise capacity after lung resection for lung cancer

Chest

(1998)

F. Leo et al.

Respiratory function changes after chemotherapy: an additional risk for postoperative respiratory complications?

Ann Thorac Surg

(2004)

S. Margaritora et al.

Is pulmonary function damaged by neoadjuvant lung cancer therapy? A comprehensive serial time-trend analysis of pulmonary function after induction radiochemotherapy plus surgery

J Thorac Cardiovasc Surg

(2010)

A.M. Allen et al.

Do dose-volume metrics predict pulmonary function changes in lung irradiation?

Int J Radiat Oncol Biol Phys

(2003)

R. Gopal et al.

Effects of radiotherapy and chemotherapy on lung function in patients with non-small-cell lung cancer

Int J Radiat Oncol Biol Phys

(2003)

C.J. Peddle-McIntyre et al.

Feasability and preliminary efficacy of progressive resistance exercise training in lung cancer survivors

Lung Cancer

(2012)

J. Garcia-Tirado et al.

Effects of flavonoids in the prevention of lung cancer: systematic review

Med Clin

(2012)

H. Skuladottir et al.

Does insufficient adjustment for smoking explain the preventive effects of fruit and vegetables on lung cancer?

Lung Cancer

(2004)

N. Tasevska et al.

A prospective study of meat, cooking methods, meat mutagens, heme iron, and lung cancer risks

Am J Clin Nutr

(2009)

K.L. Uy et al.

Improved results of induction chemoradiation before surgical intervention for selected patients with stage IIIA-N2 non-small cell lung cancer

J Thorac Cardiovasc Surg

(2007)

L. Behrend et al.

Reactive oxygen species in oncogenic transformation

Biochem Soc Trans

(2003)

F. Masri

Role of nitric oxide and its metabolites as potential markers in lung cancer

Ann Thorac Med

(2010)

N. Okumura et al.

Against lung cancer cells: to be or not to be: that is the problem

Lung Cancer Int

(2012)

H.K. Na et al.

Effects of physical activity on cancer prevention

Ann N Y Acad Sci

(2011)

T.J. Key et al.

Diet, nutrition and the prevention of cancer

Public Health Nutr

(2004)

V. Matzi et al.

The impact of preoperative micronutrient supplementation in lung surgery. A prospective randomized trial of oral supplementation of combined α-ketoglutaric acid and 5-hydroxymethylfurfural

Eur J Cardiothorac Surg

(2007)

H.T. Yang et al.

Riboflavin at high doses enhances lung cancer cell proliferation, invasion, and migration

J Food Sci

(2013)

B. Halliwell et al.

Free radicals in biology and medicine

(2007)

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ReviewLung cancer: What are the links with oxidative stress, physical activity and nutrition

Abstract

Introduction

Section snippets

Reactive oxygen species and NO: what are their roles?

ROS and lung cancer

ROS and physical activity

Primary prevention

Nutrition and lung cancer

Perspectives

Conflict of interest statement

Acknowledgement

Lung Cancer

Lung Cancer

J Bone Spine

Mutat Res

Mutat Res

Chest

Ann Oncol

Asian Pac J Trop Dis

Clin Lung Cancer

Rev Pneumol Clin

Chest

Ann Thorac Surg

J Thorac Cardiovasc Surg

Int J Radiat Oncol Biol Phys

Int J Radiat Oncol Biol Phys

Lung Cancer

Med Clin

Lung Cancer

Am J Clin Nutr

J Thorac Cardiovasc Surg

Reactive oxygen species in oncogenic transformation

Biochem Soc Trans

Role of nitric oxide and its metabolites as potential markers in lung cancer

Ann Thorac Med

Against lung cancer cells: to be or not to be: that is the problem

Lung Cancer Int

Effects of physical activity on cancer prevention

Ann N Y Acad Sci

Diet, nutrition and the prevention of cancer

Public Health Nutr

The impact of preoperative micronutrient supplementation in lung surgery. A prospective randomized trial of oral supplementation of combined α-ketoglutaric acid and 5-hydroxymethylfurfural

Eur J Cardiothorac Surg

Riboflavin at high doses enhances lung cancer cell proliferation, invasion, and migration

J Food Sci

Free radicals in biology and medicine

Review
Lung cancer: What are the links with oxidative stress, physical activity and nutrition