Lifestyle Interventions in the Prevention and Treatment of Cancer

Clarence H. Brown III, MD; Said M. Baidas, MD; Julio J. Hajdenberg, MD; Omar R. Kayaleh, MD; Gregory K. Pennock, MD; Nikita C. Shah, MD; Jennifer E. Tseng, MD


Am J Lifestyle Med. 2009;3(5):337-348. 

In This Article

Lung Cancer

Lung cancer is the leading cause of cancer-related death in the United States, comprising 31% of cancer deaths in men and 25% of cancer deaths in women. An estimated 215 020 new cases of lung cancer will have been diagnosed in this country in 2008, and 161 840 deaths will have been attributed to lung cancer in 2008.[1] Approximately 85% to 90% of lung cancers are related to tobacco use.[1] Furthermore, approximately half of all patients with lung cancer have quit smoking before their diagnosis.

Worldwide, nearly a billion men are cigarette smokers, including approximately 35% of men in developed countries and 50% of men in developing countries. Worldwide, approximately 250 million women are smokers, including 22% of women in developed countries and 9% of women in developing countries. Currently, in the United States, approximately 25% of the adult population is smokers, or approximately 46 million adults.

There has been significant interest in evaluating the risk of lung cancer in both smokers and nonsmokers. Approximately 1 in 10 lifelong smokers will develop lung cancer. The risk of lung cancer increases with duration of smoking and with the number of cigarettes smoked daily.[1] Approximately 1.6% of lung cancer cases are attributable to secondhand smoke. Authors have found a relative risk of 1.14 to 5.20 in persons who never smoked but who resided with a smoker.[2,3] Furthermore, exposure to secondhand smoke in childhood has been found to carry a relative risk of lung cancer in adulthood of 2.6.[4]

A role for genetic susceptibility for the development of lung cancer includes data that show that only approximately 10% of smokers will develop lung cancer. In addition, studies demonstrate clustering of lung cancer within certain families. Li and Hemminki[5] reported a germline epidermal growth factor T790M sequence variation in a family with multiple cases of lung cancer. Bailey-Wilson et al[6] reported the results of a genome-wide linkage study of 52 families, which demonstrated a new major susceptibility locus influencing lung cancer risk at 6q23-25p. Hung et al[7] reported a locus at chromosome 15q25 associated with lung cancer. In this analysis of 3502 lung cancer case patients and 7377 controls, the risk of lung cancer was 30% higher for people with one copy of the marker at chromosome 15q25 and 70% to 80% higher for persons with 2 copies of the marker. The region where the marker resides contains 3 genes that encode subunits of the nicotine acetylcholine receptor.

The field of molecular epidemiology focuses on evaluation of susceptibility to environmental carcinogens. Within this field, a number of investigators have evaluated the role of genetic variability in susceptibility to the carcinogenic effects of nicotine. One such gene is the CYP2D6, a gene in the cytochrome P450 family that plays an important role in the metabolism of many common drugs and activates tobacco smoke-derived nitro-samine. Studies by Spitz and colleagues[8] show that 90% of the US population are extensive metabolizers, increasing their risk for lung cancer. This is related to the enzyme's high risk of activating tobacco carcinogens. The remaining 10% of the population are poor metabolizers, with a lower associated decreased risk of lung cancer due to a lower ability to activate tobacco carcinogens.

Another gene that may affect genetic susceptibility to lung cancer is the glutathione GSTM1 gene.[8] This gene belongs to a large family of genes that facilitate the detoxification of a variety of carcinogens, including polycyclic aromatic hydrocarbons present in tobacco smoke. Individuals who have the GSTM1 enzyme are able to detoxify carcinogens using this metabolic pathway, whereas those individuals lacking this enzyme are less able to detoxify carcinogens and therefore have a higher lung cancer risk.

Diets that are rich in fruits and vegetables have been suggested to have a protective effect against the development of lung cancer, possibly due to their rich antioxidant content.[9,10] Researchers have hypothesized that micronutrients protect against oxidative damage to DNA, thereby conferring a protective effect against cancer.[11] Early studies by Bjelke[12] suggested a protective effect of vitamin A against lung cancer. However, randomized studies evaluating the effects of beta-carotene and retinoids (vitamin A derivatives) have not demonstrated protective effects against lung cancer.[13,14,15]

At least 21 studies have demonstrated a protective effect of exercise against lung cancer risk. A Norwegian study[16] demonstrated a 25% to 29% reduction in the risk of lung cancer in men who engaged in moderate exercise (at least 4 hours per week) compared to sedentary men; this effect was demonstrated after controlling for tobacco use. Another study[17] reported results from the Harvard Alumni Health Study, which followed 13 905 men for up to 16 years. After accounting for tobacco use, men who engaged in light, moderate, and strenuous amounts of exercise on a regular basis were shown to have, respectively, a 13%, 24%, and 39% reduction in lung cancer risk.[17] It should be noted that many of these studies are cohort studies conducted in white populations of higher socioeconomic status.

Smoking prevention and cessation are critical in the prevention of lung cancer and in improving outcomes of lung cancer patients. Evidence from the Copenhagen Health Study demonstrated that smoking cessation reduces the risk of development of lung cancer by 50%. Primary prevention of tobacco use has also been demonstrated to be a successful strategy in reducing lung cancer incidence rates in states such as California, which have strong antitobacco legislation.

Data also demonstrate that smoking cessation is associated with improved survival after a diagnosis of lung cancer and in improved treatment efficacy.[18,19] Gritz et al[20] reported that in a population of 840 patients with a diagnosis of stage I non-small cell lung cancer, 40% who were smokers at the time of diagnosis subsequently quit smoking.

Ongoing tobacco use can adversely affect outcomes of surgery, radiation, and chemotherapy.[18,19] The incidence of postoperative complications is increased in smokers; this rate is decreased in patients who have quit smoking prior to surgery.[18] Continued smoking may also decrease the efficacy of chemotherapy for lung cancer. There is evidence that nicotine increases the metabolism of multiple drugs via the induction of hepatic enzymes, which may decrease the efficacy of certain chemotherapy agents.[21] Smoking cessation at the time of diagnosis furthermore decreases the rate of subsequent lung cancers.[22,23]


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