Lung Cancer Overview
Epidemiology of Lung Cancer
is the primary cause of cancer mortality in the United States and other
countries.1,2 Since 1985, lung cancer has been the most common
cancer worldwide in terms of incidence and mortality.1 In 2012,
there were approximately 1.82 million new cases and 1.59 million deaths of lung
cancer worldwide.3,4 Therefore, the current burden of lung cancer is
possibly underestimated.1 Although in 1980 69% of lung cancer cases
were in developed countries, currently approximately 50% of cases occur in
developing countries.1 According to Cheng and colleagues, lung
cancer incidence was highest in very high HDI (Human Development Index)
countries and lowest in low HDI countries.4 Furthermore, in most
countries with high HDI, as male incidence continued to decrease, female
incidence gradually increased.4 Since 1985, the global estimated
number of lung cancer cases in men and women has increased by 51%.3 Relative
survival rate ranges from 2% (Lybia) to 15.6% (United States) to 30% (Japan).4
Approximately 85% of the lung cancer cases are comprised of Non-small cell lung
cancer (NSCLC).5 Today, immunotherapeutic strategies such as
adoptive T-cell transfer, vaccines, and checkpoint inhibitors are undergoing
developments for the treatment of NSCLC.5 These latest techniques
are providing scientists with optimism for vastly improving lung cancer
of Lung Cancer The
relationship between tobacco smoking and lung cancer incidence has been proven
in many ecological and clinical studies.3 Decline in lung cancer
death rates in women started more than a decade after declining in men.1
This lag is related to the fact that that cigarette smoking in women peaked two
decades later than in men.1 Today, lung cancer incidence and
mortality rate data indicate a promising change from the steep rise in the
1970s and appear to be reaching a plateau.4 Generally, the incidence and mortality
rates are equal because most patients diagnosed with lung cancer die of it.1,4
1964, the U.S. Public Health Service published a report in which they explained
the negative effects of smoking on health, particularly, its progression of
lung cancer.6 Since the publication of this report, yearly
consumption of cigarettes has declined in the United States.6 Moreover,
prevalence of smoking is higher in adults below the federal poverty level and individuals
with less than a high school diploma.6 Also, prevalence of smoking
is higher in the South and Midwest regions of the United States.6 There
are more than 4000 chemical constituents of cigarette smoke, and the
International Agency for Research on Cancer (IARC) has identified at least 50
carcinogens in tobacco smoke.7,8 The agents of concern in lung
cancer are the tobacco-specific N-nitrosamines
(TSNA), which are produced during tobacco processing and smoking.7,8
These carcinogens covalently bind to the DNA and form DNA adducts. If repair
processes fail to remove these DNA adducts or the cells fail to undergo
apoptosis, permanent mutations occur. Ultimately, these mutations lead to
uncontrolled cell division and tumor development.9 The lung cancer risk is proportional
to the quantity of cigarette consumption or degree of exposure to the
carcinogens.10 Other factors, such as individual susceptibility,
also play a role in development of lung carcinoma.1,2 Even though
more than 80% of lung cancers occur in people who had exposure to tobacco smoke
throughout their lives, less than 20% of smokers (1 in 9) develop lung cancer.10
Hence, it is important to consider environmental factors and genetic
predispositions when explaining variabilities in lung cancer susceptibility.1,10 Other
forms of smoking have been proven to contribute to lung cancer development.7
Regular cigar and pipe smokers are at greater risk of developing lung cancer given
that they are exposed to a larger quantity of carcinogens during their lifetimes.1
Furthermore, histologic modifications similar to the premalignant stage
have been observed in the bronchial epithelium of regular marijuana and cocaine
has been reported that secondhand smoke contributes to approximately 17% of
lung cancer in non-smokers who were exposed to high levels of environmental
tobacco smoke (ETS) in their childhood and adolescence.2,12
Furthermore, wood smoke exposure and air pollution in industrialized nations have
been attributed to lung cancer risk factor. Occupational carcinogens including
asbestos, radon gas, and diesel fumes among others have also been reported to
have a role in lung cancer development.2,13 Approximately 15% of lung cancers in
men and 53% in women are not attributed to smoking.14 This accounts
for 25% of lung cancers worldwide.14 Moreover, the incidence of lung
cancer in never-smokers appears to have a geographic variation across the globe.1
Never-smoker women are more frequently affected than men. Furthermore, smokers
mainly develop SCLC and squamous cell carcinoma, but non-smokers are mostly
associated with adenocarcinoma.15 Hereditary
components could also contribute to the lung cancer risk factors list.15,16
Smoking history is associated with a 3-fold increase in the risk for people
with family history of lung cancer.16 A candidate susceptibility
genes study has shown that there are genes of low penetrance and high frequency
that are associated with absorption, metabolism, and accumulation of tobacco and
other carcinogens in the lung tissue.1 Host genetic factors
determine lung cancer susceptibility. Therefore, persons with genetic
predispositions are at higher risk of developing lung cancer.16
Like many other cancers, lung cancer is also related to diet and obesity. It
has been reported that low serum concentration of antioxidants could take part
in development of lung cancer.17 On the other hand, there have been
studies highlighting that lung cancer patients receiving Beta-Carotene
supplementation have a higher than expected mortality.18,19 These
studies, however unsettling, should serve to remind people that lack or
excessive intake of vitamins can potentially be harmful.1 Consumption
of raw fruit and vegetables has been reported to be associated with a decrease
in the risk of lung cancer development. 20 In a study by Wu and colleagues,
airway obstruction has been associated with lung cancer development.21
Additionally, certain infectious agents including human papillomavirus (HPV),
Epstein-Barr virus, Chlamydia pneumonia, and pulmonary tuberculosis have been reported to be involved in
the development of lung cancer.1 A greater possibility of
coinfection with oncogenic viruses has increased the risk of lung cancer in HIV-positive
individuals.22 Basic Biology and Treatment Options Lung
cancer appears in the cells of the lung and bronchus epithelium, which can be
divided to small cell lung cancer and non-small cell lung cancer.1 Adenocarcinoma
is the most common type of lung cancer. The mechanism of damage of lung cancer
is very complex.5 Multiple levels of molecular alteration including
genetics, epigenetics, and protein expression should be evaluated when it comes
to prognostication, diagnosis, and
treatment of lung cancer.23 Identification of mutations such as ALK
and EGFR have enabled scientist to develop targeted therapy for lung
adenocarcinoma.23 Targeted therapy approach minimizes drug toxicity.5
Nevertheless, only 20% of lung cancer cases have identifiable targets.5,24
Therefore, cytotoxic chemotherapy is the only treatment option for the
remaining 80%.5,24 Today, enhancements in understanding the
mechanisms of immune system in response to cancer have led to development of
immunotherapeutic methods for treatment of NSCLC.5 Active
immunotherapeutic approach targets regulation of the host’s immune system. In
contrast, passive immunotherapeutic approach does not use the host’s immune
machinery.5 Monoclonal antibodies and adoptive T-cell transfer are
examples of passive immunotherapy strategies. Disease
Prevention and Proposed Solutions The first and most
recommended approach to lung cancer prevention is abstaining from smoking and
exposure to secondhand smoke. This is especially important for individuals who
have a family history of lung cancer. The U.S. Preventive Service Task Force
(USPSTF) and Center for Medicine and Medicaid Services have suggested annual
lung cancer screenings for patients above 55 years who are or used to be heavy
smokers.25 Furthermore, regardless of screening results, physicians and
other healthcare professionals are urged to encourage patients to quit smoking during
every visit.25 Smokers coming in for screening should be provided
with evidence-based, behavioral, and pharmacologic treatment options to aid
them in smoking cessation. 25 However, more research is needed to
determine the potential adverse effects of screening on smoking behavior.6,25
It is important to keep in mind that most of the patients that come in for
screening are lifetime smokers that started to smoke in their adolescence or
early adulthood. Therefore, a more comprehensive approach, such as educating
the youth regarding the potential harms of smoking, could also help many people
from being at a higher risk for developing lung cancer in the first place.
1. Dela Cruz CS, Tanoue LT, Matthay RA. Lung Cancer:
Epidemiology, Etiology, and Prevention. Clinics in chest medicine. 2011;32(4):10.1016/j.ccm.2011.09.001.
2. Torre L.A., Siegel R.L., Jemal A. (2016) Lung Cancer
Statistics. In: Ahmad A., Gadgeel S. (eds) Lung Cancer and Personalized
Medicine. Advances in Experimental Medicine and Biology, vol 893. Springer,
Cham. doi 10.1007/978-3-319-24932-2
3. Didkowska J, Wojciechowska U, Ma?czuk M, ?obaszewski J.
Lung cancer epidemiology: contemporary and future challenges worldwide. Annals
of Translational Medicine. 2016;4(8):150. doi:10.21037/atm.2016.03.11.
4. Cheng T-YD, Cramb SM, Baade PD, Youlden DR, Nwogu C, Reid
ME. The International Epidemiology of Lung Cancer: Latest Trends, Disparities,
and Tumor Characteristics. Journal of thoracic oncology?:
official publication of the International Association for the Study of Lung
Cancer. 2016;11(10):1653-1671. doi:10.1016/j.jtho.2016.05.021.
N. The state of the art in non-small cell lung cancer immunotherapy. Semin
Thorac Cardiovasc Surg. 2014;26:26–35.
6. Dube S, Asman K, Malarcher A, et al. Cigarette smoking
among adults and trends in smoking cessation—United States 2008. Office on
Smoking and Health, National Center for Chronic Disease Prevention and Health
Promotion, CDC. 2009
7. Smith CJ, Perfetti TA, Rumple MA, et al. “IARC group 2A
Carcinogens” reported in cigarette mainstream smoke. Food Chem Toxicol. 2000;
8. Smith CJ, Perfetti TA, Mullens MA, et al. “IARC group 2B
Carcinogens” reported in cigarette mainstream smoke. Food Chem Toxicol. 2000; 38(9):825–848.
A, Ward E, Hao Y, et al. Trends in the leading causes of death in the United
States, 1970– 2002. JAMA. 2005; 294(10):1255–1259.
P, Bray F, Parkin DM. Estimates of the world-wide prevalence of cancer for 25
sites in the adult population. Int J Cancer. 2002; 97(1):72–81.
NJ, Watt HC. Prospective study of effect of switching from cigarettes to pipes
or cigars on mortality from three smoking related diseases. BMJ: British Medical Journal.
Fligiel SE, Roth MD, Kleerup EC, et al.
Tracheobronchial histopathology in habitual smokers of cocaine, marijuana,
and/or tobacco. Chest. 1997; 112(2):319–326. PubMed: 9266864
SH, Roth MD, Kleerup EC, et al. Histopathologic and molecular alterations in
bronchial epithelium in habitual smokers of marijuana, cocaine, and/or tobacco.
J Natl Cancer Inst. 1998; 90(16):1198–1205. PubMed: 9719080
DM, Bray F, Ferlay J, et al. Global cancer statistics, 2002. CA Cancer J Clin.
2005; 55(2): 74–108. PubMed: 15761078
A, Hirai T, Ohtake Y, et al. Lung cancer associated with Werner’s syndrome: a
case report and review of the literature. Jpn J Clin Oncol. 1997; 27(6):415–418.
MR, Hong WK, Amos CI, et al. A risk model for prediction of lung cancer. J Natl
Cancer Inst. 2007; 99(9):715–726.
K, Tangrea JA, Barrett MJ, et al. Serum alpha-tocopherol and subsequent risk of
lung cancer among male smokers. J Natl Cancer Inst. 1999; 91(20):1738–1743.
Omenn GS, Goodman GE, Thornquist MD, et al.
Effects of a combination of beta carotene and vitamin A on lung cancer and
cardiovascular disease. N Engl J Med. 1996; 334(18):1150–1155.
GS, Goodman GE, Thornquist MD. Risk factors for lung cancer and for
intervention effects in CARET, the Beta-Carotene and Retinol Efficacy Trial. J
Natl Cancer Inst. 1996; 88(21):1550–1559.
DA, Eldridge AL, Peters JC. Dietary carotenoids and lung cancer: a review of
recent research. Nutr Rev. 1999; 57(5 Pt 1):133–145.
AH, Fontham ET, Reynolds P, et al. Previous lung disease and risk of lung
cancer among lifetime nonsmoking women in the United States. Am J Epidemiol.
RT. Non-AIDS-defining malignancies in HIV. Top HIV Med. 2008; 16(4):117–121.
Cooper WA, Lam DCL, O’Toole
SA, Minna JD. Molecular biology of lung cancer. Journal of Thoracic Disease. 2013;5(Suppl 5):S479-S490. doi:10.3978/j.issn. 2072-1439.2013.08.03.
Morgensztern D, Campo MJ,
Dahlberg SE, et al. MOLECULARLY TARGETED THERAPIES IN NON-SMALL CELL LUNG
CANCER ANNUAL UPDATE 2014. Journal of thoracic oncology?: official publication of the International Association for the Study of
Lung Cancer. 2015;10(1 0 1):S1-63.
Fucito LM, Czabafy S,
Hendricks PS, Kotsen C, Richardson D, Toll BA. Pairing Smoking-Cessation
Services With Lung Cancer Screening: A Clinical Guideline From the Association
for the Treatment of Tobacco Use and Dependence and the Society for Research on
Nicotine and Tobacco. Cancer. 2016;122(8):1150-1159.