Lung Cancer Energetics

J.W. Rohen and Yokochi, C., 1983. Color Atlas of Anatomy. Igaku-Shoin, New York, N.Y. pgs. 247

Lungs Anatomy

Lung Cancer

It snuffs life!

It kills!

It cripples!

It suffocates!

It devastates!

And so it does. Lung cancer is the most common form of cancer in humans. Yet the public perspective differs to a degree:

Normal Microscopic Lung Tissue

Things we think we Know:

a.  Only 1 out of 5 (21.6%) people acknowledge the fact that lung cancer is the leading cause of cancer deaths in the US.

b.  8 out of 10 (80%) of all lung cancers are related to smoking.

c. 25 of 100 (25.4%) people realize that lung cancer kills more men then prostate cancer.

d. 17 of 100 (17.8%) women understand that more women die from lung cancer then from breast cancer.

e. 18 out of 100 (16-20%) of smokers develop lung cancer from smoking however the risk from smoking is projected on to other ailments that include, heart disease, stroke, emphysema and peripheral vascular disease, which are also slow killers.

Another truism that seems at odds with public awareness is that a fair number of smokers usually quit smoking spontaneously without knowing that they have developed the malignancy. Unfortunately lung cancer also occurs in non-smokers especially those exposed to Radon gas emanating from the ground only 12% of people are aware of that.

Lung Cancer Research and Funding:

From the research perspective lung cancer receives the lowest dollar amounts in grants, contracts and funding: Lung cancer ($ in millions) $188 versus Breast cancer at $765, Prostate cancer at $329 and colon cancer at $297. This disparity follows from the stigmata that rule the public and political forums that lung cancer is induced by smoking and therefore the patients, so afflicted, brought it upon themselves. 

Age adjusted incidence of Lung Cancer

The hue and cry over Breast Cancer surpasses Lung Cancer funding nationwide in the US and has a significant impact. Although more women are diagnosed with breast cancer then lung cancer, a larger percentage of women die with lung cancer then breast cancer (as mentioned below is due to early diagnosis and funding). In the case of men this is the largest “cancer-killer” of all. Since there are a larger proportion of patients alive with breast cancer, they are able to motivate a stronger advocacy group.

World wide Distribution of Cancer

Worldwide Incidence of Lung Cancer:

Worldwide 1.6 million people are diagnosed with Lung cancer and 1.4 million die from it. The high death rate is predictably due to the fact the since the lungs are air-filled cavity the tumor mass does not displace enough normal function until it is too late. Persistent cough, shortness of breath and chest pains are fairly late stage occurrences, except when the location of the tumor dictates these symptoms early. When the location is near the lobar bronchus (cough and shortness of breath) or a peripheral tumor located next to the pleura (lining of the lung that carries nerves) causing pain, the patient is more likely to seek help.

Early Detection and Screening:

Early diagnosis remains elusive although a recent study by the National Cancer Institute called the NLST (National Lung Screening Trial) involved 53,000 high-risk individuals (deemed high risk from current and former smoking history). The screening was based on Chest X-Rays or Low Dose Spiral CT scans done annually for five years. The data clearly showed a bias towards the Spiral CT scanning technique’s superiority by 20%. The dilemma remains about the inherent slightly increased risk of radiation exposure from the Spiral CT scanning technique and its potential DNA mutational possibility. Besides affordability of the technique (X-Rays cost $40 vs., Spiral CT scan $400) and accessibility the radiation risk for early detection remains a troubling fact. IN other words detecting the disease early is the goal however given repeated CT scans raises the risk of radiation induced lung cancer. Comparatively X-Rays yield 15 times less Radiation then the CT scan. Emerging technologies will solve this dilemma in the very near future.

VisionGate Technology

The sputum cytology is also being used for early detection based on the epigenetic damage of the DNA within the cell. The cells are subjected to DNA analysis and known mutations or high irregularity of the DNA itself raise the suspicion index for further study. Another technology under way is the Cell-CT, which is a non-invasive procedure that determines the probability of cancer on the basis of the sputum cell morphological characteristics via multi-view (500 different angled 2-dimension views) scanned visualization of the individual cell as it passes through light-microscopy and is represented in a 3-D image. The accuracy is unsurpassed based on initial data and a company called VisionGate is in the process of obtaining FDA approval for creating a diagnostic machine for use in large-scale laboratories.

Types of Lung Cancer:

Alveolar Cell

Squamous Cell

Lung Cancer is divided into two main groups: 80% NSCLC (Non small cell lung cancer) and 20% SCLC 

Adenocarcinoma

(Small cell lung cancer). Although the former (NSCLC) has four distinct pathological presentations, (Adeno-carcinoma, Squamous cell carcinoma, Large Cell carcinoma and Alveolar Cell Carcinoma) they have been lumped under the same category due to near identical responses to past chemotherapy and radiation therapy treatments. However with new understanding of the biology of each cell type the distinctions are becoming obvious. These distinctions will help stratify and tailor therapy for the individual patients, rather than lumping them into one category and using the same shot-gun approach. The process of defining the differences is underway.

SCLC (Oat Cell)

Risk Factors:

a.  Smoking accounts for 80% of the lung cancer in males and 50% in females. Interestingly the incidence is highest in North America, Northern Europe, New Zealand and Australia where there is the lowest prevalence of adult smokers at 4%. While in Italy with 20% adult smokers the incidence rates are lower. Chinese women have 21.3 cases per 100,000 and Germany has a16.4 while Italy is at 11.4. This disparity may indicate a genetic weakness to cancer and the environmental risks. Male lung cancer incidence and death rates however are declining in the Western Countries due to cessation of smoking. The female incidence has stabilized after rising in the past decade. This is due to women having taken up smoking later. However the intensity of smoking is declining in both genders in the younger populations. It is no longer hip to smoke.

b.  Radon (Rn86) is a radioactive gas that emanates as a natural decay byproduct of Uranium. It is found naturally in the earth soil. It has a short half-life of 3.8 days but has intense radioactivity. It is odorless and colorless. It collects in the attics and the basements and in natural spring water. Radon is implicated in 21,000 lung cancer cases per year in the United States.

Worldwide distribution of Radon Intensity

c.  Indoor air pollution from unventilated coal-burning stoves – exposure to Polycyclic Aromatic Hydrocarbons.

Asbestos

Asbestos Fibers

Fibers in the Lung

Mesothelioma

d.  Asbestos is a naturally occurring silicate used for fire and heat resistance. It was used extensively in buildings, especially ceilings and roof tiles, in naval shipyards and talc powder. Asbestos comes in 6 different forms but all are considered carcinogens in humans. Long-term exposure causes a disease called Mesothelioma and due to the chronicity of the persistence of the insoluble fibers it is implicated in lung cancer. Patients with Mesothelioma have a higher incidence of lung cancer.

e.  Arsenic is found in the earth. It occurs naturally in the underground water. There is an epidemiological link between lung cancer and the exposure to the arsenic. The risk increases even more when tobacco smoking.

Arsenic

f.  Polycyclic Aromatic Hydrocarbons (PAH) are known risks for lung cancer. PAH are involved in aluminum production, coal gasification, coke production, iron and steel foundries, tar distillation, shale oil extraction, wood impregnation, roofing, road paving, carbon black production, carbon electrode production, chimney sweeping, and calcium carbide production. In addition, workers exposed to diesel engine exhaust in the transport industry.

Genetics:

Family history of lung cancer usually suggests that there may be a genetic defect especially if no external agencies as identified above have been established. Family history of a younger individual getting diagnosed is of concern and family members of individuals with lung cancer should be alert to the familial possibility in spite of the smoking history that may have been a contributory causative agent in that person. This may suggest a weak genetic basis for the external influence of smoking.

Noguchi M. Stepwise progression of pulmonary adenocarcinoma–clinical and molecular implications. Cancer Metastasis Rev. 2010;29:15-21.

Springer Science 1 Business Media

Similar to other cancers like for example Colon cancer, there is linear, cumulative and progressive mutational events on the DNA. The most frequent genetic aberrations are the p53, KRAS, FHIT, EGFR, CDKN2, RB and Myc genes. Additionally deletions in chromosomes 1 (1p36), 3 (del 3p), 9 (del 9p) are also seen not uncommonly.

Epigenetic modulation via DNA mehylation or Hypermethylation has been seen in protein p16 (TP16), CDH13 (Cadherin 13), APC and RASSFIA genes.

Recently younger non-smoker patients have been found with NSCLC with inversion in Chromosome 2 with fusion of EML4 gene and the ALK gene. This and several other gene/protein targets are being investigated in therapeutic trials against the cancer. (To be discussed in a later entry)

Prevention:

1. Stop Smoking.
2. Stop Coal burning in unventilated environments.
3. Check basement and attics for Radon. (Vacuuming the dust and submitting it under a Geiger counter will help determine).
4. Eat vegetables and fruits
5. If you have been a smoker go for annual examination and consider sputum cytology evaluation for DNA mutation if available. Otherwise consider the low dose spiral CT scan as a base-line after discussing with your physician.
6. If you have been exposed to Asbestos in your life obtain a Chest X-Ray as a baseline, after discussing with your physician..
7. Discuss all aspects of your past history, symptoms with your physician and the need for any evaluation.

Reference:

1. STATEMENT CONCERNING THE NATIONAL LUNG SCREENING TRIAL

       October 28, 2010 http://www.cancer.gov/images/DSMB-NLST.pdf

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