Doctor’s blog

Studies of molecular genetics have shown that lung cancer cells acquire many properties before turning to malignant form. These include activation of dominant oncogenes (which try to tilt the balance toward cancer formation) and inactivation of tumor-suppressor or recessive oncogenes (which try to suppress cancer) in genetic lesions. Lung cancer cells accumulate in these genetic lesions which may be more than 20 in number. A small portion of cells (less than 1%) in a tumor are responsible for the full malignant behavior and these cells are called cancer stem cells. A large bulk of the cells in cancer is formed from these cancer stem cells. They are clonally related to the cancer stem cell but themselves cannot regenerate the full malignant phenotype for metastatic disease and unlimited replicative potential. These cancer stem cells are very important in the treatment because unless they are identified and removed cancer can not be treated successfully. These cancer stem cells are more resistant to chemotherapy than the bulk.    

Changes in dominant oncogenes include point mutations in the coding regions of oncogenes, mutations in the tyrosine kinase domain and amplification, rearrangement, and/or loss of transcriptional control of oncogenes.

A large number of tumor suppressor genes (recessive oncogenes) at the time of pathogenesis of lung cancer. This inactivation is also result of mutation. Due to the mutation the tumor suppressor genes are left with functionally inactive alleles which lead to loss of function of tumor suppressor genes and single dominance of dominant oncogenes.

Lung cancer, like many other epithelial cancers, arises by a multi step process that involves both carcinogens causing mutation known as “initiation” and tumor promoters. Preventive measures of lung cancer as well as other cancer can be directed towards these factors to be successful.

Genetic Predisposition: Though lung cancer is not a familial disease there are certain factors which indicates some relation of lung cancer with familial predisposition. For example patients living till adulthood with retinoblastoma (tumor of eye) and Li-Fraumeni syndrome can develop lung cancer more commonly than can be explained by simple coincidence. Another factor is the first degree relative of lung cancer patients have 2 to 3 fold increase incidence of lung cancer than general population, many of which are not related to smoking.

The most important cause of lung cancer is cigarette smoking. Most of the lung cancers are caused by carcinogens and tumor promoters inhaled via cigarette smoking. The relative risk of developing lung cancer is increased about thirteen fold (1300%) by active smoking and about 1.5-fold by long-term passive exposure to cigarette smoke than non smokers.

The lung cancer death rate is related to the total amount of cigarettes smoked expressed in “cigarette packs per year” such that the risk is increased 60 to 70 fold for a man smoking two packs a day for 20 years as compared with a nonsmoker. The chance of developing lung cancer decreases with cessation of smoking, but it may never return to the nonsmoker level.

Women have a higher relative risk per given exposure than men (approximately1.5-fold higher), this means if a man and a woman smokes two packs of cigarettes a day the woman has 1.5 times more chance of developing lung cancer than man. This difference may be due to a greater susceptibility to tobacco carcinogens in women, but there is controversy.

Chronic obstructive pulmonary disease (COPD), a lung disease which is also smoking-related, also increases the risk of developing lung cancer.

About 15% of lung cancers occur in individuals who have never smoked (pure non smoker) and the majority of these are found in women. The reason for this sex difference may be due to hormonal factors, but it is not clear.

Radiation is an environmental cause of lung cancer. People exposed to high levels of radon or receiving thoracic radiation therapy have a higher than normal incidence of lung cancer, particularly if they smoke.

Prevention: Prevention is by efforts to get people to stop smoking. smoking cessation is extremely difficult, because the smoking habit represents a powerful addiction to nicotine along with it psychological addiction. In one study in Australia it was fond to be more difficult to stop smoking than stop alcohol. It is because smoking becomes a habit, a part of personality.

Counseling, behavioral therapy, nicotine replacement (gum, patch, sublingual spray, inhaler), and antidepressants (such as bupropion) are available to motivate smokers to give up the habit. But the methods are successful in only 20–25% of individuals. So the best is to prevent people from starting to smoke. In the United States prevalence of smoking is 28% for males and 25% for females, age 18 years or older and 38% of high school seniors smoke.

Lung cancer is the commonest type of cancer in terms of incidences (cases) and also in terms of death. It causes more deaths in females than breast cancer. In USA in 2007 lung cancer affected more than 114,760 males and about 98,620 females. 86% die within 5 years of diagnosis of lung cancer and makes it the leading cause of cancer death in both men and women. In 2007 in USA number of death from lung cancer were approximately 89,510 for men and approximately 70,880 in women, whereas breast cancer deaths in women were 40,460 in 2007 in USA in 2007.

Globally at present lung cancer incidence is more than 1.2 million (1,200,000) in men and about 400,000 cases in women. Number of deaths due to lung cancer globally at present is about 900,000 for men and 300,000 for women, a total of approximately 1.2 million. The total number of death due to lung cancer is going to be about 10 million by the year 2030, according to The International Agency for Research on Cancer. This roughly calculates to one lung cancer case for every 3 million cigarettes smoked.

The incidence of lung cancer is highest between ages 55 and 65 years. Lung cancer is responsible for more deaths in the United States every year than breast cancer, prostate cancer and colon cancer, combined. The incidence and age-adjusted death rate in males is decreasing, but in females it is stable or still increasing. These death rates are related to smoking; smoking cessation efforts begun 40 years ago in most developed countries in men and are responsible for the decrease in incidence and death rates in men. But women started smoking in large numbers about 10–15 years later than men and smoking cessation efforts are not particularly aimed at women. This is the main reason of increase of lung cancer incidences in women. Smoking cessation efforts need to increase for women. 

In the past 30 years, 5-year overall lung cancer survival rate has nearly doubled to about 15%. The improvement is due to advances in combined-modality of treatment with surgery, radiotherapy, and chemotherapy.