Lung cancer is the leading cause of cancer death worldwide. Smoking is the primary risk factor, responsible for about 80% of lung cancer cases. Other risk factors include exposure to radon, asbestos, and other environmental carcinogens. Genetic factors also influence lung cancer risk. Lung cancer incidence varies globally and is highest in North America, Europe, and East Asia. In Bangladesh, lung cancer is the most common cancer in men and the 4th most common in women. Histologically, lung cancers are classified as small cell carcinomas, non-small cell carcinomas such as adenocarcinomas and squamous cell carcinomas, and other less common subtypes. Molecular analysis has revealed frequent mutations in genes
Lung cancer; epidemiology,etiology and classification
1. An Overview of
Epidemiology, Etiology and
Classification of Lung
Cancer
Presented by
Dr.Shah Ashiqur Rahman Ashiq
Choudhury
Phase-A Resident,
Pulmonology,BSMMU
2. Background
Lung cancer was once a very rare disease, so rare that
doctors took special notice when confronted with a case,
thinking it a once-in-a-lifetime oddity.
Cigarettes were recognized as the cause of the
epidemic in the 1940s and 1950s, with the confluence of
studies from epidemiology, animal experiments, cellular
pathology and chemical analytics.
As late as 1960 only one-third of all US doctors believed
that the link of lung cancer with cigarettes had been
established.
3. Sir Richard DollSir Richard Doll
• 1950 study linking1950 study linking
smoking to lung cancersmoking to lung cancer
• 1954: Doll and Hill1954: Doll and Hill
published “The Mortalitypublished “The Mortality
of Doctors and Theirof Doctors and Their
Smoking Habits” in BMJSmoking Habits” in BMJ
(lead to most M.D. giving(lead to most M.D. giving
up smoking)up smoking)
8. Lung cancer is the most common visceral malignancy,
accounting for roughly one-third of all cancer deaths.
It is the most common cause of cancer-related death in
both men and women.
More than 225,000 individuals was diagnosed with lung
cancer and over 150,000 individuals died from the
disease in the United States in 2013.
The incidence of lung cancer peaked among men in the
late 1980s and has plateaued in women.
9.
10. In the 40 countries comprising Europe, lung cancer
accounts for 12 % of approximately 3.2 million new
cancer cases and 19.9 % ( 342,000) of cancer related
deaths.
Lung cancer is rapidly emerging as a major cause of
mortality in the Middle East, Africa, and Asia as well.
Approximately 70,000 annual cancer-related deaths are
currently attributed to lung cancer in Japan. More than
130,000 lung cancer deaths occur annually in China.
11. • The incidence of lung cancer varies considerably among
different ethnic populations throughout the world.
• Among men, African Americans had the highest
incidence of lung cancer risk ( approximately 7.5 % ) ,
where as Swedes had the lowest cumulative risk
(approximately 2 % ) .
• Among women, cumulative lung cancer risk was highest
in African Americans (approximately 3 .5 % ) , whereas
French and Korean women had very low cumulative
risks (approximately 1% ) .
13. Bangladesh is still lacking a national cancer registry.
Cancer is the sixth leading cause of death in Bangladesh
(BBS, 2008).
According to the cancer registry report of National
Institute of Cancer Research Hospital (NICRH) with the
collaboration of WHO and Bangladesh Government,
Lung cancer is the most common cause of cancer in
male and 4th
common cause of cancer in female.
A recent WHO study has been estimated that there are
196,000 lung cancer cases in Bangladesh among those
aged 30 years or above.
17. Smoking
About 80% of lung cancer occur in smokers or those
who stopped recently.
The risk becomes 60 times greater among habitual
heavy smokers compared with non smokers.
Although cessation of smoking decreases the lung
cancer risk over time but it may never return to the
baseline levels.
Passive smoking increases the risk of lung cancer
development approximately twice than that of non-
smokers.
18.
19. Not all person exposed to tobacco smoke develop lung
cancer and this is because the mutagenic effect of
carcinogens in smoke is modified by genetic variants.
Specific and highly polymorphic p-450 monooxygenase
enzyme has an increased capacity to activate the
procarcinogens in smoke.
Similarly, smokers whose peripheral blood lymphocyte
show more numerous chromosomal breakage after
exposure to tobacco related carcinogens have 10 fold
higher risk of developing lung cancer than others.
21. Second hand smoke or environmental tobacco
smoke contains numerous human carcinogens
for which there is no safety level.
It is estimated that about 3000 non-smoking
adults die of lung cancer as a result of breathing
second hand smoke
Cigars and pipe smoking also increase the risk
but much less than smoking cigarettes.
23. Arsenic (naturally)
inorganicorganic (carcinogen)
Insecticides, weed killers, rat poison, Fungicides,
wood preservatives, Paints, leather industry.
Chromium
• Natural element, odourless and tasteless.
• Chromium (VI) or hexavalent chromium is
carcinogenic.
• Chrome plating, Stainless steel welding
24. Nickel
Polycyclic Aromatic Hydrocarbons (PAHs)
Agroup of over 100 different chemicals that
are formed during the incomplete burning of coal,
oil, gas, garbage.
Diesel fuel exhaust is a prevalent source of PAHs.
Some PAHs are used to make medicines, dyes, plastics, and pesticides.
26. Lung cancer itself is a risk factor for a 2nd
lung cancer.
Other Lung diseases like scars( due to
TB, fibrosis; specially idiopathic pulmonary
fibrosis) and Chronic Obstructive
Pulmonary Disease can increase the risk
of lung cancer
27. Genetic Predisposition
“Driver” mutation plays a key role in neoplastic
transformation of pulmonary epithelial cells.
Some of these genetic changes associated with cancer
can be found in the “benign” bronchial epithelium of
smokers without lung cancers.
This suggests that large areas of respiratory mucosa are
mutagenized by exposure to the carcinogens of tobacco.
This phenomenon is called “field effect”
28. Genetic Predisposition
• Oncogenes:
• activation of oncogenes or
inactivation of tumor suppressor
genes.
–Proto-oncogenes are believed to turn
into oncogenes when exposed to
particular carcinogens.
–Mutations in the K-ras proto-oncogene
are responsible for 10–30% of lung
adenocarcinoma.
29. • Chromosomal damage:
– Chromosomal damage can lead to loss of
heterozygosity
– This can cause inactivation of tumor
suppressor genes.
– Damage to chromosomes 3p, 5q, 13q, and
17p are particularly common in small-cell lung
carcinoma.
– The p53 tumor suppressor gene, located on
chromosome 17p, is affected in 60-75% of
cases.
30. • Epidermal Growth Factor Receptor (EGFR)
– EGFR regulates cell
proliferation, apoptosis, angiogenesis, and
tumor invasion
– Mutations and amplification of EGFR can
lead to cancerous growth, esp. non-small-
cell lung cancer (basis for the treatment
with EGFR-Inhibitors)
31. • Genetic polymorphisms
– People with genetic polymorphisms are more
likely to develop lung cancer after exposure
to carcinogens.
– These include polymorphisms in genes coding
for
» interleukin-1,
» cytochrome P450,
» apoptosis promoters such as caspase-8,and
» DNA repair molecules such as XRCC1
35. Squamous Cell Carcinoma
Highly associated with smoking and harbors diverse
genetic aberrations including chromosomal deletions
involving the tumour suppressor loci.
Chromosomal deletions in 3p,9p(site of CDKN2A gene)
and 17p( site of the TP53 gene) are the early events in
tumour evolution.
Squamous cell carcinoma shows highest frequency of
TP53 mutations of all histologic types of lung carcinoma.
36. Squamous Cell Carcinoma (contd.)
Loss of expression of Retinoblastoma(RB) tumour
suppressor gene is identified by immunohistochemistry
in 15% of squamous cell carcinoma.
The CDKN2A is inactivated and its protein product p16,is
lost in 65% of tumours.
It has been recently recognized that many squamous cell
carcinomas have amplifications of FGFR1, a gene
encoding the fibroblast growth factor receptor tyrosine
kinase.
38. Small Cell Carcinoma
Small cell carcinoma has the strongest association with
smoking and despite its diverse histological features
shares many molecular features with squamous cell
carcinoma.
Most common genetic aberrations include loss of
function of TP53( 75%-90% of tumours), RB( close to
100% of the tumours) and chromosome 3p deletions.
Also common in amplification of MYC gene family.
40. Adenocarcinoma
Adenocarcinoma is marked by oncogenic gain-of-
function mutations involving the components of growth
factor rececptor signalling pathways.
These include gain-of-function mutations in multiple
genes encoding receptor tyrosine kinase such as:
EGFR,ALK,ROS,MET and RET which are all also
mutated in the other forms of cancer.
Tumours without tyrosine kinase gene mutations often
have mutations in the KRAS gene.
41.
42. Lung Cancers in Never Smokers
The WHO estimates that 25% of lung cancer worldwide
occurs in never smokers.
This cancer commonly occurs in women and mostly are
adenocarcinomas.
Cancers in non-smokers are more likely to have EGFR
mutations and almost never have KRAS mutations.
TP53 mutations are not uncommon but occur less
frequently than in smoking related cases.
44. Classification of Malignant Lung
Tumours
Importance of Classification:
Consistency in patient treatment
Provision of basis for epidemiologic and biological
studies.
On the basis of origin, lung carcinoma can be divided into:
A. Primary Lung Tumour: Arises from lung itself
B. Secondary Lung Tumour: Arises from elsewhere.
45. Histologic Classification of Lung
Carcinoma in Resected Specimens
1) Pre-invasive leisons
a) squamous dysplasia b) atypical adenomatous
hyperplasia c) adenocarcinoma in situ d)
diffuse idiopathic pulmonary neuro-endocrine
cell hyperplasia
2) Squamous cell carcinoma
a) Papillary b) small cell c) clear cell d) basaloid
3) Small cell carcinoma
Combined small cell carcinoma
46. 4) Adenocarcinoma
a) minimally invasive b) invasive adenocarcinoma
5) Large cell carcinoma
a) large cell neuro-endocrine carcinoma b)
basaloid
c) lympho-epithelioma like carcinoma d) clear cell
e) large cell carcinoma with rhabdoid prototype
6) Adenosquamous carcinoma
47. 7) Sarcomatoid Carcinomas
a) Pleomorphic b) spindle cell c) giant cell
d) carcinosarcoma e) plumonary
blastoma
8) Carcinoid Tumours
9)Carcinoma of Salivary gland types
a) Mucoepidermoid b) adenoid cystic c)
epimyothelial carcinoma
48. The relative proportions of major
histopathological categories
0%
5%
10%
15%
20%
25%
30%
35%
40%
1st
Qtr
Adenocarcino
ma
Squamous cell
carcinoma
Small cell
carcinoma
Large cell
carcinoma
Others