Associations with tobacco and cancer

1. TOBACCO & CANCER
-Dr. Sanketh Kotne M.D., D.M.
Consultant Medical Oncologist

2. TOPICS COVERED
● HISTORY OF TOBACCO
● PREVALENCE IN INDIA
● EPIDEMIOLOGY
● CANCER RISK WITH SMOKING
● EVOLUTION OF TOBACCO PRODUCTS AND VARIOUS TYPES
● CARCINOGENS IN THE TOBACCO AND ITS SMOKE
● BIOMARKERS
● HOW IT LEADS TO CANCER
● HOW IT AFFECTS ANY ONGOING TREATMENT
● NICOTINE REPLACEMENT THERAPY
● ANTI-TOBACCO CAMPAIGNS

3. HISTORY
● First discovered by the native people of Mesoamerica and South America and later
introduced to Europe and the rest of the world.
○ Used in spiritual ceremonies
○ Used in ethnobotany for medical treatment of physical conditions
○ As a pain killer- earache and toothache

4. ● Introduced to India in the 17th century by the portuguese merchants.
● It later merged with existing practices of cannabis smoking which has been there
since 2000 B.C.

5. ● Data from GATS (Global Adult Tobacco Survey)
● Largest global public health survey system
● Household surveys (14 countries→ 36 countries)
● 1.3 billion tobacco users → 6 million annual deaths due to tobacco use

6. PREVALENCE IN INDIA

9. ● From the introduction of mass-manufactured, mass-marketed cigarette, smoking
rates grew
● Peaked in 1960-70s

10. Tobacco Control Policy Interventions:
● Implementation of Graphic health warnings in Canada 1999-
reduction upto 4.5% points over a decade.
● Tobacco control activities are estimated to have averted 8 million
premature deaths and extended mean life span by 19-20yrs
● WHO + FCTC(Framework Convention on Tobacco Control) –
measures to control labeling and marketing of tobacco products.

11. EPIDEMIOLOGY
● 1800s – excessive cigar use -oral cancers
● 1930s – Germans- Link b/n smoking and Lung cancer
● Acc to U.S Surgeon General by cancer site, the Yearly smoking attributable
mortality was linked with Lung.
● Likelihood of dying from lung cancer with smoking increased from
− 2.73 → 12.65-→ 25.66 RR Women
− 12.22 → 23.81 → 24.97 RR Men

12. Tobacco use behaviours depends on
● No. of cigarettes smoked
● Patterns of smoking on individual cigs
● No. of Years smoked

13. CANCER RISK WITH SMOKING
Common index of cancer risk
● Pack-years – No. of Packs of cig smoked per day X No. of Years smoked lifetime

14. ● Primary driver: Nicotine
● Major addictive substance
● Smokers consume a relatively stable no. of cigs/day in a consistent manner to
maintain an acceptable level of nicotine in their system.
● Depends on the rate of Nicotine metabolism

15. ● Tar- main contributor to smoking caused disease.
● Tar- Collected particulate o of smoke, less water and nicotine(Nicotine
free-dry particulate)
● Studies: Painting mice with tar → cancerous tumors
● Reducing tar yields might reduce disease burden.

16. Evolution of Tobacco products
● Many countries reduce tar yield from 15mg-10mg- But no effective results
in disease burden.
● Increase in adenocarcinomas of lung- due to changes in cigs – Filters,
Filter ventilation and Tobacco-specific Nitrosamines
● Elastic cigs : Allows smokers to adjust their puffing patterns to regulate
intake of nicotine

17. VARIOUS FORMS OF MANUFACTURED TOBACCO

19. ● 2000s- Sweden- Manufactured smokeless products – Electronic cigarettes-
Vaporizes nicotine solution.
● Electronic Nicotine Delivery System-ENDS (Not FDA approved)

20. CARCINOGENS IN TOBACCO PRODUCTS AND PROCESSES OF CANCER
DEVELOPMENT
● Identified as carcinogenic -1950s
● IARC(International Agency for Research on Cancer)- Group I Carcinogens-
Smoke and Smokeless tobacco
● Identified 72 carcinogens in cigarette smoke

21. VERYIMPORTANT

22. LISTOFCARCINOGENSINTOBACCOANDTOBACCOSMOKE

24. ● N-nitrosamines
● Benzene, 1,3-butadiene,
● Aromatic amines
● Cadmium
● Polycyclic aromatic hydrocarbons (PAH) - found in coal tar, soot, broiled foods,
and automobile engine exhaust.
● Benzo(a)pyrene (BaP) has substantial carcinogenic activity.
● Carbonyl compounds: formaldehyde and acetaldehyde- found in copious
amounts in cigarette smoke- from the combustion of sugars and cellulose.
rank highly

25. ● Smoke contains a number of aromatic amines: bladder carcinogens 2-
aminonaphthalene and 4- aminobiphenyl, heterocyclic amines, and furans.
● Toxic metals: are also present in cigarette smoke in measurable quantities*
− Beryllium
− Cadmium (0.22–0.78 μg)
− Lead (0.97–2.64 μg)
− Polonium-210
*May depend on part of the world grown

26. N-nitrosamines: well-established carcinogens
● Two compounds in tobacco :
● 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), which is derived
from nitrosation of nicotine
● N′-nitrosonornicotine (NNN), which is derived from nitrosation of nornicotine
● Tobacco specific
● Form during the curing process for tobacco -(leaves are dried through contact
with combustion gases from heat (flue) curing or microbial activity in air curing.)
● NNK : Potent Lung carcinogen
Nasal cavity, pancreas, liver
● NNN: Respiratory tract, Esophagus
*It is possible to reduce nitrosamines by changing curing and storage practices

27. Smokeless products:
● Even smokeless products like e-cigs contain potent carcinogens- N-Nitrosamines
● Product type and composition has an enormous effect on nitrosamine levels.
● Smokeless products available in India are often far higher in nitrosamines.
● US smokeless products also can contain PAH and carbonyl compounds- from fire
curing the constituent tobacco.
● Also contain toxic metals

28. Strong evidence:
● PAH & N-Nitrosamines- Lung carcinogenesis; Also in Cervical cancers and respiratory
tract cancers
● Aromatic amines [4- aminobiphenyl and 2-naphthylamine] are potent bladder
carcinogens, and smokers - an elevated risk of bladder cancer.
● Benzene is a known cause of leukemia, it is presumed that this is the link to
leukemia observed in smokers.

29. BIOMARKERS
● Biomarkers of exposure - crucial for examining products for their potential to reduce
health risks associated with tobacco use.
● Validation of tobacco exposure biomarkers is threefold:
− Method validation
− validation with respect to product use
− validation with respect to disease risk
Validation with respect to product use: levels of a given biomarker differ substantially
between users and nonusers, and that biomarker levels decrease substantially when
product use is stopped.
Validation with respect to disease: variation in biomarker levels in product users are
predictive of variations in disease outcomes

31. How Tobacco use leads to cancer
Carcinogen exposure → Carcinogen- DNA adducts → Mutations → Cancer
[Hecht et al ]
● Cigarette smoking → Induce cytochrome P450 system → Metabolic
activation of carcinogens → Binds to DNA
(Higher levels of DNA adducts in cancer patients- Higher risk)
An individual’s balance of activation and deactivation of toxicants -important
predictor of cancer risk.

33. Treatment specific risks
Impact on chemo and Targeted therapy
● Effects Cytochrome P450 enzyme → altered drug clearance time and plasma
conc.
● Erlotinib, Bendamustine, Irinotecan
Impact on Radiation Therapy
● Treatment related complications
● Decrease treatment response

34. Impact on surgery:
● Increased rates of Post-op complications
● Decreased health QOL
● Delayed wound healing
● Increased infection rates, Cardiovascular events, Pulmoinary complications
● Mortality rates are higher in smokers

35. Nicotine replacement therapy (NRT)
● Medically-approved way to take nicotine by means other than tobacco.
● used to help with quitting smoking or stopping chewing tobacco.
● Increases the chance of quitting smoking by about 50- 70%
− adhesive patch
− chewing gum
− lozenges
− nose spray
− inhaler

36. ● Vary in the time it takes for the nicotine to enter the body and the total time nicotine
stays in the body.
● Patches are applied to the skin - stable dose of nicotine slowly over 16–24h
● Oral nicotine - quicker nicotine uptake into the body, but lasts a short time.
● Nicotine inhalers - metered-dose inhalers - administer nicotine through the
lungs and mucous membranes of the throat quickly, lasts a short time.

37. ● Blood nicotine levels
− Highest → 5–10 minutes after using the nicotine nasal spray
− 20 minutes after using a nicotine inhaler or chewing nicotine gum
− 2–4 hours after using a nicotine patch

38. Side effects of NRT
● Increase the risk of heart attacks
● Nicotine exposure during pregnancy - ADHD and learning disabilities in
the child.
● Transdermal patch is considered less safe for the fetus -it delivers
continuous nicotine exposure as opposed to the gum or lozenge, which
delivers intermittent and thus lower nicotine exposure

41. ANTI-TOBACCO CAMPAIGNS IN INDIA
● Quit Tobacco Movement (2008)
● Life Se Panga Mat Le Yaar (2011)
● Election Campaign (2014)
● Tambakhu Ko Dishum (2015)
● What Damage Will This Cigarette/ Bidi do (2018)

42. Anti-Tobacco Day: 31st MAY