tobacco and cancer ppt

1. DR.K.SENTHIL KUMAR

2.  LEADING CAUSE OF CANCER RELATED DEATH
WORLDWIDE.
 > 10 million of peoples die annually -due to tobacco related
illness.
 1.2 billion smokers and 100 millions of smokeless tobacco users.
 Global adult tobacco survey - 41% of men and 5% of women-
across the world currently smoke.
 Cigarettes are the main form of tobacco product consumed in the
world.
 Lung cancer is the most common malignancy caused by smoking.

3. Tobacco chewing in its various forms is directly responsible for
cancers of the oral cavity, esophagus and pancreas.
⦁ Tobacco smoking cause oral, pharyngeal, esophageal,
laryngeal, lung, stomach, kidney, urinary bladder, cervix, colon,
rectum and AML.

4. ⦁ Risk of TB is increased by 2-3 times in smokers as compared
to non smokers.
⦁ Males who smoke have a lower sperm count and poorer
sperm quality.
⦁ Decrease BMD thus increase risk of bone fractures.
⦁ Type 2 DM tends to progress more rapidly and have high
risk of insulin resistance in smokers.
⦁ High risk of Thrombo-embolic phenomenon – more stroke &
PE.

7.  Bidis
 Cigarettes
 Cigars
 Cheroots
 Chuttas
 Pipe
 Chillum
 Hookah
 Gutkha
 Khaini
 Mainpuri tobacco
 Mawa
 Mishri
 Paan
 Snuff
 Zarda

8.  Bidis (flavoured or unflavoured) - thin hand rolled
cigarettes tobacco wrapped in a tendu or temburni
leaf (plants native to Asia).
 Cigaretes- combination of cured and finely cut
tobacco, reconstituted tobacco and other
additives rolled or stuffed into a paperwrapped
cylinder.
 cigars- air-cured or dried tobacco. fermented in a
multi-step process that can take from 3 to 5
months -causes chemical and bacterial reactions
gives cigars a different taste and smell from
cigarettes.

9.  Cheroots
⦁ Filterless cylindrical cigar with both the ends open.
⦁ Roll of tobacco leafs with no wraps.
⦁ Less expensive then cigarette.
 Chutta
⦁ Cheroots with ignited end is placed inside mouth.
⦁ Mostly used inAndra Pradesh.
⦁ Increase risk of palate cancer.
 Dhumti
⦁ Kind of conical cigar made up of rolled tobacco leaf .
⦁ Ignited end is placed inside mouth.
⦁ Made by the smokers themself.

10. o Gutka-
⦁ Crushed arecanut along with sun dried tobacco.
⦁ Leads to Oral sub-mucous fibrosis (SMF).
⦁ Have addictive as well as carcinogenic effect
o Khaini-
⦁ Paste of tobacco + slaked lime + arecanut.
⦁ Slaked lime is added to make the mixture alkaline for better
absorption via mucosa.
⦁ Kept in bucco-alveolar region or vestibule.
 Mainpuri tobacco-
 Tobacco+ Slaked lime + finely cut arecanut + Camphor +
Cloves+Cinnamon.
 Mainly used in Uttar Pradesh.
 High incidence of oral cancer & leukoplakia.

11.  Mawa -
 Gujrati preparation of tobacco made up of thin shavings of
arecanut, tobacco and slaked lime.
 Requires vigorous mixing before consumption.
 Sold by vendors in cellophane papers tied like a small ball.
 Mishri-
 Prepared by roasting tobacco on a hot metal plate till it converted
into black powder and mixed with catechu.
 Used by applying powder over gums and teeth.
 Common used by females.
 More common in Maharastra.
 Pan (Betel quid)-
 Most common and ancient habit.
 Betel leaf + Pan masala.
 Pan masala - contains Tobacco + arecanut + slaked lime +
catechu + flavoring agents.

12.  Snuff
 Finely powdered form of tobacco.
 Either dry or moist- used nasally/orally.
 Carried in a metal container-a twig is dipped into it-placed
in oral vestibule.
 Snus - Moist form of snuff taken orally but is designed in
such a way that it does not require spitting.
 Zarda-
 Tobacco leaves + Slaked lime + spices – boiled in water.
 Residual tobacco – dried, coloured and flavoured.
 NO safe way to use tobacco

13. ⦁ The International Agency for Research on Cancer
(IARC) has classified both cigarette smoke and
smokeless tobacco as Group 1 carcinogens
⦁ There are 72 compounds present in smoke and listed by
International agency for research in cancer
carcinogenesis (IARC)-
◦ Groups 1 - Carcinogenic to humans.
◦ Group 2A- Probably carcinogenic to humans.
◦ Group 2B - Possibly carcinogenic to humans.
⦁ All of the compounds are carcinogenic in laboratory
animals and 15 are rated as carcinogenic to humans

14. CONSTITUENTS OF SMOKE
PARTICULATE PHASE EFFECTS
TAR (aggregate of particulate matter
minus nicotine and moisture)
Carcinogen
Polycyclic aromatic hydrocarbons (PAH) Carcinogen
Nicotine Addictive agent
Phenol Co-carcinogen, irritant
Cresol Co-carcinogen, irritant
ß – Naphthylamine Carcinogen
N – Nitroso nor nicotine (NNN) Carcinogen
Benzopyrene Carcinogen
Indole Tumor accelerated
Carbazole Tumor accelerated
Nicotine-derived nitrosamine ketone (NNK) Carcinogen

15. GAS PHASE EFFECTS
Carbon monoxide (CO) Impairs O2 transport & utilization
Hydrocyanic acid (HCN) Cilotoxin & irritant
Acetaldehyde Cilotoxin & irritant
Acrolein Cilotoxin & irritant
Ammonia Cilotoxin & irritant
Formaldehyde Cilotoxin & irritant
Oxides of nitrogen Cilotoxin & irritant
Nitrosamines Carcinogen
Hydrazine Carcinogen
Vinylchloride Carcinogen
Ethylene oxide Carcinogen

16. Formation of DNAadducts-
⦁ Carcinogens in tobacco leads to formation of DNAadducts which
then cause mutations that, if not repaired or removed, will give rise
to cell transformation processes{ altered cell cycle control} that can
lead to cancer
Induction of cyt. P450-
⦁ Cyt p 450 helps in activation of carcinogens specially PAHs and
benzenes.
⦁ Activation of these carcinogens further leads to formation of DNA
adducts, reactive O2 species and increase in oxidative stress.
⦁ Further leads to carcinogenesis.

17. Detoxification and deactivation of smoking products-
⦁ UDP-glucuronosyl transferase and Glutathione –S- transferase
helps in inactivation of smoke related carcinogens and make
them to excrete in urine.
⦁ Mutation of any of the above enzyme leads to cancer.
Impairment in DNArepair mechanism-
Impaired function of alkyl transferase.
Impaired mis-match repairs pathway.
Impaired nucleotide excision repair pathway.
Nicotine-
⦁ Have addictive effect.
⦁ Not a direct carcinogen.
⦁ Activate NF-Ƙβ that further leads to decrease in apoptosis,
increase in angiogenesis and helps in malignant transformation
of cells.

18. 3 PATHWAYS
DNAADDUCT
FORMATION -
MUTATION
GENETIC
POLYMORPHISM
ALTERATION OF CELL
CYCLE CONTROL
•By direct action on
cells to cause DNA
damage.
•Indirectly by
activation of
endogenous
mutagenic pathways
Genetic
damage
Abnormality of
metabolizing
enzymes that are
responsible for
detoxification of
tobacco derived
carcinogens ex.
UDP- glucuronosyl
transferase and
Glutathione –S-
transferase .
Impair DNA repair
mechanisms further leads
to mutations
Ex. P53, P16
and K- ras
mutations

20. Likely Carcinogen Involvement
Lung PAH, NNK (major) 1,3-butadiene, isoprene,
ethylene oxide, ethyl carbamate, aldehydes,
benzene, metals
Larynx PAH
Nasal NNK, NNN, other N-nitrosamines, aldehydes
Oral cavity PAH, NNK, NNN
Esophagus NNN, other N-nitrosamines
Liver NNK, other N-nitrosamines, furan, vinyl
chloride
Pancreas NNK, NNAL
Cervix PAH, NNK
Bladder 4-aminobiphenyl, other aromatic amines
Leukemia
(AML)
Benzene

21.  NEVER SMOKING : smoked < 100 cigarettes in a persons
life time & no current cigarette use
 FORMER SMOKING:no current cig use but having quit for
usually >1 yr
 RECENT SMOKING {RECENT QUIT}: stopped smoking with
in the recent past typically for a period of one 1 week
to 1 yr
 CURRENT SMOKING : actively smoking one or more
cigarette per day, every day or some days
PACK YEARS=no of packs of cigarettes smoked per day *no
of years smoked

22.  Effect on overall mortality-
⦁ Cancer patients who are current smokers there is increased risk
of overall mortality by 17-38%.
◦ GIT malignancy + Smoking- 60% increase in mortality.
◦ Thoracic malignancy + Smoking- 50% increase in mortality.
◦ H & N malignancy + Smoking-
🞄 Increase risk of mortality by 5 folds (RTOG-9003).
🞄 Loss of good effect of HPV in H & N cancer prognosis (RTOG-0129).
⦁ Increase in non –cancer related death 3-5 folds as compared
primary smokers due to cardiac and pulmonary
complications.

23. Effect on cancer related morbidity-
⦁ Increased risk of recurrence.
⦁ Decrease in response to treatment.
⦁ Increase in cancer related treatment toxicity.
⦁ Increase risk of development of 2nd primary.
⦁ Increase risk of progression of disease from in situ to invasive
malignancy.
Effect on patient undergone surgical treatment –
⦁ Increased risk of pulmonary complications.
⦁ Delay in wound healing
⦁ Increased risk of surgical site infections.
⦁ Prolong hospital stay.
⦁ Increased risk of DVT. and other thrombo-embolic phenomenon.

24. ⦁ Increases by 2-3 folds in patients with ca lung, H & N and ca
stomach.
⦁ Increased risk of development of lung mets in pt with ca breast
by 10 folds.
⦁ Synergistic effect in developing 2nd primary in
patients who undergone RT

25. o Smokers have decreased response rate to EGFR andALK
targeted agents.
o Smokers have increased response rate to anti-PD-1 therapy.
Effect of smoking on HPV positive patients-
⦁ Smoking vanishes the favourable outcome in patients with HPV
+ve H & N cancers.
RTOG-0129 shows-
Decrease in 3 yr OS rate in patients who were HPV positive
and smoke (90% Vs 70%)
⦁ Smoking increase the mortality rate by 5 folds.
⦁ Increased risk of 2nd primary.

26. Browman et al. did a study on H & N cancer patients who
received RT and continued to smoke, were have less likely to
have complete response to treatment.
Increased risk of treatment-related toxicities-
◦ Mucositis.
◦ Xerostomia
◦ Poor voice quality.
◦ More RT related skin changes and disfigurements.
Proposed hypothesis-
◦ Aberrant methylation of gene promoter sequences.
◦ High carboxyhemoglobin levels in smokers may modulate
tumor response to RT.

27. ⦁ More severe treatment-related toxicities-
◦ Immune suppression, weight loss, fatigue, and cardiac or pulmonary
toxicities.
⦁ Smoking may reduce the effectiveness of certain anticancer
drugs.
⦁ Poor responses to treatment and increased risk of
progression of disease as compared to non smokers.
Smoking after a cancer diagnosis negatively affects surgical
RT as well as medical treatment but smoking is not a
proven independent predictor for DFS and OS.

28.  Dependency : when we are unable to stop using a substance,
even when we know the substance is harmful to us.
 Nicotine is the main addictive agent in tobacco.
 Features suggestive of Tobacco/ Nicotine addiction-
1) Increase in tolerance to nicotine and need to increase the
dose to get the same effect.
2) Person start smoking more then usual.
3) Development of withdrawal symptoms on cessation.
4) Start postponing work & decreased interaction with society to
smoke.
5) Person start to spent more time to smoke or purchase tobacco
products.
6) Unable to stop smoking despite of knowing the health hazards.

29. ⦁ Nicotine binds to nicotinic receptors (α4β2 nicotinic
receptors) in ventral tegmental area (Mesolimbic system).
⦁ This leads to increase in extracellular concentrations of
Dopamine in the Nucleus accumbens.
⦁ This increase in extracellular dopamine in the nucleus
accumbens results in short term feel of reward or
satisfaction.
⦁ To achieve this short term feel of reward or satisfaction
peoples smoke again and again to maintain high dopamine
levels in mesolimbic dopaminergic system.

30. Symptoms start with in first few hrs to days and reaches to
peak over 2-4 wk
 Intense craving for nicotine/ tobacco.
 Diaphoresis.
 Depressed mood.
 Anger.
 Irritability & impatience.
 Anxiety.
 Restlessness & altered sleep.
 Decrease in HR
 Increase in weight / hunger.

31. ⦁ To measure the exposure of smokers to the carcinogenic
components of tobacco.
⦁ Most of times urine, blood, saliva or expired air are used as
samples to measure tobacco carcinogen biomarker.
⦁ Mostly DNA adducts, protein adducts and blood or urine
metabolites/ by products of tobacco used as biomarkers.
⦁ DNAadduct measurements is most direct evidence concerning
the extent of DNA damage in a person who uses tobacco
products.

32. USES OF MEASUREMENT OF TOBACCO CARCINOGEN
BIOMARKERS
Critical in the studies related to tobacco and its relation with
cancer.
To evaluate a new tobacco products that comes in market with
claims of low carcinogenicity and toxicity.
Used to evaluate the exposure of non-smokers to second
hand smoking. Eg. total NNAL.
Measurement of individual susceptibility to effect of tobacco.
To predict which smoker may get cancer in future which may
be very useful in cessation efforts.

34. US –PHS smoking cessation guidelines gives Five ‘A’strategy-
Primary steps in clinical practice for smoking cessation includes:
 Ask and document use of tobacco by patient in terms of type, amount,
urge to smoke and duration.
 Advise every patient to quit smoking.
 Assess the willingness of the patient to attempt quitting.
 Assist the patient to quit smoking using behavioral therapy and
pharmacotherapy .
 Arrange follow-up with patient after quitting.

35.  obtain a detailed smoking history
• assessing the amount smoked
• the number of attempts at quitting
• aids used including medications (varenicline,
bupropion, nicotine replacement therapy [NRT]),
support groups, and behavior therapy.
 The changes in the smoking history should be
frequently updated in the health record and reflect the
attempts as well as the interventions utilized.
 If they failed on one pharmacologic or behavioral
intervention in the last 30 days, they can continue it as
it may require multiple attempts to achieve success.
 continually advise the patient and offer support
irrespective of the number of failed attempts to effect
eventual success.

36.  Primary therapy: First-line preferred regimens include NRT and
varenicline (combination NRT is superior to single forms of
NRT)
 Varenicline -partial agonist of the alpha4beta2 subtype of the
nicotinic acetylcholine receptor.
Dosage
 0.5 mg/day on days 1 to 3
 0.5 mg twice per day on days 4 to 7
 maintenance with 1 mg twice per day for 11 weeks (total of 12
weeks of treatment)
 Subsequent therapy : 2 nd line therapy or i1 st line in pts with
depression or anxiety ( Bupropion in combination with NRT
).bupropion dosage 150 mg OD *3 days f/b BID .SHOULD BE

37.  Aminimum of 12 wk of combination NRT /Varenicline
therapy is recommended.
 Therapy may extend from 6 month upto 1 yr.
 Dose tapering must be done slow, over a period of 10 wk.
 Follow up of patient may be done “in person or” with in 2wk of
starting treatment and telephonically additional follow ups
should be done at an interval of 3 months.
 Nicotine withdrawal symptoms reaches to the peak at around 2
wks of quitting . This is most important time period to be taken
care by behaviour therapy.

38.  pharmacologic therapy is the most effective when combined with behavioural
therapy
 tailored to the patient’s nicotine dependence and previous quit attempts, provides
strategies for: Coping with nicotine withdrawal symptoms and cravings (Note:
Symptoms typically peak between 48–72 hours after quitting, and last about 2–3
weeks before subsiding.)
 Identifying what triggers them to smoke (eg, coffee, alcohol, social situations, stress)
 Coping with stressful and difficult situations in which smoking is likely
 Avoiding high-risk situations
 Treatment for smoking should be offered as an integral part of oncology
treatment and continued throughout the entire oncology care continuum,
including surgery, radiation therapy, systemic therapy, and end-of-life care

39.  battery-operated devices used to inhale an aerosol, typically
containing nicotine, flavorings, and other chemicals.
 produce an aerosol by heating a liquid that usually contains
nicotine—the addictive drug in regular cigarettes, cigars, and
other tobacco products—flavorings, and other chemicals that help
to make the aerosol.
 Nicotine in e-liquids absorbed from the lungs systemically
stimulates the adrenal glands to increase epinephrine. Epinephrine
increases central nervous system (CNS) levels of dopamine,
which reinforces and rewards the use of nicotine
NOT RECOMEENDED FOR SMOKING CESSATION

41. Heat not burn tobacco cigarette-
⦁ Electrical blade heats tobacco stick to much lower temperature than a
normal cigarette.
⦁ Generate flavoured nicotine containing vapours.
⦁ Nicotine content is about 80% of traditional cigarette.
⦁ Low amount of other harmful carcinogens.
⦁ As per WHO, not less harmful then conventional cigarette.

42.  hypnosis, acupuncture, nutritional
supplements-- incomplete evidence

43. •Smoking increases the risk of pulmonary complications, surgical site infection, and poor
wound healing in patients undergoing surgery
•<7 days to surgery-combination NRT preffered (cat. 1)
•≥7 days to surgery-combination NRT /Varenicline (cat.1)
•Longer the period of smoke cessation better the surgical outcome.
• Patients should be encouraged to quit smoking as soon as possible before surgery,
regardless of how short the time is to surgery.
• Longer periods of abstinence from smoking confer better surgical outcomes but should
not delay appropriate timing for cancer resection