The relative risk of

cancer from smoking

and vaping nicotine
Presented at Medical Ground Rounds,
Prince of Wales Hospital, Sydney, Australia
22 November 2023
Dr Colin Mendelsohn. Founding Chairman, Australian Tobacco Harm Reduction Association
Disclosure: no payments or benefits from vaping or tobacco companies
 Overview

• Assessing the relative carcinogenicity of smoking and vaping in the

absence of long-term epidemiological studies
Key carcinogens Cancer
Carcinogenicity = present + potency + Exposure

Compare smoke and vapour

• Modelling studies
• Expert opinion

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 Constituents of smoke and vapour

Tobacco smoke Vapour

• >7,000 chemicals in high doses 1 • 100-150 chemicals in low doses 2,3
• Combustion of tobacco, 9000 C • Heating liquid, 3000 C liquid aerosol
• solid particles, gases, liquids • No combustion or tobacco

1. US DHHS 2010 2. Margham J. Chem Res Toxicol 2016 3. Nicol J. Chem Res Toxicol 2020
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 1. Key carcinogens in smoke

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 Carcinogens in tobacco smoke

• Over 70 known carcinogens

• 16 classified as carcinogenic to humans (group 1 carcinogens)

1. Tobacco smoking and carcinogenic risk to humans. IARC Monograph 100E. IARC 2012
2. IARC: Agents Classified by the IARC Monographs, Volumes 1 – 134. IARC Monogr. 2020
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 Most important carcinogens in tobacco smoke

Carcinogen Examples Cancer types

* Polycyclic aromatic Benzo(a)pyrene Lung, larynx, oral, cervix
hydrocarbons (PAH) Dibenz(a,h)antracene
* Tobacco Specific NNN Lung, nasal, oral, oesophagus,
n-Nitrosamines (TSNAs) NNK liver, pancreas, cervix
* Aromatic amines 2-naphthylamine; 4-aminobiphenyl Bladder
Volatile organic compounds 1,3-butadiene; benzene Lung, leukemia
Aldehydes Formaldehyde; Acetaldehyde Lung, nasal
Other organics Ethylene oxide Lung, lymphatic, blood

[group 1 carcinogens]

1. International Agency for Research on Cancer 2012 2. US Department of Health and Human Services. US Surgeon-General 2010
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 Nicotine

• Not a carcinogen 1, 2, 3, 4, 5
• 80% of US physicians believe it is 6
• Laboratory studies: tumour progression, pro-metastatic 7-10
‒ In vitro, animal studies: cell proliferation, inhibits apoptosis, induces cell migration and
invasion, induces angiogenesis, inhibits immune functions, intracellular signalling
• May reduce effectiveness of chemo and radiotherapy 10

1. IARC 2012 2. US DHHS 2010 3. US NASEM 2018 4. Royal College of Physicians 2016 5. Haussman H. Crit Rev Tox 2016
6. Steinberg M. Gen Intern Med 2020 7. Schaal C. Mol Cancer Res 2014 8. Grando S. Nature Rev 2014 9. Sanner T. Front Oncol
7 2015 10. Warren J. J Carcinogen 2013
 2. Cancer potency

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 Cancer potency of inhaled toxicants

• Established for environmental and occupational exposure

• California Office of Environmental Health Hazard Assessment (OEHHA) 1

• US Environmental Protection Agency 2

1. California Office of Environmental Health Hazard Assessment (OEHHA). 2009 2. USEPA. An Overview of Methods for EPA’s
National-Scale Air Toxics Assessment: US Environmental Protection Agency. Office of Air Quality, Planning, and Standards 2011.
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 3. Exposure to carcinogens

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 “The dose makes the poison”

• “the level of toxins, rather than

their presence, is the most
important determinant of how
harmful a product is to
humans” 1

1. Royal College of Physicians 2016

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 Measuring exposure

• Measure in the body vs in smoke/vapour

• Most carcinogens are not directly measurable in the body
• Most metabolised to active intermediate agents (“biomarkers”) 1
‒ NNK NNAL
‒ 1,3-butadiene MHBMA
‒ Benzene S-PMA
• Biomarkers measured in urine and blood
• Reliable for estimating exposure and potential health risk 1

1. US DHHS 2010
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 1. Polycyclic Aromatic Hydrocarbons (PAHs)
Benzo(a)pyrene; Dibenz(a,h)antracene

• Source: incomplete combustion

• Level of 10 PAH metabolites in vapers
“Not distinguishable from non-users” 1
• Of 7 PAH biomarkers in vapers 2
‒ 5 were the same as never-users
‒ All significantly lower than smokers

1. Scherer G. Arch Tox 2022 2. Wang Y. Env Int 2019

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 2. Tobacco-Specific n-Nitrosamines (TSANs)
NNN, NNK

• Source: curing tobacco

• “Levels of TSNAs were similar when comparing people who switched
from smoking to vaping, to those who switched to no use of nicotine
products, in longitudinal studies”
‒ Review of 22 studies
• “Observed average reductions in biomarker levels of tobacco-specific
nitrosamines, may result in levels which are similar to those
measured in non-users”
‒ Comprehensive review

1. Taylor E. Nic Tob Res 2023 2. Office of Health Improvement and Disparities, England 2022
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 3. Volatile organic compounds
1,3-butadiene and benzene

• Source: incomplete combustion of organic compounds

• Review of all the available evidence
‒ Vapers have 1,3-butadiene and benzene levels “like never-users”

Goniewicz M. Addiction Neuroscience 2023

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 4. Aromatic amines
2-naphthylamine, 4-aminobiphenyl

• Combustion products

No significant difference between

vapers and non-users (72h)

No significant difference after

switching from smoking to
vaping compared to complete
abstinence (6 d)

1. Scherer M. ACS Omega 2022 2. Cohen G. Nic Tob Res 2021

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 5. Aldehydes
Formaldehyde, acetaldehyde (not biomarkers)

Ref Devices tested Comparison to smoke

Formaldehyde Acetaldehyde
1 Juul 70x 1,000x
2 Relx (4) 30 - 260x 3,100 – 4,420x
3 E-liquids (2) 5 - 31x 191 - 528x
4 NHOSS (3) 4 – 42x 101 – 495x

• “Aldehydes…have been found at very low levels that are unlikely to

represent a serious risk to health” 5

1. Mallock N. Arch Tox 2020 2. Xu T. Drug Test Anal 2022 3. Farsalinos K. Food Chem Tox 2018 4. Dusautoir R. J Haz Mat 2020
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5. UK National Centre for Smoking Cessation and Training 2023
 6. Ethylene oxide

• Levels of HEMA (biomarker) in vapers

same as for NRT users
‒ Cross-sectional study of long-term
smokers and vapers (≥6 months)
n=181

1. Shahab L. Annals Int Med 2017

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 Flavouring agents

• Limited safety data for inhalation

• “To date, there is no clear evidence that specific flavourings pose health
risks” 1
• Some may carry some risk, eg cinnamaldehyde, diacetyl
• More research needed

1. Public Health England, report 2018

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 4. Modelling

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 Modelling the relative risk of cancer: vaping vs cancer

Carcinogens in
smoke/aerosol

Cancer potency 1,2

Modelling Lifetime
studies cancer risk
Exposure
Concentrations
Daily volume

1. Tobacco smoking and carcinogenic risk to humans. IARC Monograph 100E. IARC 2012
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2. IARC: Agents Classified by the IARC Monographs, Volumes 1 – 134. IARC Monogr. 2020
 Modelling cancer risk

• All modelling studies predict that the lifetime risk of cancer from vaping
will be substantially less than from smoking
Risk compared
Study Measure to smoking
1 Stephens Lifetime cancer risk 0.4%
2 Murkett Lifetime cancer risk 0.23%
3 Rodrigo Lifetime cancer risk from a closed vape system 0.9-1.4%
4 Scungio Lifetime lung cancer risk 50,000 times less
5 Avino Lifetime lung cancer risk from second-hand vapour 50,000 times less

1. Stephens W. Tob Control 2017 2. Murkett R. F1000Research 2022 3. Rodrigo G. Arch Tox 2020 4. Scungio M. J Aerosol Sci 2017
22 5. Avino P. Sci Tot Env 2018
 5. Expert opinion

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 Expert opinion
-

Cancer Council “E-cigarettes expose users to chemicals and toxins at levels that have
Australia 1 the potential to cause health effects”
Cancer Research UK 2 “There is no good evidence that vaping causes cancer”
NASEM 3 “There is little evidence that e-cigarettes pose significant cancer risk”
UK National Centre for “Modelling reveals that the cancer risk for people who vape is
Smoking Cessation and
Training 4 considerably lower than for those who smoke”

American Association “Vaping exposes the user to carcinogens and therefore likely increases
for Cancer Research long-term cancer risk, but for most carcinogens at levels far lower than
and the American from smoking combustible tobacco cigarettes. The magnitude of long-
Society of Clinical term health risks will remain unknown until longitudinal studies are
Oncology 5 completed”

1. Cancer Council Australia. 2020 2. Cancer Research UK 2023 3. US National Academies of Sciences, Engineering, Medicine 2018
4. UK National Centre for Smoking Cessation and Training 2023 5. Herbst RS. ENDS. An updated policy statement from the AACR and
the ASCO 2022
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 Conclusion

• Vaping is not risk-free

• Key carcinogens in smoke are in far lower doses in vapour

• Additional chemicals are present in vapour

• Based on dose and cancer potency of carcinogens present:
Switching from smoking to vaping nicotine substantially reduces lifetime
cancer risk

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