While the link between lung cancer and second-hand smoke (SHS) has been established for many years, the extent of the risk remains a subject of much debate. Screening for biological markers specific to SHS and related to lung cancer could be a more reliable approach to establishing this risk level. The issues are discussed in a Review in the July edition of The Lancet Oncology, authored by Dr Ahmad Besaratinia and Dr Gerd Pfeifer, Beckman Research Institute of the City of Hope National Medical Center, Duarte, CA, USA. The edition is dedicated to lung cancer and will be presented at the International Lung Cancer Conference, Liverpool, UK, from 9-12 July.
Mainstream smoke is generated during puff drawing from the burning cone and hot zone of a tobacco product, which travels through the filter or outward mouthpiece. Sidestream smoke is emitted from the smouldering coal of a tobacco product into the air between puffs. The same carcinogens and chemicals found in mainstream smoke are found in SHS, but in different quantities due to mixing and dilution with air. Smokers, who actively inhale very large doses of mainstream smoke-carcinogens, have a higher intake of carcinogens than SHS-exposed individuals. However, the finding that sidestream smoke-condensate is more potent than mainstream smoke-condensate in inducing mouse skin tumours suggests that SHS imposed on non-smokers might be even more carcinogenic than mainstream smoke inhaled by active smokers.
Many compounds in smoke are carcinogenic due to their ability to generate substances capable of forming DNA lesions, known as DNA adducts. Many genotoxic carcinogens are known to leave unique signatures on cancer-related genes -- in the form of specific mutations at specific locations. A technique called DNA-lesion footprinting* in conjunction with mutagenicity analysis** is currently used to find these carcinogen signatures. The authors propose that this technique be used in cancer-relevant genes, which are commonly mutated in smoke-related lung cancer. In fact, this approach has already been used successful to find adducts connected with various smoke-derived carcinogens, including polycyclic aromatic hydrocarbons.
Other key issues awaiting the further exploration include the determination of the type, frequency, and distribution of DNA lesions in cancer-related genes consequent to SHS exposure in non-smokers compared with those caused by mainstream smoke in smokers. This would help determine whether lung cancer development in smokers versus non-smokers exposed to SHS is merely a question of smoking dose -- ie, to verify whether the differing risk of lung cancer development is only dependent on smoking dose since SHS is still only cigarette smoke. However, chemical and biological evidence suggests that sidestream smoke, the main component of SHS, is different from mainstream smoke inhaled by active smokers.
It is also important to investigate whether SHS can cause lung cancer through an epigenetic pathway. This pathway is defined as heritable modifications to a person’s DNA with the potential to change gene regulation and how it is packaged with the cell, without actually changing the primary DNA sequence, ie, the order in which the DNA molecules are arranged. Therefore, individuals chronically exposed to SHS will need to be analysed to determine whether SHS induces lung cancer through an epigenetic pathway.
The authors conclude by discussing the difficulties of establishing the link between SHS and cancer when humans are continuously exposed to whole range of other environmental carcinogens present in food, drinks, and the ambient air. The variability, composition and concentration of SHS further complicate matters. They say: "Although the causal link between SHS exposure and lung-cancer development is well established, the estimated risk for lung cancer development consequent to SHS exposure remains somewhat debatable. Elucidation of the mechanisms of SHS action that are relevant to carcinogenesis can help identify unique biological markers that can be used for assessing lung cancer risk in relation to SHS exposure."
Notes to editors:
*DNA-lesion footprinting: a technique to locate the site of DNA damage
**mutagenicity analysis: a technique for investigating changes in the primary DNA sequence
Dr Ahmad Besaratinia and Dr Gerd Pfeifer, Beckman Research Institute of the City of Hope National Medical Center, Duarte, CA, USA T) +1 626 256 4673 ext: 65918 E) ania@coh.org / abesaratinia@coh.org
Alternative contact Roya Alt, Senior Director, Public Relations T) +1 800-544-3541 E) ralt@coh.org
http://eurekalert.org/jrnls/lance/pdfs/TLOshsfinal.pdf
Journal
The Lancet Oncology