Rapid Responses to:

PAPERS: Jeffrey E Harris, Michael J Thun, Alison M Mondul, and Eugenia E Calle Cigarette tar yields in relation to mortality from lung cancer in the cancer prevention study II prospective cohort, 1982-8 BMJ 2004; 328: 72 [Abstract] [Full text]

Rapid Responses: Submit a response to this article

Rapid Responses published:

DNA Adducts in Smokers

John M McLaren Howard   (14 January 2004)

The answer to a quandary?

Alfred P J Lake   (18 January 2004)

DNA Adducts in Smokers 14 January 2004
John M McLaren Howard, Laboratory Director Biolab Medical Unit Send response to journal: Re: DNA Adducts in Smokers	Dear Sir, An excellent paper you recently published (1) demonstrates similar cancer risk in people who smoke medium, low and very low tar cigarettes. This raises questions about smoking-related cancer causes that are additional to tar components. Nitrosamine-DNA adducts have certainly been shown in smokers. Many important papers on this topic can be found in references (2) and (3). In a recent study (4) we were able to confirm this in 13/14 smokers. However, 8/14 of the smokers also had nickel-DNA adducts and 11/14 had cadmium-DNA adducts. Both nickel and cadmium are concentrated by the tobacco plant and nickel is a known carcinogen. I am unable to find any data to show reduced nickel and/or cadmium in low tar cigarettes. The toxic metal DNA burden and especially the nickel adducts may be additional risk factors for lung cancer in smokers. Another concern from the results of our study is that 11/74 non- smokers with no specific history of toxic metal exposure had nickel-DNA adducts and 9/74 had cadmium-DNA adducts. A larger study is needed to explore this area of cancer risk that may well offer an explanation for similar lung cancer rates in smokers of medium and low tar cigarettes. 1) Harris JE, Thun MJ, Mondul AM, Calle EE. Cigarette tar yields in relation to mortality from lung cancer in the cancer prevention study II prospective cohort, 1982-8. BMJ 2004; 328: 72-6. 2) Hemminki K, Dipple A, Shuker DEG, Kadlubar FF, Segerback D, Bartsch H. DNA Adducts: Identification and Biological Significance. IARC Scientific Publications no. 125. Lyon, France: International Agency for Research on Cancer, 1994. 3) Singer B, Bartsch H. Exocyclic DNA Adducts in Mutagenesis and Carciogenesis. IARC Scientific Publications no. 150. Lyon, France: International Agency for Research on Cancer, 1999. 4) McLaren Howard J. The Detection of DNA Adducts (Risk Factors for DNA Damage). A Method for Genomic DNA, the Results and Some Effects of Nutritional Intervention. Journal of Nutritional and Environmental Medicine 2002; 12: 19-31 Competing interests: None declared
The answer to a quandary? 18 January 2004
Alfred P J Lake, Consultant Anaesthetist Glan Clwyd Hospital, Rhyl LL18 5UJ Send response to journal: Re: The answer to a quandary?	Despite being an ex-smoker myself I am one of those who remain less than convinced about some dangers of passive smoking in support of which little good science appears to exist and am concerned that the current raft of proposals to restrict the activities and civil liberties of smokers is a ‘bridge too far’. I read this article with great interest as I believe that it may suggest the answer to a long-standing quandary which the authors did not highlight. The authors’ suggestion that compensatory smoking was the reason for no difference in risk being demonstrated between those who smoked medium, low or very low tar cigarettes is only one possible explanation for the findings. The consistent observation of the many examples of ‘Uncle Fred’ who smoked heavily all his life and was fit as a flea until he passed on in his sleep aged 90 should make us ask why did he neither get carcinoma of the lung, despite the wholesale application of carcinogenic paint, nor elsewhere to kill him; in other words, was he simply good at immunosurveillance? Should the range of tars in cigarettes be equated with an equivalent range of risk or are some individuals simply at risk for the development of any sort of carcinoma due to poor defence mechanisms when the threshold of carcinogen load is exceeded for example in very low tar brands, perhaps through passive smoking or even diet? What about the incidence other cancers in these and other patients? Carcinoma of the lung with its smoking connection is very emotive but perhaps rather than attempt to eradicate all passive smoking we should get real and look more closely at the immune surveillance systems of ‘Uncle Fred’ and his kind to the future benefit of all. Competing interests: None declared