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4-Aminobiphenyl-Hemoglobin Adducts and Risk of Smoking-Related Disease in Never Smokers and Former Smokers in the European Prospective Investigation into Cancer and Nutrition Prospective Study

¹ Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri; ² Genetics Research Institute; ³ Department of Epidemiology, National Cancer Institute, Milan, Italy; ⁴ Imperial College London, London, United Kingdom; ⁵ University of Torino, ⁶ ISI Foundation, Turin, Italy; ⁷ Institute of Public Health, University of Aarhus, Aarhus, Denmark; ⁸ Department of Oncology, ⁹ Strangeways Research Laboratory, University of Cambridge, Cambridge, United Kingdom; ¹⁰ IARC, Lyon, France; ¹¹ Department of Environmental and Occupational Health, Utrecht University; ¹² Julius Center for Health Sciences and Primary Care, University Medical Center, Utrecht, Netherlands; ¹³ WHO, European Centre for Environment and Health, Bonn, Germany; ¹⁴ Department of Clinical Epidemiology, Aalborg Hospital, Aarhus University Hospital, Aalborg, Denmark; ¹⁵ Institute of Cancer Epidemiology, Danish Cancer Society, Copenhagen, Denmark; ¹⁶ Institut National de la Sante et de la Recherche Medicale U521, Institut Gustave Roussy, Villejuif, France; ¹⁷ Division of Clinical Epidemiology, Deutsches Krebsforschungszentrum, Heidelberg, Germany; ¹⁸ German Institute of Human Nutrition, Potsdam-Rehbücke, Germany; ¹⁹ Department of Hygiene and Epidemiology, Medical School, University of Athens, Athens, Greece; ²⁰ Molecular and Nutritional Epidemiology Unit and ²¹ Cancer Risk Factor Branch, Molecular Biology Laboratory, CSPO-Scientific Institute of Tuscany, Florence, Italy; ²² Cancer Registry Azienda Ospedaliera Civile-M.P. Arezzo, Ragusa, Italy; ²³ Dipartimento di Medicina Clinica e Sperimentale, Università Federico II, Naples, Italy; ²⁴ Centre for Nutrition and Health, National Institute for Public Health and the Environment, Bilthoven, The Netherlands; ²⁵ Institute of Community Medicine, University of Tromso, Tromso, Norway; ²⁶ Department of Epidemiology, Catalan Institute of Oncology, Barcelona, Spain; ²⁷ Andalusian School of Public Health, Granada, Spain; ²⁸ Department of Public Health of Guipuzkoa, San Sebastian, Spain; ²⁹ Public Health Institute, Navarra, Spain; ³⁰ Epidemiology Department, Regional Health Council, Murcia, Spain; ³¹ Public Health and Health Planning Directorate, Asturias, Spain; ³² Malmö Diet and Cancer Study, Lund University, Malmö, Sweden; ³³ Department of Public Health and Clinical Medicine, Umeå University, Umeå, Sweden; and ³⁴ Cancer Research UK Epidemiology Unit, University of Oxford, United Kingdom

Requests for reprints: Luisa Airoldi, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri, Via Eritrea 62, 20157 Milan, Italy. Phone: 39-0239014456; Fax: 39-0239001916. E-mail: airoldi{at}marionegri.it

The aim of this study was to evaluate whether biomarkers of environmental tobacco smoke exposure [i.e., 4-aminobiphenyl-hemoglobin (4-ABP-Hb) adducts] were predictive of the risk of tobacco-related cancers and diseases. We did a case-control study nested within the European Prospective Investigation into Cancer and Nutrition, involving 190 controls and 149 cases (incident cancer of the lung, bladder, pharynx, larynx, oral cavity, leukemias, and chronic obstructive pulmonary disease or emphysema deaths). All individuals were never smokers or ex smokers for >10 years. 4-ABP-Hb adducts were analyzed in peripheral blood collected before the onset of the disease (median, 7 years). Overall, 4-ABP-Hb adducts were higher, although not statistically significantly so, in cases (as a whole) than controls. In the control population, high fruit and vegetable consumption significantly lowered the frequency of detectable adducts (Fisher's exact test, P = 0.025). Restricting the analysis to women, 4-ABP-Hb adducts were higher in cases than controls (Mann-Whitney P = 0.036) and the odds ratio (OR) for the presence/absence of adducts was 2.42 [95% confidence interval (95% CI), 1.18-4.98]. Moreover, the association of adducts with the individual cancer types was stronger in women than in the whole study population, although statistically significant only for leukemias (OR, 2.77; 95% CI, 1.06-7.20). The results provide some evidence that women may be more susceptible to environmental tobacco smoke, as suggested by their higher adduct levels. The most important finding of this prospective study is that, at least in women, 4-ABP-Hb adducts may help identify subjects at high risk of cancers related to environmental tobacco smoke exposure.

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