MOLECULAR CARCINOGENESIS BRIEF COMMUNICATION Role of GSTT1 and M1 Null Genotypes as Risk Factors for B-Cell Lymphoma: Influence of Geographical Factors and Occupational Exposure Javier Ruiz-Cosano, 1 Pablo Conesa-Zamora, 2 * Rocı´o Gonza ´ lez-Conejero, 3 Elena Pe ´ rez-Ceballos, 4 AntonioMartı´nez-France ´ s, 5 Vicente Vicente, 4 and Miguel Pe ´ rez-Guillermo 2 1 Clinical Analysis Department, Hospital Universitario Santa Marı ´a del Rosell (HUSMR), Cartagena, Spain 2 Molecular Pathology and Pharmacogenetic Group, Pathology Department, HUSMR, Cartagena, Spain 3 Department of Medicine, Centro Regional de Hemodonacio ´n, Murcia, Spain 4 Haematology Department, Hospital General Universitario Morales Meseguer (HGUMM), Murcia, Spain 5 Haematology Department, HUSMR, Cartagena, Spain The interrelationship between genetic susceptibility and carcinogenic exposure is important in the development of haematopoietic malignancies. Both factors need to be considered to enable assessment of disease risk associated with a given individual under certain environmental conditions. GSTT1 and GSTM1 are two genes whose proteins are involved in the detoxification of potential carcinogens. We have studied the prevalence of GSTT1 and GSTM1 null polymorphisms using a novel PCR multiplex protocol in a group of 158 patients with B-cell lymphoma (BCL, 138 with non-Hodgkin lymphoma and 20 with Hodgkin lymphoma) and 214 healthy controls. A questionnaire regarding occu- pational exposure and lifestyle factors was also completed by both groups. GSTM1 null genotype showed no signifi- cant differences between patients and controls (46.9% and 55.6%, respectively). In contrast, GSTT1 null genotype was observed in 25.3% of patients and 15.4% of controls (P ¼ 0.013; OR ¼ 1.85; CI (95%):1.11–3.09), suggesting a role for the GSTT1 null genotype in the development of BCL. This effect was even more evident in females (27.5% vs. 14%: P ¼ 0.014). No significant association was observed between GST genotypes and disease risk in relation to smoking or occupational exposure. ß 2011 Wiley-Liss, Inc. Key words: GSTT1; GSTM1; polymorphism; lymphoma; susceptibility INTRODUCTION The development of B-cell lymphoma (BCL) including Hodgkin’s (HL) and non-Hodgkin’s lymphoma (NHL) is, to a great extent, the result of a combined effect of genetic susceptibility and environmental factors. Xenobiotic metabolizing enzymes play a role in the detoxification of poten- tial carcinogens as well as endogenous com- pounds. Glutathione S-transferase family members including GSTT1 and GSTM1 are also involved in the conjugation of environmental pollutants such as polyaromatic hydrocarbons and certain antineo- plastic drugs [1]. The null genotype in both GSTT1 and GSTM1 leads to a loss of the corresponding protein due to homozygous gene deletion. These genotypes have been extensively studied in cancer susceptibility and prognosis [2]. The relationship between GST null genotypes and lymphoma treatment-related adverse effects and prognosis has been investigated [3–5] and the few studies that have addressed their role in lymphoma susceptibility have given conflicting results [1,6–13]. With respect to environmental exposure as a risk factor for BCL, a considerable body of evidence has demonstrated that pesticide exposure may increase the risk of NHL [14,15], whilst the association for chemical industry compounds remains controver- sial [16–18]. Additional Supporting Information may be found in the online version of this article. Abbreviations: BCL, B-cell lymphoma; HL, Hodgkin’s; NHL, non- Hodgkin’s lymphoma. Javier Ruiz-Cosano and Pablo Conesa-Zamora contributed equal- ly to the work. *Correspondence to: Pathology Department, Santa Marı´a del Rosell University Hospital, Paseo Alfonso XIII, 61, 30203 Cartagena, Spain. Received 30 November 2010; Revised 6 May 2011; Accepted 12 May 2011 DOI 10.1002/mc.20814 Published online in Wiley Online Library (wileyonlinelibrary.com). ß 2011 WILEY-LISS, INC.