Influence of smoking in the glutathione-S-transferase M1 deficiency - associated risk for squamous cell carcinoma of the bladder in schistosomiasis patients in Egypt

Abstract

Summary In this study we show an effect of the glutathione-S-transferase MI (GSTM1) null phenotype on the risk for squamous cell carcinoma (SCC) of the bladder among male smokers in Egypt, with an adjusted odds ratio of 4.8 (95% confidence interval:1.06-21.77). However, no overall effect of the GSTM1 null phenotype on the risk for bladder SCC was observed.Keywords: glutathione-S-transferase; bladder cancer; schistosomiasis; free radical Carcinoma of the urinary bladder is the most common malignancy in many tropical and subtropical countries. There is a well-documented association with chronic urinary schistosomal infection, resulting in squamous cell carcinoma of the bladder (SCC), which is a major cause of morbidity and mortality in the endemic areas (IARC, 1994). Furthermore, foreign compounds from tobacco smoking may be involved in up to 50% of bladder cancers (transitional cell carcinoma, TCC) in western populations (Cole et al., 1971), through metabolic intermediates, most of them probably oxidised metabolites from N-nitroso-compounds, aromatic amines and polycyclic aromatic hydrocarbons (IARC, 1986;Wynder and Goldsmith, 1977).Glutathione-S-transferase Ml (GSTM 1) detoxifies various carcinogenic electrophiles including epoxides. A protective role against neoplasias associated with smoking has, therefore, been attributed to it. GSTM 1 has polymorphic expression and about half the population in various racial groups lack it (Hussey et al., 1986). Indeed, a greater susceptibility to lung (Seidegard et al., 1990) and larynx cancer (Lafuente et al., 1933) has been shown among smokers lacking GSTM1. Susceptibility to bladder cancer has also been studied, although only transitional cell carcinoma has been considered (Zhong et al., 1993;Lafuente et al., 1993;Bell et al., 1993;Daly et al., 1993;Brockmoller et al., 1994;Lin et al., 1994). Some of these studies found a protective effect of GSTM1 in bladder cancer (Table I).We, therefore, designed a study to determine whether GSTM1 deficiency may confer susceptibility to the squamous cell carcinoma of the bladder associated with schistosomiasis. Our hypothesis is based on the antioxidant properties of this isoenzyme, which is able to metabolise the hydroperoxides of DNA that may be produced in chronic inflammation (Ketterer and Meyer, 1989;Lafuente et al., 1995). Although SCC of the bladder is not known to be related to smoking, we have attempted to assess the influence of the smoking habit on this carcinogenic process, given the role of the GST system in the metabolism of the toxic products of tobacco. Materials and methodsEighty bladder SCC patients were recruited at the Urology Department of the University of Assiut, Egypt, between 1993 and 1994; 66 patients were men (mean age 45.2+6.5 years) and 14 were women (mean age 41.0+7 years). All had histologically proven SCC of the bladder and none had received prior chemotherapy or radiotherapy. All tumours were deeply invasive (pT3 and pT4).Seventy unrelated control individuals (C) without clinical or histological evide...

GSTM1, GSTT1 Null Variants, and GPX1 Single Nucleotide Polymorphism Are Not Associated with Bladder Cancer Risk in Egypt

“…Previous studies have found that the GSTM1 null genotype is associated with an increased risk of bladder cancer overall, among SH-infected individuals (4), and among male smokers (5). Conversely, other studies have reported increased risk in women but not men, and among women, only among smokers (6), as well as no overall association with increased risk (7).…”

Tobacco smoking in Egypt: a scoping literature review of its epidemiology and control measures

“…A case-control study by Lafuente et al (36) showed that smokers with metabolic deficiency, namely Glutathione S-transferase Mu1, have a 4.8 fold increase in the risk of developing squamous cell carcinoma (SCC) of the bladder. Makhyoun et al (37) performed a case-control study that found the frequency of heavy smoking was 32.2% for bladder cancer patients, compared with 14.9% in the control group.…”

Association of Glutathione S-transferase gene polymorphism with bladder Cancer susceptibility

“…In the subgroup of patients and controls who smoked cigarettes, we included 24 studies [ 25 , 30 , 34 , 35 , 42 , 43 , 47 , 48 , 50 , 51 , 54 – 56 , 64 , 65 , 68 , 69 , 73 , 76 , 83 , 85 , 91 , 92 , 95 ] (data not shown) containing 3724 case series and 3160 controls. Average distribution frequency of the GSTM1-null genotype was 55.67% in the bladder cancer group and 47.57% in the control group, indicating that the GSTM1-null genotype was significantly higher in the bladder cancer cases compared with the controls (case/control = 1.17).…”