Polymorphisms of drug-metabolizing enzymesCYP1A1,GSTTandGSTPcontribute to the development of diffuse large B-cell lymphoma risk in the Saudi Arabian population

Abstract

The last four decades have seen significant increase in the incidence of non-Hodgkin lymphoma (NHL) as a possible result of increasing environmental carcinogens exposure. Based on the increasing evidence for the association between carcinogen-exposure-related cancer risk and xenobiotic gene polymorphisms, we have undertaken a hospital based case-control study on xenobiotic gene polymorphisms in Saudi individuals with a diagnosis of diffuse large B-cell lymphoma (DLBCL). Polymorphisms in five genes (CYP1A1, GSTT1, GSTP1, GSTM1, and NQO1) were characterized in 182 individuals with DLBCL and 513 normal controls using PCR-RFLP method. The CYP1A1*2C (p = 0.011, OR: 6.62, and 95% CI: 1.56-28.10), GSTT1 null (p < or = 0.001, OR: 11.94, 95% CI: 7.88-18.12), and GSTP1 TT genotypes (p = 0.017, OR: 3.42, 95% CI 1.26-9.38) demonstrated significant association of DLBCL risk. None of the other alleles tested for proved to be significant indicators of DLBCL risk. Our findings suggest that polymorphisms of xenobiotic metabolizing enzyme genes may modify the individual susceptibility to develop DLBCL in Saudi Arabian population.

The link between genetic polymorphism of glutathione-S-transferases, GSTM1, and GSTT1 and diffuse large B-cell lymphoma in Egypt

“…Calculation of the risk estimate revealed that GSTM1 null genotype was not associated with DLBCL risk. This is in accordance with many previous studies (Al Dayel et al 2008;Sarmanova et al 2001;Kerridge et al 2002;Chiu et al 2005). On the other hand, the study of Gra et al (2002) reported that the GSTM1 null genotype correlates with increased risk of NHL.…”

“…In our study, dual null genotype was detected in 23.9 % of DLBCL patients. This is consistent with that previously reported by Al Dayel et al (2008) and Kerridge et al (2002). Dual null genotype was signiWcantly higher in DLBCL patients compared to controls and conferred twofold increase DLBCL risk.…”

“…This was close to that previously published reports being 50, 54, 47.19, and 50 % respectively (Al Dayel et al 2008;Sarmanova et al 2001;Kerridge et al 2002;Chiu et al 2005;Gra et al 2008). Statistical analysis revealed that para-aortic lymphadenopathy was more prominent among DLBCL patients with normal GSTM1 alleles.…”

“…This is in accordance with the studies of Kerridge et al (2002) and Al Dayel et al (2008). On the contrary, previous studies reported that there were no apparent association between the GSTT1 null genotype and NHL risk (Gra et al 2008, Sarmanova et al 2001Chiu et al 2005;Soucek et al 2002).…”

“…In Saudi Arabian patients, the frequency of GSTT1 null genotype was higher as reported by Al Dayel et al (2008) being 79.7 %, while it was lower in previous studies done on Norwegian, Australian, American, and Russian patients being 17.1 %, 34, 17.9, and 26.5 % respectively (Sarmanova et al 2001;Kerridge et al 2002;Chiu et al 2005;Gra et al 2002;Soucek et al 2002). This could be attributed to racial diVerences between the studied groups.…”