CYP1A1 (Ile⁴⁶²Val), CYP1B1 (Ala¹¹⁹Ser and Val⁴³²Leu), GSTM1 (null), and GSTT1 (null) Polymorphisms and Bladder Cancer Risk in a Turkish Population

Abstract

We aimed to investigate bladder cancer risk with reference to polymorphic variants of cytochrome p450 (CYP) 1A1, CYP1B1, glutathione S-transferase (GST) M1, and GSTT1 genes in a case control study. Polymorphisms were examined in 114 bladder cancer patients and 114 age and sex-matched cancer-free subjects. Genotypes were determined using allele specific PCR for CYP1A1 and CYP1B1 genes, and by multiplex PCR and melting curve analysis for GSTM1 and GSTT1 genes. Our results revealed a statistically significant increased bladder cancer risk for GSTT1 null genotype carriers with an odds ratio of 3.06 (95% confidence interval=1.39-6.74, p=0.006). Differences of CYP1A1, CYP1B1 and GSTM1 genotype frequencies were not statistically significant between patients and controls. However, the specific combination of GSTM1 null, GSTT1 null, and CYP1B1 codon 119 risk allele carriers and specific combination of GSTM1 present, GSTT1 null, and CYP1B1 432 risk allele carriers exhibited increased cancer risk in the combined analysis. We did not observe any association between different genotype groups and prognostic tumor characteristics of bladder cancer. Our results indicate that inherited absence of GSTT1 gene may be associated with bladder cancer susceptibility, and specific combinations of GSTM1, GSTT1 and CYP1B1 gene polymorphisms may modify bladder cancer risk in the Turkish population, without any association being observed for CYP1A1 gene polymorphism and bladder cancer risk.

Lack of Association Between CYP1A1 Polymorphisms and Risk of Bladder Cancer: a Meta-analysis

“…CYP1A1*2B A/G (I1e462Val) and Bladder Cancer Risk: As established above, six studies, with a total of 908 cases and 815 controls, evaluated the association of BC risk in I1e462Val A/G mutation Fontana et al, 2009;Grando et al, 2009;Ozturk et al, 2011;Berber et al, 2013;Fu et al, 2013). According to our results, no significant association between this polymorphism and BC risk was found in all genetic models in the overall populations: i) G vs. A (OR = 1.04, 95% CI = 0.74-1.47, P = 0.810); ii) GG vs. AA (OR = 1.47, 95% CI = 0.70-3.07, P = 0.308); iii) AG vs. AA (OR = 0.97, 95% CI = 0.74-1.27, P = 0.819); iv) GG+AG vs. AA (OR = 1.01, 95% CI = 0.68-1.48, P = 0.970); v) GG vs. AG+AA (OR = 1.45, 95% CI = 0.70-3.02, P = 0.317).…”

“…Manual search of the reference lists did not reveal any additional eligible studies. Thus, eight relevant studies focused on two of the most studied polymorphisms in CYP1A1 (CYP1A1*2B A/G (I1e462Val) and CYP1A1*2A T/C (MspI) and risk of BC were included in our meta-analysis Li et al, 2007;Srivastava et al, 2008;Grando et al, 2009;Fontana et al, 2009;Ozturk et al, 2011;Fu et al, 2013;Berber et al, 2013). Of these, the study by Brockmöller et al identified the relationship between CYP1A1 polymorphisms and BC risk in both alleles, and were therefore treated independently.…”

Clinical, Cytogenetic and CYP1A1 exon-1 Gene Mutation Analysis of Beedi Workers in Vellore Region, Tamil Nadu

“…is one of the major environmental risk factors for breast cancer due to the presence of procarcinogens in tobacco (Berber et al, 2013). In our study most of the workers rolling beedi for more than 10 years and they affected with different types of health issues like headache, back pain, urinary infection, leg pain, shoulder pain, low eye contact, blood pressure, skin allergy.…”

Are Bladder Neoplasms More Aggresive in Patients with a Smoking-related Second Malignancy?

“…From the molecular point of view, evidence in the literature supports the existence of distinct pathogenetic pathways involved in bladder cancer development (Berber et al, 2013). By departing from this fact, we have proposed the hypothesis that the prognosis of bladder cancer may be worse in the presence of cancers associated with smoking and pathological stage especially if the histological grade is high.…”