Xenobiotic/drug metabolizing enzyme and TP53 polymorphisms and clinical outcome in advanced nonsmall cell lung cancer patients

Abstract

Background/aim: The association between polymorphisms of xenobiotic/drug metabolizing enzymes and TP53 and response to chemotherapy and survival of patients with nonsmall cell lung cancer (NSCLC) are limited and inconclusive. In this study, CYP2E1*5B, CYP2E1*6, CYP2E1*7B, GSTO1 (A140D), and TP53 (Arg72Pro) polymorphisms and response to platinum-based chemotherapy and survival in 137 advanced stage NSCLC patients were investigated.Materials and methods: Genetic polymorphism analyses were determined by polymerase chain reaction (PCR) coupled with restriction fragment length polymorphism (RFLP). Results:The patients with TP53 Pro/Pro variant were more likely to be resistant to chemotherapy than those with Arg/Arg variants with marginal significance (P = 0.066). We also analyzed these gene variants in combination with CYP1A1 (Ile462Val), CYP1B1 (Asn453Ser), GSTM1, GSTP1 exon 5 (Ile105Val), and GSTP1 exon 6 (Ala114Val) and GSTT1 polymorphic genes that we have previously genotyped in the same patients (Ada et al., Neoplasma, 57, 512-527, 2010). The multivariate analysis revealed that adjusted hazard ratio (HR) of death of the combined variant genotypes of TP53 (Arg72Pro, Pro72Pro) and CYP1A1 (Ile462Val, Val462Val) increased significantly as compared to wild-type genotypes (HR,

Cytochrome P-450 Polymorphisms and Clinical Outcome in Patients with Non-Small Cell Lung Cancer

“…Moreover, almost no information is available with 18 who observed no significant association between the CYP2E1*5B polymorphism and response to chemotherapy in NSCLC. Likewise, the recent results of Karacaoğlan et al 9 on the CYP2E1*5B polymorphism are also in line with the findings of Li et al 18 , both in regard to response to chemotherapy and survival. However, their findings are in contrast to those of Oyama et al 24 and Haque et al 25 in respect to survival.…”

“…However, their findings are in contrast to those of Oyama et al 24 and Haque et al 25 in respect to survival. The findings of Karacaoğlan et al 9 in regard to the effect of CYP2E1*6 polymorphism on survival also coincided with the results of Przygodzki et al 23 The only study for the CYP2E1*7B polymorphism on this issue was reported by Karacaoğlan et al 9 who observed no association between the CYP2E1*7B polymorphism and response to chemotherapy and survival in patients with NSCLC.…”

“…18 The study of Ada et al 7 in NSCLC patients also revealed that the combined CYP1A1*2C and GSTP1 (Ile105Val) mutant alleles or CYP1B1*4 and GSTP1 (Ile105Val) mutant alleles had notable trends toward worsening of survival. Recently, Karacaoğlan et al 9 demonstrated that combined CYP1A1*2C and TP53 (Arg72Pro) mutant genotypes were associated with the worsening of the survival in NSCLC patients. In addition, they observed that the combined CYP2E1*7B and TP53 (Arg72Pro) mutant alleles had notable trends toward worsening survival.…”

“…5 There is accumulating evidence to support the hypothesis that genetic polymorphisms alter drug response and survival. [6][7][8][9][10][11] Cytochrome P450 (CYP) is a superfamily of phase I oxidation enzymes, the first 3 families of which metabolize xenobiotics such as environmental carcinogens and various drugs (Table 1) including antineoplastic drugs (Table 2). [12][13][14][15][16] They are also involved in drug resistance.…”

Glutathione S‑transferase ω 1 promotes the proliferation, migration and invasion, and inhibits the apoptosis of non‑small cell lung cancer cells, via the JAK/STAT3 signaling pathway

“…For example, a previous study revealed that polymorphisms in GSTO1 increased the risk of hepatocellular carcinoma (9). In addition, accumulating evidence has reported the relationship between GSTO1 gene polymorphisms and NSCLC (10)(11)(12). For instance, Bulus et al (13) demonstrated that GSTO1 expression levels in colon cancer cells were significantly upregulated compared with in normal colon epithelial cells.…”