Debrisoquin oxidation genotype and susceptibility to lung cancer

Abstract

The association between the polymorphism of the cytochrome P450 debrisoquin hydroxylase (CYP2D6) and lung cancer is controversial. Previous reports suggested a link between CYP2D6 phenotype and lung cancer, with poor metabolizers having reduced susceptibility. Nevertheless, negative findings have also been published. By using allele-specific amplification, we have studied the frequency of four CYP2D6 (wild type and mutant) alleles in 89 patients with histologically proved bronchogenic carcinoma and in 98 healthy volunteers. Our findings confirm that poor metabolizers are underpresented among patients with lung cancer because of a different genetic background. Our findings also reveal that the rare CYP2D6(C) mutant allele is sixfold more frequent among patients with lung cancer (p < 0.0005). This suggests that the CYP2D6(C) allele could be considered as an additional risk factor because carriers could have higher susceptibility to the development of lung cancer.

CYP2D6 Polymorphisms in Patients with Porphyrias

“…EM would be more exposed than EIM and PM to genotoxic porphyrinogenic xenobiotic metabolites. Several authors have presented similar results in different studies performed with lung cancer and urinary bladder cancer patients (22)(23)(24). Agündez et al (25) observed a significant correlation between EM and the risk of liver cancer development.…”

Functionally Active Duplications of the <i>CYP2D6</i> Gene Are More Prevalent among Larynx and Lung Cancer Patients

“…CYP2D6*9 alleles, which were present at an increased frequency among lung cancer patients in a previous study from our group [13], were also more frequent among the newly analyzed 31 lung cancer patients. Global frequencies were: lung adenocarcinoma (15%), small-cell lung cancer (8%), and epidermoid lung cancer (13%).…”

“…There were 96 patients with larynx cancer and 103 patients with lung cancer. Seventy-two lung cancer patients have been studied for point mutations in the CYP2D6 gene in a previous study [13]and for gene deletion and duplication in the present study. All patients were evaluated by consultant physicians, and the diagnosis was based on histological analyses.…”

“…Over 95% of the healthy subjects requested agreed to participate in the study. Since gender, age or smoking habits are not related to the CYP2D6 genotype [5, 13], the controls were not fully matched with patients. Blood samples were immediately frozen after collection and kept at –80°C until analyzed.…”

Genetic Variants of CYP2D6 Gene and Cancer Risk: A HuGE Systematic Review and Meta-analysis

“…According to the inclusion criteria, 43 studies (Agúndez et al, 1994;Wundrack et al, 1994;Agúndez et al, 1996;Ladona et al1996;Legrand et al, 1996;London et al, 1997;Agúndez et al, 1998;Febbo et al, 1998; González et al, 1998; Hu et Shaw et al, 1998;Krajinovic et al, 1999;Lemos et al, 1999;Topić et al, 2000;Butler et al, 2001;Liu et al, 2002;Sobti et al, 2003;Chen et al, 2004;Fukatsu et al, 2004;Li et al, 2004;Gajecka et al, 2005;Gomes et al, 2005;Guo et al, 2005;Liang et al, 2005;Mochizuki et al, 2005;Sobti et al, 2005;Aydin-Sayitoglu et al, 2006;Bonanni et al, 2006;Li et al, 2006;Lemos et al, 2007;Chen et al, 2008;Khedhaier et al, 2008;Majumdar et al, 2008;Ouerhani et al, 2008 ;Torresan et al, 2008;Yan et al, 2008;Altayli et al, 2009;Gutman et al, 2009;Lim et al, 2011;Luo et al, 2011;Zhou et al, 2011) appeared to have met the inclusion criteria and were subjected to further examination. The flow chart of study selection is shown...…”