SHORT COMMUNICATION: Influence of a mutation reducing the catalytic activity of the cytochrome P450 CYP2D6 on lung cancer susceptibility

Legrand, M.; Stücker, L.; Marez, Delphine; Sabbagh, N; Lo-Guidice, Jean-Marc; Broly, Franck

doi:10.1093/carcin/17.10.2267

Cited by 14 publications

(6 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In the case of CYP2A6 and CYP2D6, the altered base causes a reduction in enzyme function (22,23). On the contrary, the variant form of the protein causes the enhanced activity of CYP1A1 and CYP1B1 enzymes (24,25).…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms of Catechol-O-Methyltransferase in Men with Renal Cell Cancer

Tanaka

Hirata

Chen

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

The estrogen metabolite, 4-hydroxy-estrogen, has been shown to play a role in malignant transformation of male kidneys. To counteract the effects of this catechol-estrogen, the catechol-O-methyltransferase (COMT) enzyme is capable of neutralizing the genotoxic effects of this compound. A polymorphic variant of COMT has been shown to have a reduced enzyme activity, and thus, we hypothesize that single nucleotide polymorphisms of the COMT gene can be a risk factor for renal cell cancer (RCC). To determine this hypothesis, a study of a Japanese male population was used and the genetic distributions of COMT polymorphisms at codons 62 (C!T), 72 (G!T), and 158 (G!A) were analyzed in 157 normal healthy subjects and 123 sporadic RCC (clear cell type) samples by using a sequence-specific PCR technique. These experiments show that the variant genotype (P = 0.025) and allele (P = 0.011) at codon 62 is a risk factor for RCC. The odds ratio and 95% confidence interval for cancer were 3.16 and 1.29 to 7.73, respectively, for the T/T genotype as compared with wild-type. No associations for renal cancer were found at either codons 72 or 158 in this Japanese male population. However, codons 62 and 158 were observed to be in linkage disequilibrium, and haplotype analysis shows the combined forms of T-A, T-G, and C-A to be associated with RCC as compared with C-G (P < 0.001). When evaluating the risk of COMT polymorphisms with grade of cancer, no associations were observed for any of the genotypes. This study is the first to report COMT polymorphism to be associated with RCC. These results are important in understanding the role of COMT polymorphisms in the pathogenesis of RCC.

show abstract

Section: Introductionmentioning

confidence: 99%

Polymorphisms of Catechol-O-Methyltransferase in Men with Renal Cell Cancer

Tanaka

Hirata

Chen

et al. 2007

Cancer Epidemiology, Biomarkers &Amp; Prevention

View full text Add to dashboard Cite

show abstract

“…Polymorphisms and mutations in genes cause changes in the function of proteins, which can reduce [27][28][29] or enhance [30][31][32] the activation of enzymes. Polymorphisms of various genes have also been shown to be associated with cancers [33][34][35].…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms of estrogen receptor alpha in prostate cancer

Tanaka¹,

Sasaki²,

Kaneuchi³

et al. 2003

Molecular Carcinogenesis

View full text Add to dashboard Cite

Estrogen receptor (ER) alpha polymorphisms have been shown to be involved in the oncogenesis of several organs. We hypothesize that polymorphisms of the ERalpha gene are risk factors for prostate cancer. The genotypic distributions of six different loci (codons: 10 T-->C, 87 G-->C, 243 C-->T, 325 C-->G, 594 G-->A, and intron 1 C-->T) of the ERalpha gene were analyzed in prostate cancer tissues. The DNA from 115 cases of prostate cancer (Japanese population) was analyzed by sequence-specific polymerase chain reaction (PCR) and direct sequencing to determine the genotypic and allelic frequencies of the six different polymorphic loci of ERalpha. The relative risk of variant genotype was calculated by comparison with 200 healthy controls. Results of this study showed that the frequency of the variant genotype (C/C) on codon 10 was significantly higher in prostate cancer patients. The odds ratio (OR) was calculated as 3.26 compared to wild-type (T/T) with a 95% confidence interval (CI) of 1.58-6.73. Allele frequency at codon 10 also differed between groups. No association was found between codon 10 polymorphism and the stage of cancer. Polymorphism was not observed in codon 87, and frequencies of genotypes and alleles at other loci (intron 1, codons 243, 325, and 594) were not statistically different between cancer and controls. The present study suggests that polymorphism in codon 10 of ERalpha may be a risk factor for prostate cancer. These results are important in understanding the role of ERalpha polymorphism in the pathogenesis of prostate cancer.

show abstract

“…Although the first association between CYP2D6 enzyme activity and lung cancer risk was described in 1984, the role of CYP2D6 in lung cancer risk is still a controversial topic (Ayesh, Idle, Ritchie, Crothers, & Hetzel, 1984). Although most studies failed to identify a significant association, some studies reported a minor positive association (Agundez et al, 2001;Legrand et al, 1996;London et al, 1997). The overall results indicated a modest association of CYP2D6 polymorphism with lung cancer risk.…”

Section: Cyp2d Subfamilymentioning

confidence: 99%