Cytochrome P450 CYP2D6 gene polymorphism and lung cancer susceptibility in Caucasians

Legrand-Andréoletti, M; Stücker, Isabelle; Marez, Delphine; Galais, P; Cosme, José; Sabbagh, N; Spire, Catherine; Cénée, Sylvie; Jj, Lafitte; Beaune, P; Broly, Franck

doi:10.1097/00008571-199802000-00002

Cited by 18 publications

(11 citation statements)

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“…DNA samples were stored at −20 ° C. The DNA concentration was determined by optical density at 260 nm. All samples (except 4) were previously genotyped for CYP2D6 alleles [12] (Table 1). However for these DNA samples, Southern blotting analysis and long PCR were available.…”

Section: Methodsmentioning

confidence: 99%

Determination of Cytochrome P450 2D6 (CYP2D6) Gene Copy Number by Real‐Time Quantitative PCR

Bodin

Beaune

Loriot

2000

BioMed Research International

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Gene dosage by real-time quantitative PCR has proved to be accurate for measuring gene copy number. The aim of this study was to apply this approach to the CYP2D6 gene to allow for rapid identification of poor and ultrarapid metabolizers (0, 1, or more than 2 gene copy number). Using the 2−ΔΔCt calculation method and a duplex reaction, the number of CYP2D6 gene copies was determined. Quantitative PCR was performed on 43 samples previously analyzed by Southern blotting and long PCR including 20 samples with a heterozygous deletion, 11 with normal copy number (2 copies), and 12 samples with duplicated genes. The average ratio ranged from 1.02 to 1.28, 1.85 to 2.21, and 2.55 to 3.30, respectively, for the samples with 1 copy, 2 copies, and 3 copies. This study shows that this method is sensitive enough to detect either a heterozygous gene deletion or duplication.

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Section: Methodsmentioning

confidence: 99%

Determination of Cytochrome P450 2D6 (CYP2D6) Gene Copy Number by Real‐Time Quantitative PCR

Bodin

Beaune

Loriot

2000

BioMed Research International

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“…CYP2D6 genetic polymorphism was performed. In two studies upon Caucasians, the mutant CYP2D6 allele was shown to be associated with increased lung cancer risk [60,61]. It was shown that over 20% of lung and larynx cancer Caucasian patients show genetic mutation of CYP2D6 gene leading to extensive or ultrarapid debrisoquine metabolism [55].…”

Section: Cyp2 Gene Familymentioning

confidence: 99%

Polymorphism of selected enzymes involved in detoxification and biotransformation in relation to lung cancer

2007

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“…The homozygous CYP2D6*4/CYP2D6*4 genotype can be a factor of an increased risk of the development of laryngeal carci noma (Gajeckaa et al, 2005). Studies on the associa tion between polymorphisms in the CYP2D6 gene and the development of lung cancer did not provide defin itive results (London et al, 1997;Legrand Andreoletti et al, 1998;Shaw et al, 1998;Au et al, 2001).…”

Section: Introductionmentioning

confidence: 99%

Polymorphisms of the GSTM1, GSTT1, and CYP2D6 xenobiotic biotransformation genes, which are possible risk markers of cancer in populations of indigenous ethnic groups and Russians of North Siberia

Korchagina

Osipova

Vavilova

et al. 2012

Russ J Genet Appl Res

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The CYP2D6, GSTM1, and GSTT1 xenobiotic biotransformation genes are involved in processes of carcinogenesis in humans due to the presence of mutant variants that decrease or block the expression of genes. Since the middle of the 20th century, there has been an extensive increase in cancer morbidity in human populations, including indigenous ethnic groups of Siberia. The problem of ethnic differences in sus ceptibility to cancer is still pressing. The study of polymorphisms of the CYP2D6 (CYP2D6*3 and CYP2D6*4 alleles), GSTM1, and GSTT1 (GSTM1 0/0 and GSTT1 0/0 "null" genotypes) genes (which are considered as genetic markers of the risk of cancer) was conducted for the first time in practically healthy representatives of the Samoyedic ethnic groups (Selkups, Forest Nenets, and Nganasans) and Russians from Siberia. A signif icant variability in the CYP2D6*4 and GSTM1 0/0 frequency distribution in northern populations was detected. At the same time, there are no significant differences in frequencies of the CYP2D6*3 and GSTT1 0/0 variants among indigenous populations of the Selkups, Forest Nenets, and Nganasans. In the CYP2D6*4 allele frequencies, indigenous ethnic groups are intermediate between Russians of Siberia and Mongolians of China. However, frequencies of the null GSTM1 0/0 and GSTT1 0/0 genotypes in indigenous ethnic groups are significantly lower than in populations of Russians of Siberia and Mongoloids of China (p < 0.05). Gen erally, according to all four studied polymorphic variants, it is possible to predict a decreased risk of cancer in indigenous Samoyedic ethnic groups, as compared with Russians of Siberia. The Forest Nenets population, with an increased frequency of the GSTM1 0/0 genotypes, is an exception; this can be caused by the original ity of their marriage structure and increased inbreeding coefficient. The results we obtained can also be important in predicting the probability of complications and a positive response to drugs that are metabolized by the GSTM1, GSTT1, and CYP2D6 enzymes.

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Cytochrome P450 CYP2D6 gene polymorphism and lung cancer susceptibility in Caucasians

Cited by 18 publications

References 0 publications

Determination of Cytochrome P450 2D6 (CYP2D6) Gene Copy Number by Real‐Time Quantitative PCR

Determination of Cytochrome P450 2D6 (CYP2D6) Gene Copy Number by Real‐Time Quantitative PCR

Polymorphism of selected enzymes involved in detoxification and biotransformation in relation to lung cancer

Polymorphisms of the GSTM1, GSTT1, and CYP2D6 xenobiotic biotransformation genes, which are possible risk markers of cancer in populations of indigenous ethnic groups and Russians of North Siberia

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