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Association between genetic polymorphisms of the cytochromes P-450 (1A1, 2D6, and 2E1) and the susceptibility to pancreatic cancer.

Lee HC, Yoon YB, Kim CY - Korean J. Intern. Med. (1997)

Bottom Line: Metabolic activation is a prerequisite for the carcinogenic effect of many carcinogens, and considerable interindividual variation exists in the metabolic capacity to activate the carcinogens.The frequencies for the mutant c2 allele of the CYP2E1 were 0.19 and 0.30, respectively, but with no statistical significance.Two persons homozygous for a gene deletion of the CYP2D6 were observed among control subjects; other mutations were not observed among either the patients or controls.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Korea.

ABSTRACT

Objectives: Metabolic activation is a prerequisite for the carcinogenic effect of many carcinogens, and considerable interindividual variation exists in the metabolic capacity to activate the carcinogens. The cytochromes P-450 (CYPs) are responsible for the activation mechanism, and polymorphisms of the CYPs (CYP1A1, CYP2D6, and possibly CYP2E1) are known to be related to increased susceptibility to smoking related Kreyberg type I lung cancer. The aim of this study is to clarify the relationship of genetic polymorphisms of the CYPs to susceptibility to pancreatic cancer, another smoking-related cancer.

Methods: We analyzed 45 samples from patients with pancreatic cancer and 53 samples from controls. DNA was isolated from blood samples and the CYP1A1, 2D6 and 2E1 genes were amplified by PCR. Analyzing the genotypes of the CYPs by allele-specific PCR or RFLP analysis, we assessed the allele frequencies for each mutation of the CYPs among the patients with pancreatic cancer and the controls.

Results: The allele frequencies for the mutation in the 3'-flanking region of the CYP1A1 among the cases and the controls were 0.31 and 0.36, respectively. The allele frequencies for the exon 7 mutation of the CYP1A1 were 0.16 and 0.23, respectively, but with no statistical significance. The frequencies for the mutant c2 allele of the CYP2E1 were 0.19 and 0.30, respectively, but with no statistical significance. Two persons homozygous for a gene deletion of the CYP2D6 were observed among control subjects; other mutations were not observed among either the patients or controls.

Conclusion: We could not find any evidence that polymorphisms of the CYPs are associated with increased susceptibility to pancreatic cancer.

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Related in: MedlinePlus

Polymorphisms of the CYP1A1 gene in the 3′-flanking region. The polymorphism was studied by PCR followed by Msp I digestion. The mutant allele has the Msp I site whereas the wild-type allele does not. Lane M, HaeIII-digested Φ×174 DNA molecular weight markers; Lane 1, wild-type homozygote (wt1/wt1); Lane 2, heterozygote (wt1/m1); Lane 3, mutant homozygote (m1/m1).
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f1-kjim-12-2-128-3: Polymorphisms of the CYP1A1 gene in the 3′-flanking region. The polymorphism was studied by PCR followed by Msp I digestion. The mutant allele has the Msp I site whereas the wild-type allele does not. Lane M, HaeIII-digested Φ×174 DNA molecular weight markers; Lane 1, wild-type homozygote (wt1/wt1); Lane 2, heterozygote (wt1/m1); Lane 3, mutant homozygote (m1/m1).

Mentions: The CYP1A1 genotypes ascribed to the mutation at position 6235 in the 3′-flanking region were determined according to the procedure of Kawajiri et al with some modifications7). Primers P79 (5′-AAGAGGTGTAGCCGCTGCACT-3′) and P80 (5′-TAGGAGTCTTGTCTCATGCCT-3′) were used for amplification of the 3′-flanking region of the CYP1A1 gene. Target DNA (about 500ng) was amplified in a 50-μL reaction mixture containing 10mM Tris (pH 8.3), 50mM KCI, 1mM MgCl2, 100 μM of each dNTP, 1 unit Taq DNA polymerase, and 10 pmole of each primer P79 and P80. Thirty-four cycles of amplification were carried out under the following conditions: 30 sec at 94°C for denaturation; 1 min at 65°C ; and 1 min at 72°C for primer annealing and extension. The amplified products of 335 base pairs were digested with Msp I for 8 hours at 37°C, and the products were subjected to electrophoresis in a 2% agarose gel. Absence of the Msp I site in both alleles represents the homozygous wild-type genotype (wt1/wt1) and is characterized by single 335-bp fragment. Persons with mutations (m1) in homozygous state (m1/m1) show 206- and 129-bp fragments. Heterozygotes show 335-, 206-, and 129-bp fragments (Fig. 1).


Association between genetic polymorphisms of the cytochromes P-450 (1A1, 2D6, and 2E1) and the susceptibility to pancreatic cancer.

Lee HC, Yoon YB, Kim CY - Korean J. Intern. Med. (1997)

Polymorphisms of the CYP1A1 gene in the 3′-flanking region. The polymorphism was studied by PCR followed by Msp I digestion. The mutant allele has the Msp I site whereas the wild-type allele does not. Lane M, HaeIII-digested Φ×174 DNA molecular weight markers; Lane 1, wild-type homozygote (wt1/wt1); Lane 2, heterozygote (wt1/m1); Lane 3, mutant homozygote (m1/m1).
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4531995&req=5

f1-kjim-12-2-128-3: Polymorphisms of the CYP1A1 gene in the 3′-flanking region. The polymorphism was studied by PCR followed by Msp I digestion. The mutant allele has the Msp I site whereas the wild-type allele does not. Lane M, HaeIII-digested Φ×174 DNA molecular weight markers; Lane 1, wild-type homozygote (wt1/wt1); Lane 2, heterozygote (wt1/m1); Lane 3, mutant homozygote (m1/m1).
Mentions: The CYP1A1 genotypes ascribed to the mutation at position 6235 in the 3′-flanking region were determined according to the procedure of Kawajiri et al with some modifications7). Primers P79 (5′-AAGAGGTGTAGCCGCTGCACT-3′) and P80 (5′-TAGGAGTCTTGTCTCATGCCT-3′) were used for amplification of the 3′-flanking region of the CYP1A1 gene. Target DNA (about 500ng) was amplified in a 50-μL reaction mixture containing 10mM Tris (pH 8.3), 50mM KCI, 1mM MgCl2, 100 μM of each dNTP, 1 unit Taq DNA polymerase, and 10 pmole of each primer P79 and P80. Thirty-four cycles of amplification were carried out under the following conditions: 30 sec at 94°C for denaturation; 1 min at 65°C ; and 1 min at 72°C for primer annealing and extension. The amplified products of 335 base pairs were digested with Msp I for 8 hours at 37°C, and the products were subjected to electrophoresis in a 2% agarose gel. Absence of the Msp I site in both alleles represents the homozygous wild-type genotype (wt1/wt1) and is characterized by single 335-bp fragment. Persons with mutations (m1) in homozygous state (m1/m1) show 206- and 129-bp fragments. Heterozygotes show 335-, 206-, and 129-bp fragments (Fig. 1).

Bottom Line: Metabolic activation is a prerequisite for the carcinogenic effect of many carcinogens, and considerable interindividual variation exists in the metabolic capacity to activate the carcinogens.The frequencies for the mutant c2 allele of the CYP2E1 were 0.19 and 0.30, respectively, but with no statistical significance.Two persons homozygous for a gene deletion of the CYP2D6 were observed among control subjects; other mutations were not observed among either the patients or controls.

View Article: PubMed Central - PubMed

Affiliation: Department of Internal Medicine, Seoul National University College of Medicine, Korea.

ABSTRACT

Objectives: Metabolic activation is a prerequisite for the carcinogenic effect of many carcinogens, and considerable interindividual variation exists in the metabolic capacity to activate the carcinogens. The cytochromes P-450 (CYPs) are responsible for the activation mechanism, and polymorphisms of the CYPs (CYP1A1, CYP2D6, and possibly CYP2E1) are known to be related to increased susceptibility to smoking related Kreyberg type I lung cancer. The aim of this study is to clarify the relationship of genetic polymorphisms of the CYPs to susceptibility to pancreatic cancer, another smoking-related cancer.

Methods: We analyzed 45 samples from patients with pancreatic cancer and 53 samples from controls. DNA was isolated from blood samples and the CYP1A1, 2D6 and 2E1 genes were amplified by PCR. Analyzing the genotypes of the CYPs by allele-specific PCR or RFLP analysis, we assessed the allele frequencies for each mutation of the CYPs among the patients with pancreatic cancer and the controls.

Results: The allele frequencies for the mutation in the 3'-flanking region of the CYP1A1 among the cases and the controls were 0.31 and 0.36, respectively. The allele frequencies for the exon 7 mutation of the CYP1A1 were 0.16 and 0.23, respectively, but with no statistical significance. The frequencies for the mutant c2 allele of the CYP2E1 were 0.19 and 0.30, respectively, but with no statistical significance. Two persons homozygous for a gene deletion of the CYP2D6 were observed among control subjects; other mutations were not observed among either the patients or controls.

Conclusion: We could not find any evidence that polymorphisms of the CYPs are associated with increased susceptibility to pancreatic cancer.

Show MeSH
Related in: MedlinePlus