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Epidemiology

Homozygous Rapid Arylamine N-Acetyltransferase (NAT2) Genotype as a Susceptibility Factor for Lung Cancer

Ingolf Cascorbi, Jürgen Brockmöller, Przemyslaw M. Mrozikiewiz, Steffen Bauer, Robert Loddenkemper and Ivar Roots
Ingolf Cascorbi
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Jürgen Brockmöller
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Przemyslaw M. Mrozikiewiz
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Steffen Bauer
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Robert Loddenkemper
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Ivar Roots
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DOI:  Published September 1996
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Abstract

The polymorphic arylamine N-acetyltransferase (NAT2) is supposed to be a susceptibility factor for certain malignancies. A phenotyping study in 389 lung cancer patients revealed a similar distribution of rapid and slow acetylators by the caffeine test to that in 657 reference subjects (odds ratio, 1.05; 95% confidence limits, 0.81, 1.36; not significant). A separate group of 155 lung cancer patients was studied by genotyping NAT2 and was compared with a matched reference group of 310 unrelated patients and with 278 healthy volunteers. The NAT2 genotype was characterized by PCR-RFLP at nucleotide positions 191, 282, 341, 481, 590, 803, and 857. For evaluation of nucleotide 341, a 3′-mismatch primer was used. Homozygous wild-type genotypes NAT2*4/*4 were confirmed by DNA sequencing. Genotypes for rapid acetylation amounted to 43.9% among lung cancer and 41.6% among reference patients (odds ratio, 1.10 95% confidence limits, 0.73, 1.65; not significant). Discrimination into homozygous and heterozygous carriers of allele NAT2*4 revealed a distinct overrepresentation of NAT2*4/*4 genotypes amid lung cancer patients (odds ratio, 2.36; 95% confidence limits, 1.05, 5.32; P = 0.018). Logistic regression analysis considering sex, age, and smoking provided an odds ratio of 3.04 (95% confidence limits, 1.37, 6.75; P = 0.003). Hence, carriers of the NAT2*4/*4 genotype, with its especially high acetylation capacity, are at significantly increased risk to lung cancer.

Footnotes

  • ↵1 This work was partly supported by a grant of the German Federal Ministry of Education, Science, Research and Technology (grant no. 01 EC 9408/0).

  • ↵2 To whom requests for reprints should be addressed. Phone: 49-30-2802-3635; Fax: 49-30-2802-5153; E-mail: cascorbi@rz.charite.hu-berlin.de.

  • Received February 14, 1996.
  • Accepted July 2, 1996.
  • ©1996 American Association for Cancer Research.
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September 1996
Volume 56, Issue 17
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Homozygous Rapid Arylamine N-Acetyltransferase (NAT2) Genotype as a Susceptibility Factor for Lung Cancer
Ingolf Cascorbi, Jürgen Brockmöller, Przemyslaw M. Mrozikiewiz, Steffen Bauer, Robert Loddenkemper and Ivar Roots
Cancer Res September 1 1996 (56) (17) 3961-3966;

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Homozygous Rapid Arylamine N-Acetyltransferase (NAT2) Genotype as a Susceptibility Factor for Lung Cancer
Ingolf Cascorbi, Jürgen Brockmöller, Przemyslaw M. Mrozikiewiz, Steffen Bauer, Robert Loddenkemper and Ivar Roots
Cancer Res September 1 1996 (56) (17) 3961-3966;
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