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Verfasst von:Dally, Heike [VerfasserIn]   i
 Edler, Lutz [VerfasserIn]   i
 Jäger, Birgit [VerfasserIn]   i
 Schmezer, Peter [VerfasserIn]   i
 Spiegelhalder, Bertold [VerfasserIn]   i
 Dienemann, Hendrik [VerfasserIn]   i
 Drings, Peter [VerfasserIn]   i
 Schulz, Volker [VerfasserIn]   i
 Kayser, Klaus [VerfasserIn]   i
 Bartsch, Helmut [VerfasserIn]   i
 Risch, Angela [VerfasserIn]   i
Titel:The CYP3A4*1B allele increases risk for small cell lung cancer
Titelzusatz:effect of gender and smoking dose
Verf.angabe:Heike Dally, Lutz Edler, Birgit Jäger, Peter Schmezer, Bertold Spiegelhalder, Hendrik Dienemann, Peter Drings, Volker Schulz, Klaus Kayser, Helmut Bartsch and Angela Risch
Jahr:2003
Umfang:12 S.
Fussnoten:Im Titel ist [ast] als Sternchen dargestellt ; Gesehen am 14.12.2020
Titel Quelle:Enthalten in: Pharmacogenetics and genomics
Ort Quelle:Philadelphia, Pa. : Lippincott Williams & Wilkins, 1991
Jahr Quelle:2003
Band/Heft Quelle:13(2003), 10, Seite 607-618
ISSN Quelle:1744-6880
Abstract:CYP3A isozymes are involved in tobacco carcinogen- and steroid-metabolism, and are expressed in human lung tissue showing interindividual variation in expression and activity. The CYP3A4*1B allele has been associated with a two-fold higher promoter activity and with high-grade prostate cancers. The very frequent intron 3 polymorphism in the CYP3A5 gene (CYP3A5*3) results in decreased CYP3A5 protein levels. A case-control study was conducted in 801 Caucasian lung cancer patients that included 330 adenocarcinomas, 260 squamous cell carcinomas, 171 small cell lung cancers (SCLC) and 432 Caucasian hospital-based controls. CYP3A-genotyping was performed by capillary polymerase chain reaction followed by fluorescence-based melting curve analysis. A significantly increased SCLC risk for CYP3A4*1B allele carriers [odds ratio (OR) 2.25, 95% confidence interval (CI) 1.11-4.55, P = 0.02] was found. After dividing cases and controls by gender, an increased lung cancer risk for CYP3A4*1B carriers (OR 3.04, 95% CI 0.94-9.90, P = 0.06) for women but not for men (OR 1.00, 95% CI 0.56-1.81) was revealed. Heavier smoking men (≥ 20 pack-years) with the CYP3A4*1B allele had a significant OR for lung cancer of 3.42 (95% CI 1.65-7.14, P = 0.001) compared to *1A/*1A carriers with lower tobacco exposure (< 20 pack-years). For women, the respective OR was 8.00 (95% CI 2.12-30.30, P = 0.005). Genotype frequencies were generally in Hardy-Weinberg equilibrium, except for CYP3A5 where a greater than expected number of CYP3A5*1 homozygotes was observed among cases (P = 0.006). In addition, we observed linkage disequilibrium of CYP3A4 and CYP3A5 (P< 0.00001), but a non-significantly increased lung cancer risk was only found for homozygous CYP3A5*1 allele carriers (OR 5.24, 95% CI 0.85-102.28, P = 0.14) but not for heterozygotes. To confirm our observation that the CYP3A4*1B allele increases SCLC risk and modifies the smoking-related lung cancer risk in a gender-specific manner, further studies, including CYP3A haplotype analysis, will be necessary.
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Volltext: https://journals.lww.com/jpharmacogenetics/Fulltext/2003/10000/The_CYP3A4_1B_allele_increases_risk_for_small_cell.4.aspx
Datenträger:Online-Ressource
Sprache:eng
K10plus-PPN:174272292X
Verknüpfungen:→ Zeitschrift

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