Premium
Combined Effects of Variant N‐Acetyltranserase 1 (NAT1) and Multiple Drug Resistance 1 (MDR1) Genes in Prostate Cancer Risk
Author(s) -
Komolafe Oyeyemi O,
Srivastava Daya S,
Thacker Brandon,
Templeton Tiva,
Doll Mark,
Hein David,
Pihur Vasyl,
Brock Guy,
Kidd LaCreis R
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.5.a416
Subject(s) - multifactor dimensionality reduction , prostate cancer , carcinogenesis , allele , genotype , logistic regression , biology , gene , genetics , oncology , computational biology , bioinformatics , cancer , medicine , single nucleotide polymorphism
Prostate cancer (PCA) detection could be improved by identifying genetic susceptibility markers within essential biological pathways. The goal of this study is to identify an important panel of genetic susceptibility markers. This study evaluates the interaction between two variant genes (NAT1 and MDR1) in relation to PCA risk using a case‐control study of 918 African American men. Individuals who have at least one rapid activation NAT1*10 combined with one or more MDR1 3435T alleles (linked with reduced xenobiotic‐cellular extrusion) were hypothesized to have an elevated risk of PCA relative to those with low risk genotypes. Genetic alterations detected in germ‐line DNA collected from 220 incident PCA cases and 698 healthy age matched controls were assessed using TaqMan real‐time polymerase chain reaction. For the first time to our knowledge, the complex interaction among highly variant pharmacokinetic genes and their combined modifying effects on PCA risk were evaluated using a computationally savvy methodology that compliments logistic regression models with multifactor dimensionality reduction. The high‐risk NAT1*10 combined with high risk MDR1 alleles did not modify PCA risk (OR = 1.07;95%CI = 0.53–2.14, P=0.58). Future studies will expand our current efforts by considering other biological pathways important in PCA tumorigenesis using advanced biostatistical tools. Bales Medical Research Fund