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Interaction among Carcinogen‐biotransformation Genes (N‐acetyltransferase 1 and 2) and Prostate Cancer Risk Using a Comprehensive Analytical Approach
Author(s) -
Templeton Tiva M,
Thacker Brandon,
Srivastava Daya,
Komolafe Oyeyemi,
Pihur Vasyl,
Brock Guy,
Doll Mark,
Hein David,
Kidd La Creis
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-a
Subject(s) - prostate cancer , multifactor dimensionality reduction , carcinogen , cancer , gene , logistic regression , allele , biology , genetics , n acetyltransferase , oncology , medicine , genotype , single nucleotide polymorphism , acetylation
Prostate cancer (PCA) incidence and mortality are highest among African‐American (AA) men. Its detection and disparities could be improved through the identification of genetic susceptibilities within essential biological pathways. Interactions among highly variant N ‐acetyltransferase (NAT) genes, central to carcinogen‐biotransformation pathways, modulate susceptibility to environmentally induced cancers, as demonstrated in previous reports. This study evaluates the interplay between two highly variant biotransformation genes (i.e., NAT1 and NAT2 ) and their influence on prostate cancer risk within a large and unique PCA case‐control study of 918 AA men. The intricate interaction between polymorphic NAT1 and NAT2 was analyzed using conventional logistic regression analysis (LR) complemented with multiple dimensionality reduction. We hypothesize individuals who inherit two or more high‐risk NAT alleles (e.g., NAT1*10 and slow NAT2*5 ) will have an increased risk of developing prostate cancer. Despite the relatively high prevalence (68.6–87.1%) of the high‐risk NAT1*10 and slow NAT2 alleles among our study participants, their interaction did not significantly modify prostate cancer risk (P = 0.099). Future studies will evaluate the complex interplay among variant biotransformation and DNA repair genes and their joint modifying effects on prostate cancer risk. NCI 3RO1 CA034627 ‐19S