N-acetyltransferase (NAT) 2 acetylator status and age of onset in patients with hereditary nonpolyposis colorectal cancer (HNPCC)

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• 作者：Steffen Pistorius ; Heike Gö ; rgens ; Stefan Krü ; ger ; Christoph Engel ; Elisabeth Mangold ; Constanze Pagenstecher ; Elke Holinski-Feder ; Gabriela Moeslein ; Magnus von Knebel Doeberitz ; Josef Rü
• 关键词：NAT2 ; Modifying genes ; Colorectal cancer ; HNPCC
• 刊名：Cancer Letters
• 出版年：2006
• 出版时间：8 September 2006
• 年：2006
• 卷：241
• 期：1
• 页码：150-157
• 全文大小：182 K

文摘

N-acetyltransferase (NAT) 2 is an essential polymorphic enzyme involved in the metabolism of various xenobiotics, including potential carcinogens. The individual differences in the NAT2 metabolic capacity are caused by allelic variants of the NAT2 gene which are determined by a pattern of single nucleotide polymorphisms (SNPs) resulting in slow (SA), intermediate (IA) or rapid acetylator (RA) phenotypes. Highly penetrant germline mutations in mismatch repair (MMR) genes are the cause of the disease in hereditary nonpolyposis colorectal cancer (HNPCC). There is no strict correlation between the type of germline mutation in MMR genes and the HNPCC phenotype, but age of tumor onset (AO) in HNPCC has been associated at least in part with different variants in apoptosis-related genes. To clarify the potential modifying role of the NAT2 acetylator status in HNPCC, we performed a multicenter study in 226 individuals with colorectal cancer carrying exclusively pathogenic germline mutations in MSH2 or MLH1. We did not observe any significant difference in the NAT2 acetylator status frequency between HNPCC patients and 107 healthy controls (P