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NAT2 slow acetylator genotype as an important modifier of breast cancer risk
Author(s) -
Sillanpää Pia,
Hirvonen Ari,
Kataja Vesa,
Eskelinen Matti,
Kosma VeliMatti,
Uusitupa Matti,
Vainio Harri,
Mitrunen Katja
Publication year - 2004
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.20677
Subject(s) - breast cancer , genotype , odds ratio , medicine , confidence interval , allele , oncology , cancer , carcinogen , body mass index , population , case control study , physiology , genetics , gynecology , gastroenterology , biology , gene , environmental health
N ‐acetyltransferase 2 (NAT2) is a polymorphic enzyme participating in the metabolism of numerous pharmaceutical drugs and carcinogens found in tobacco smoke and diet. The NAT2 gene is highly polymorphic and several different allelic variants exist that determine the acetylator phenotype. In the course of our case–control study, we developed a new method based on fluorogenic allele‐specific probes for analyzing the C 282 T and T 341 C polymorphisms of the NAT2 gene in 483 Finnish breast cancer patients and 482 healthy population controls. The slow NAT2 acetylation capacity–associated genotypes posed a somewhat increased overall breast cancer risk (odds ratio [OR], 1.32; 95% confidence interval [CI], 1.01–1.73). This association was found to be confined to the advanced (stage III or IV) breast cancer (OR, 2.60; 95% CI, 1.29–5.24). When stratified by smoking habits, women who had smoked <5 pack‐years and carried a NAT2 slow acetylator genotype were at a 2.6‐fold (OR, 2.55; 95% CI, 1.01–6.48) risk of breast cancer. Moreover, women with the NAT2 slow acetylator genotype and low body mass index (BMI) (<25.4 kg/m 2 ) were at somewhat increased risk of this malignancy (OR, 1.60; 95% CI, 1.07–2.39). Our results therefore suggest that NAT2 slow acetylator genotype may be an important modifier of environmentally induced breast cancer risk in Finnish women. © 2004 Wiley‐Liss, Inc.