NAT2 slow acetylator genotype is associated with increased risk of lung cancer among non-smoking Chinese women in Singapore

Abstract

Among non-smokers, the factors resulting in lung carcinogenesis are poorly understood. We conducted a hospital-based case-control analysis of 294 Chinese women, of whom 217 were non-smokers, to evaluate the role of polymorphic N-acetyltransferase (NAT2) as a susceptibility factor for the disease. The proportion of slow acetylator genotypes among non-smoking cases (n = 92) and controls (n = 125) was 38.0 and 24.0%, respectively [odds ratio (OR) 2.0, 95% confidence interval (CI) 1.1-3.7]. No effect of NAT2 genotype was seen among smokers. Among non-smokers, the effect was marked for adenocarcinomas (OR 2.1, 95% CI 1.1-4.0). As NAT2 activity is known to modify risk of arylamine-induced carcinogenesis, our results suggest that exposure to arylamines in the environment may play a role in risk of lung cancer among non-smokers.

Polymorphism of selected enzymes involved in detoxification and biotransformation in relation to lung cancer

“…Nevertheless, authors seem to confirm a modulatory effect of smoking status on NAT2-associated lung cancer risk (Table 8). While in non-smokers, the slow acetylator phenotype determining genotypes seem to be associated with increased risk of lung cancer, among smokers, such genotypes are rather protective [133,134]. In consent with this seems to be the conclusion, that the fast acetylator genotypes comprise a risk factor for heavy smokers (OR = 1.22; 95% CI: 0.89-1.67), while provide protection against lung cancer among nonsmokers (OR = 0.66; 95% CI: 0.79-1.16).…”

Genetic susceptibility to tobacco-related cancer

“…Studies have been conflicting with regard to the association with lung cancer risk. Most studies report no overall increase in risk with either the slow or fast acetylators (Philip et al, 1988;Martinez et al, 1995;Bouchardy et al, 1998;Saarikoski et al, 2000), whereas a few have reported increased risk with either the slow (Oyama et al, 1997;Seow et al, 1999) or fast acetylator genotype. In the largest study of 1115 lung cancer patients and 1250 controls, no association was found between the NAT2 genotype and lung cancer risk (Zhou et al, 2002b).…”

NAT2*7 Allele Is a Potential Risk Factor for Adult Brain Tumors in Taiwanese Population

“…Individuals, with combined NAT1 rapid and NAT2 slow genotype, seemed to have a significantly higher risk for lung adenocarcinoma (23), or the NAT2 slow genotype when combined with the GSTM1-null genotype may increase the susceptibility to adduct formation, gene mutation, and lung cancer risk (24). Similarly, a combination of NAT2 slow/CYP1A1 rapid acetylator may also predispose higher risk to lung cancer in nonsmoking females (11). Although there is no single polymorphism able to predict the risk of brain tumors, an allelic combination could jointly affect the risk of brain tumors (13,25).…”

“…Slow acetylator phenotypes caused by polymorphisms in NAT2 gene confer a higher risk of bladder cancer due to the reduced activity in the hepatic N-acetylation pathway, which detoxifies compounds such as 4-aminobiphenyl and competes with N-oxidation of these compounds by cytochrome P4501A2 to reactive hydroxylamines. The relationship between the polymorphism of NAT2 and other cancers such as lung and colorectal cancer has also been studied (5)(6)(7)(8)(9)(10)(11).…”