Cigarette Smoking, N-Acetyltransferase 2 Genetic Polymorphisms, and Breast Cancer Risk

Ambrosone, Christine B.; Freudenheim, Jo L.; Graham, Saxon; Marshall, James R.; Vena, John E.; Brasure, John; Michalek, Arthur M.; Laughlin, Rosemary; Nemoto, Takuma; Gillenwater, Kari A.; Harrington, Anita M.; Shields, Peter G.

doi:10.1001/jama.1996.03540180050032

Cited by 252 publications

(110 citation statements)

References 52 publications

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“…Consequently, children carrying NAT2 slow-acetylator genotypes were at an increased risk of developing ALL (OR=1.5, 95%CI 1.0-2.2, P=0.03) [48]. These data are in agreement with studies of solid neoplasias in adults reporting that NAT2 slow-acetylator carriers are at a greater risk of head and neck, breast, laryngeal and bladder cancers [47,[49][50][51][52]. Several studies reported an association of NAT1*10 allele with an increase of N-acetyltransferase activity [45], higher levels of DNA adducts [53] and an elevated risk of colon, bladder, or breast carcinomas [45,54,55].…”

Section: N-acetyltransferase (Nat)supporting

confidence: 79%

Challenges Identifying Genetic Determinants of Pediatric Cancers – the Childhood Leukemia Experience

2006

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Pediatric cancers affect approximately 1 in every 500 children before the age of 15. Little is known about the etiology of this heterogeneous group of diseases despite the fact they constitute the major cause of death by disease among this population. Because of its relatively high prevalence, most of the work done in pediatric oncogenetics has been focused on leukemias, particularly acute lymphoblastic leukemia (ALL). Although it is now well accepted that genetic variation plays a significant role in determining individual's cancer susceptibility, few studies have explored genetic susceptibility to childhood leukemia with respect to common polymorphisms. The biochemical and genetic mechanisms contributing to cancer susceptibility are numerous and can be grouped into broad categories: (1) cellular growth and differentiation, (2) DNA replication and repair, (3) metabolism of carcinogens (4) apoptosis, (5) oxidative stress response and (6) cell cycle. To evaluate whether candidate genes in these pathways are involved in childhood leukemogenesis, we conducted case-control studies. We showed that leukemogenesis in children may be associated with DNA variants in some of these genes and that the combination of genotypes seems to be more predictive of risk than either of them independently. We also observed that, at least at some loci, the parental genetics might be important in predicting the risk of cancer in this pediatric model of a complex disease. Taken together, these results indicate that the investigation of a single enzyme and/or a single genotype might not be sufficient to explain the etiology of childhood leukemia because of the complexity of the environment and that of the inter-individual variability in cancer susceptibility.

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Section: N-acetyltransferase (Nat)supporting

confidence: 79%

Challenges Identifying Genetic Determinants of Pediatric Cancers – the Childhood Leukemia Experience

2006

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“…Of these studies that measured smoking, seven investigated the hypothesized interaction of cumulative smoking exposure (in terms of pack-years) and NAT2 acetylator genotypes [9,10,18,20,24,25,32]. Because two publications [18,25] did not supply enough information of cumulative smoking exposure, only five studies including 2,264 cases and 2,321 controls were used in this subgroup analysis, in which cumulative smoking exposure were categorized as never, low pack-years, or high pack-years.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Because two publications [18,25] did not supply enough information of cumulative smoking exposure, only five studies including 2,264 cases and 2,321 controls were used in this subgroup analysis, in which cumulative smoking exposure were categorized as never, low pack-years, or high pack-years. Low and high pack-years were dichotomized at 20 for 2 studies [9,10], at 15 for other 2 studies [24,32], and at 25 for 1 study [20]. Though the cutoff points for pack-years in these studies were a bit different, the potential risk modification of the effect of NAT2 polymorphisms on breast cancer by cumulative smoking exposure could probably be evaluated.…”

Section: Study Characteristicsmentioning

confidence: 99%

“…Agundez et al firstly reported that the rapid acetylator NAT2 genotypes might be associated with a risk to develop lobular breast cancer, but no support for an association between NAT2 polymorphisms and breast cancer risk was provided [8]. Conversely, Ambrosone et al reported that breast cancer risk was specifically increased in postmenopausal women with the slow acetylator NAT2 genotypes [9]. A series of related studies were carried out later, however, results were generally inconsistent and inconclusive, probably due to the possible small effect of the polymorphisms on breast cancer risk or the relatively small sample size in each of published studies.…”

Section: Introductionmentioning

confidence: 99%

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NAT2 polymorphisms combining with smoking associated with breast cancer susceptibility: a meta-analysis

Zhang

Qiu

Wang

et al. 2010

Breast Cancer Res Treat

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To derive a more precise estimation of the relationship between the slow or rapid acetylation resulting from N-acetyltransferase 2 (NAT2) polymorphisms and breast cancer risk, a meta-analysis was performed. PubMed, Medline, Embase, and Web of Science were searched. Crude odds ratios (ORs) with 95% confidence intervals (CIs) were used to assess strength of association. The pooled ORs were performed for slow versus rapid acetylation genotypes. A total of 26 studies including 9,215 cases and 10,443 controls were included in the meta-analysis. Overall, no significantly elevated breast cancer risk was associated with NAT2 slow genotypes when all studies were pooled into the meta-analysis (OR = 1.026, 95% CI = 0.968-1.087). In the subgroup analysis by ethnicity, increased risks were not found for either Caucasians (OR = 1.001, 95% CI = 0.938-1.068) or Asians (OR = 1.155, 95% CI = 0.886-1.506). When stratified by study design, statistically significantly elevated risk associated with NAT2 slow genotypes was only found among hospital-based studies (OR = 1.178, 95% CI = 1.037-1.339). In the subgroup analysis by menopausal status, no statistically significantly increased risk was found in either premenopausal (OR = 1.053, 95% CI = 0.886-1.252) or postmenopausal women (OR = 0.965, 95% CI = 0.844-1.104). When stratified by cumulative smoking exposure, in the subgroup of smokers with high pack-years, NAT2 slow genotypes were significantly associated with increased breast cancer risk (OR = 1.400, 95% CI = 1.099-1.784). In conclusion, this meta-analysis suggested that there is overall lack of association between NAT2 genotypes and breast cancer risk, however, NAT2 polymorphisms when combining with heavy smoking history may contribute to breast cancer susceptibility.

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“…These agents include radiation exposure during childhood (at high doses encountered during the treatment of Hodgkin's lymphoma and the atomic bombing of Japan) and cigarette smoking (among women who are slow acetylators of cigarette smoke carcinogens). [6][7][8] Other poorly defined environmental agents affect breast cancer incidence as well. The rate of breast cancer varies widely throughout the globe.…”

mentioning

confidence: 99%

The Oncogenetic Basis of Breast Cancer

Parsons¹

2005

Breast Cancer

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Cigarette Smoking, N-Acetyltransferase 2 Genetic Polymorphisms, and Breast Cancer Risk

Cited by 252 publications

References 52 publications

Challenges Identifying Genetic Determinants of Pediatric Cancers – the Childhood Leukemia Experience

Challenges Identifying Genetic Determinants of Pediatric Cancers – the Childhood Leukemia Experience

NAT2 polymorphisms combining with smoking associated with breast cancer susceptibility: a meta-analysis

The Oncogenetic Basis of Breast Cancer

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