Genetic variation in N-acetyltransferases 1 and 2, cigarette smoking, and risk of non-Hodgkin lymphoma.
Cigarette smoke contains many carcinogens that are metabolically activated through xenobiotic metabolism by phase I and II enzymes, including N-acetyltransferases 1 and 2 (NAT1 and NAT2). We investigated non-Hodgkin lymphoma risk in general and by subtype in relation to NAT1 and NAT2 genotypes and cigarette smoking in a population-based case-control study in Connecticut. Of the 535 controls, 53.1% reported ever smoking, and of the 461 cases, 55.7% reported ever smoking. We found a two-fold increased risk of T-cell lymphoma among those possessing the NAT1*10 genotype compared to those with other NAT1 genotypes; including an OR of 2.0 (95% CI: 1.0-2.4) for those heterozygous or homozygous for NAT1*10 genotypes. Rapid acetylator NAT2 phenotype increased the risk of both T-cell lymphoma (OR = 3.2; 95% CI: 1.1-9.5) and marginal zone lymphoma (OR = 3.0; 95% CI: 1.0-8.7), though these results were based on a small number of cases. When smoking status and risk of NHL was stratified by NAT1 and NAT2 genotypes, an increased risk of NHL overall was observed in current (OR = 1.7; 95% CI: 1.2-2.4) smokers without the NAT1*10 genotype but not among smokers with the NAT1*10 genotype (p-interaction < 0.01). No association between history of cigarette smoking and risk of NHL overall was observed with any NAT2 genotype. Our results present modest evidence that acetylation rate is associated with risk of NHL for specific subtypes and that the NAT1*10 genotype is an "at-risk" allele. Additionally, our results suggest that the relationship between NHL and smoking status may be modified by common genetic variation in NAT1 but not NAT2. We conclude that these findings require replication in larger studies and ultimately in pooled analyses.
Kilfoy
Briseis A
BA
Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Rockville, MD, USA. kilfoyb@mail.nih.gov
Zheng
Tongzhang
T
Lan
Qing
Q
Han
Xuesong
X
Holford
Theodore
T
Hein
David W
DW
Qin
Qin
Q
Leaderer
Brian
B
Morton
Lindsay M
LM
Yeager
Meredith
M
Boyle
Peter
P
Zhao
Ping
P
Chanock
Stephen
S
Rothman
Nathaniel
N
Zhang
Yawei
Y
D000328:Adult; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D007527:Isoenzymes / Q000235:genetics* / Q000378:metabolism; D008228:Lymphoma, Non-Hodgkin / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012907:Smoking / Q000009:adverse effects*
D007527:Isoenzymes; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human