Effect of SULT1A1 and NAT2 genetic polymorphism on the association between cigarette smoking and colorectal adenomas.
Cigarette smoke contains polycyclic hydrocarbons and arylamines that may both be activated by sulfotransferase, encoded by SULT1A1. A genetic polymorphism leads to an Arg213His substitution, thereby decreasing enzyme activity and stability and might thus modify the association between smoking and colorectal adenomas. We investigated this in a Dutch case-control study. Additionally, we evaluated potential roles of epoxide hydrolase (EPHX), N-acetyltransferases (NAT1 and NAT2) and glutathione S-transferases (GSTM1 and GSTT1). The data analysis included 431 adenoma cases and 432 polyp-free controls (54% women; mean age, 54.6 years) enrolled at endoscopy in 8 Dutch hospitals between 1997 and 2000. All participants provided data on smoking habits and blood for DNA isolation. Genotyping was performed using appropriate polymerase chain reaction-restriction fragment length polymorphism procedures. Multivariate models included age, sex, endoscopy indication, consumption of snacks and alcohol and, if appropriate, daily smoking dose or smoking duration. Smoking increased colorectal adenoma risk, most importantly by duration. Smoking for more than 25 years more than doubled adenoma risk (OR = 2.4, 95% CI = 1.4-4.1) compared to never smoking. Combinations of SULT1A1 fast sulfation (*1/*1) and of NAT2 slow acetylation with smoking resulted in a 4 times higher risk of adenomas compared to never smokers with other inherited gene variants, although there was no statistically significant effect modification. We found no clear effects of the other genetic polymorphisms on the association between smoking and adenomas. We conclude that smoking increases risk of colorectal adenomas and that SULT1A1 and NAT2 only modestly modify this association.
Tiemersma
Edine W
EW
Division of Human Nutrition and Epidemiology, Wageningen University, Wageningen, The Netherlands.
Bunschoten
Annelies
A
Kok
Frans J
FJ
Glatt
Hansruedi
H
de Boer
Sybrand Y
SY
Kampman
Ellen
E
D000123:Acetyltransferases / Q000235:genetics; D000236:Adenoma / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D000368:Aged; D001191:Arylamine N-Acetyltransferase / Q000235:genetics*; D015239:Arylsulfotransferase; D016022:Case-Control Studies; D015179:Colorectal Neoplasms / Q000235:genetics*; D004851:Epoxide Hydrolases / Q000235:genetics; D005260:Female; D006801:Humans; D007527:Isoenzymes; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012907:Smoking; D015238:Sulfotransferases / Q000235:genetics*
D007527:Isoenzymes; D000123:Acetyltransferases; D001191:Arylamine N-Acetyltransferase; C089384:N-acetyltransferase 1; C478900:NAT2 protein, human; D015238:Sulfotransferases; D015239:Arylsulfotransferase; C117544:SULT1A1 protein, human; D004851:Epoxide Hydrolases