Rapid N-acetyltransferase 2 imputed phenotype and smoking may increase risk of colorectal cancer in women (Netherlands).
OBJECTIVE
The relationship between smoking and colorectal cancer risk and whether such effect is modified by variations in the NAT2 genotype is investigated.


METHODS
In the prospective DOM (Diagnostisch Onderzoek Mammacarcinoom; 27,722 women) cohort follow-up from 1976 until 1987 revealed 54 deaths due to colon or rectal cancer, and follow-up from 1987 to 01-01-1996 revealed 204 incident colorectal cancer cases. A random sample (n = 857) from the baseline cohort was used as controls. Four NAT2 restriction fragment length polymorphisms (RFLPs) were analysed using DNA extracted from urine samples. Rapid or slow acetylator phenotype status was attributed to individuals.


RESULTS
Smoking may increase the risk for colon cancer (RR = 1.36, 95% CI 0.97-1.92) as well as for rectal cancer (RR = 1.31, 95% CI 0.76-2.25), although not statistically significant. Rapid NAT2 acetylation did not increase colorectal cancer risk, but in combination with smoking the risk was statistically significant increased, compared to women who had a slow NAT2 imputed phenotype and never smoked (RR = 1.56, 95% CI 1.03-2.37). For colon cancer, but not for rectal cancer the increased risk was statistically significant (RR = 1.67, 95% CI, 1.05-2.67 versus RR = 1.30 95% CI 0.63-2.68).


CONCLUSIONS
Our study points to smoking as a risk factor for colon and rectal cancer and, in addition, especially in women with rapid NAT2 imputed phenotype.
van der Hel
Olga L
OL
Julius Center for Health Sciences and Primary Care, University Medical Centre, Utrecht, 3508 GA Utrecht, The Netherlands.
Bueno de Mesquita
H Bas
HB
Sandkuijl
Lodewijk
L
van Noord
Paul A H
PA
Pearson
Peter L
PL
Grobbee
Diederick E
DE
Peeters
Petra H M
PH
D001191:Arylamine N-Acetyltransferase / Q000235:genetics / Q000494:pharmacology*; D015331:Cohort Studies; D003110:Colonic Neoplasms / Q000453:epidemiology / Q000209:etiology*; D005260:Female; D006801:Humans; D015994:Incidence; D007700:Kinetics; D008875:Middle Aged; D010641:Phenotype; D011446:Prospective Studies; D012004:Rectal Neoplasms / Q000453:epidemiology / Q000209:etiology*; D012907:Smoking / Q000009:adverse effects*
D001191:Arylamine N-Acetyltransferase; C478900:NAT2 protein, human