PMID- 9626964
OWN - NLM
STAT- MEDLINE
DCOM- 19980624
LR  - 20190702
IS  - 0027-5107 (Print)
IS  - 0027-5107 (Linking)
VI  - 398
IP  - 1-2
DP  - 1998 Feb 26
TI  - Association of the NAT1*10 genotype with increased chromosome aberrations and 
      higher lung cancer risk in cigarette smokers.
PG  - 43-54
AB  - The NAT1 gene exhibits polymorphisms in the non-coding polyadenylation region 
      with a number of alleles. Of these alleles, NAT1*10 is responsible for increased 
      NAT1 enzyme levels and is reported to be associated with increased risk for 
      colorectal and bladder cancers. In view of the possible role of the NAT1 gene 
      product in the metabolism of a number of cigarette smoke carcinogens, we tested 
      the possibility that genetic variation in the NAT1 gene might also be associated 
      with increased risk for lung cancer. Allelic variances of the NAT1 gene were 
      analyzed in 45 lung cancer patients and 47 controls who were matched with respect 
      to age, race and gender using restriction fragment length polymorphism (RFLP) 
      analysis and allele-specific (AS)-PCR. Our results indicate that individuals who 
      inherited the NAT1*10 allele had a 3.7-fold increased relative risk for lung 
      cancer (95% CL = 1.2-16.0, p < 0.02). There was a 6.8-fold increase in relative 
      risk for lung cancer associated with the inheritance of the NAT1*10 allele in 
      younger individuals (< 60 years of age) compared to 2.2-fold increase in older 
      individuals (> 60 years old) (OR = 6.8; 95% CL = 1.1-40.7, p < 0.01 and OR = 2.2; 
      95% CL = 0.5-11.1, p = 0.2, respectively). We have also applied the sensitive 
      fluorescence in situ hybridization (FISH) tandem probe assay to elucidate the 
      frequency of chromosome breakage among a subgroup of the studied individuals 
      harboring the NAT1*10 allele (17 lung cancer patients, 17 smoking controls and 7 
      non-smoking controls). Our results indicate a significant increase (p < 0.001) in 
      the frequency of chromosome breaks in lung cancer patients (mean +/- SE per 100 
      cells = 1.45 +/- 0.11) and in smoking controls (1.30 +/- 0.13) compared to 
      non-smoking controls (0.47 +/- 0.07). Regression analysis indicated a highly 
      significant positive correlation between the duration of smoking in years and the 
      frequency of chromosome breaks in lung cancer patients (r = 0.62, p = 0.008), but 
      not in smoking controls (r = 0.02; p = 0.91). These findings suggest that NAT1 
      polymorphism may be an important genetic determinant of lung cancer risk. In 
      addition, these data provide a mechanistic link between the inheritance of the 
      NAT1*10 allele and smoking-induced lung cancer. Given that the NAT1 enzyme can 
      mediate activation and detoxication pathways for numerous carcinogens and given 
      that this polymorphism is prevalent in the general population (20-50% frequency), 
      it may play a significant role in influencing the outcome of a variety of 
      environmental cancers.
FAU - Abdel-Rahman, S Z
AU  - Abdel-Rahman SZ
AD  - Department of Preventive Medicine and Community Health, Galveston, TX 77555, USA.
FAU - El-Zein, R A
AU  - El-Zein RA
FAU - Zwischenberger, J B
AU  - Zwischenberger JB
FAU - Au, W W
AU  - Au WW
LA  - eng
GR  - P30 ES 06676/ES/NIEHS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, Non-P.H.S.
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Mutat Res
JT  - Mutation research
JID - 0400763
RN  - 0 (Isoenzymes)
RN  - EC 2.3.1.- (Acetyltransferases)
RN  - EC 2.3.1.5 (Arylamine N-Acetyltransferase)
RN  - EC 2.3.1.5 (N-acetyltransferase 1)
SB  - IM
MH  - Acetyltransferases/*genetics
MH  - Aged
MH  - *Arylamine N-Acetyltransferase
MH  - *Chromosome Aberrations
MH  - Gene Frequency
MH  - Genetic Predisposition to Disease
MH  - Genotype
MH  - Humans
MH  - Isoenzymes
MH  - Lung Neoplasms/epidemiology/*genetics
MH  - Middle Aged
MH  - Polymorphism, Genetic
MH  - Risk Factors
MH  - Smoking/*genetics
EDAT- 1998/06/17 00:00
MHDA- 1998/06/17 00:01
CRDT- 1998/06/17 00:00
PHST- 1998/06/17 00:00 [pubmed]
PHST- 1998/06/17 00:01 [medline]
PHST- 1998/06/17 00:00 [entrez]
AID - S0027-5107(97)00238-8 [pii]
AID - 10.1016/s0027-5107(97)00238-8 [doi]
PST - ppublish
SO  - Mutat Res. 1998 Feb 26;398(1-2):43-54. doi: 10.1016/s0027-5107(97)00238-8.