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acetylators >13@. The
NAT2
genotyping was detected by a modification of the methods of
Bell et al. >12@. The
NAT2*5A
, *
5B, *5C
, *
6
and *
7
alleles were detected. The rapid
acetylators of
NAT2
allele frequencies in cases and controls were 50%-43.7% and slow
acetylators of
NAT2
allele frequencies were 50%-56.3%, respectively. The frequency of
rapid genotype in cases was slightly more common than controls, although there was no
significant difference in the genotype frequency of the
NAT2
rapid allele between two
groups >the adjusted OR; 0.78 (95% CI 0.44-1.38, p=0.39)@. The most common slow allele
was the
NAT2*5B
allele in both cases (38.1%) and controls (38.9%). Among the
*5B
slow
alleles in cases (25%),
*5B/*6
was slightly higher than among controls (21.4%), whereas
5B/*5B
slow allele in cases (9.5%) was slightly lower than among controls (14.6%). The
second most frequent slow allele,
NAT2*6/*6
was the same as among cases (9.5%) and
controls (10.7%). Slightly less controls (43.7%) than cases (50%) had the wild allele
NAT2*4.
Some 8.3% of the cases and 6.8% of all controls were homozygous rapid allele
carriers (
*4/*4
). Only four and one case subject were found to be *4/*5C,
*12A/*12C
,
respectively, whereas no control subject was found. Only three controls were found to be
*6/*7, whereas no case subject was found.
When
NAT2 slow
allele was combined with either
COMT-HL
and
COMT-LL
or
CYP1B1*1/*3
and *
3/*3
genotypes and all gene-gene interaction together, the risk for
developing breast cancer was not significantly increased OR 1.30 (95% CI= 0.71-2.37), OR
0.93 (95% CI= 0.52-1.65) and OR 1.28 (95% CI= 0.55-2.96), respectively.
Most of the information has been collected up to now on the effect of genetic
polymorphism on the individual ability to activate and deactivate estrogens and
xenobiotics, whereas no information is available on inter-individual variability of to
CYP1B1
,
COMT, MnSOD
and
NAT2
genotypes and the influence of these genotypes on
onset of menarche / menapause in Turkish healthy women. These genes were examined
stratified different risk factors in 103Turkish women. In all genotypes, only the case of
COMT, the
COMT-L
(
COMT*2
) allele was more frequent among postmenopausal women
associated with a significantly increased (
X
2
=3.820, p=0.05). However, in the cases of other
genes, the
CYP1B1*3
,
MnSOD Ala
and
NAT2 slow
alleles, there were no significant
differences in the frequency of premenopausal and postmenopausal women >
X
2
=0.360,
p=0.55;
X
2
=0.026, p=0.87;
X
2
=0.653, p=0.42; respectively@. The frequencies of
CYP1B1*3
allele (0.27),
COMT-L
allele (0.39)
MnSOD
Ala allele (0.56) and
NAT2 slow
allele (0.56)
determined in Turkish healthy women were found to be similar with Caucasian population-
based studies. The comparision of genotype frequencies according to the basis of BMI,
there were not any significant differences in each genes. However,
CYP1B1*3
and
COMT*1
genotypes were related to increased risk among women with a BMI greater than
27 kg/m
2
(Fisher's exact test, p=0.044 ).
COMT
,
MnSOD
genotypes stratified for
according to
CYP1B1
genotypes (gene-gene interaction), age and menopausal status;
CYP1B1*3
,
COMT-L
and
MnSOD Ala
alleles does approach significance in older than 45
years and postmenopausal women with compared with the combination of the low risk
genotypes (Fisher's exact test, p=0.012). The correlation between genotype and early age at
menarche was significant in women who carried both
CYP1B1*3
and
COMT-L
alleles than
the women who carried wild alleles (
X
2
=4.57, p=0.032). Although the small sample size of
each combination of estrogen metabolizing, the results suggest that the
CYP1B1*3
and
COMT-L
alleles influence age at menarche in healthy Turkish women.
The study of the relationship among human genetic polymorphisms, cancer
susceptibility will undoubtedly have increasingly important implications for risk
assessment and the prevention, early diagnosis, and intervention of clinical disease and
cancer. There is evidence for the existence of polymorphism in each of the genes encoding
these enzymes and it is possible that combinations of polymorphic enzymes may be better
predictors of cancer risk than polymorphisms in one or two genes alone. Also, the variety of
