N-Acetyltransfsrase 2와 Glutathione S-Transferase mu 유전자 다형성이 방광암 발생에 미치는 영향
The Effects of the Genetic Polymorphisms of N-acetyltransferase 2 and Glutathione S-transferase mu on the Development of Bladder Tumor
소속 상세정보
김원재/Wun Jae Kim
김헌/이형래/김청수/최한용/Heon Kim/Hyung Lae Lee/Choung Soo Kim/Han Yong Choi
KMID : 0358319990400030308
Abstract
결론
1996년 3월부터 1996년 12월까지 충북대학교병원과 삼성의료원, 그리고 서울중앙병원 비
뇨기과에 입원하여 치료를 받은 방광암 환자 113명과, 암 아닌 다른 질환을 가진 대조군
221명을 대상으로 흡연, 음주, 직업력, 질병력 등을 포함한 생활 습관과 NAT2와 GSTM1
유전자 다형성 양상을 조사하여 다음과 같은 결론을 얻었다.
NAT2의 활성과 방광암 위험도 사이의 관련성은 유의하지 않았다(χ
2trend=3.12, p-value>0.05). 또한 GSTM1 결손은 방광암 발생
의 위험인자로 나타났다. 흡연 여부는 방광암의 발생에 유의한 영향을 미치지 않는 것으로
나타났는데 이는 환자군과 대조군의 흡연률이 모두 높기 때문으로 판단된다. 결핵과 기관지
천식의 과거력은 방광암에 대한 유의한 위험인자로 나타났으며, NAT2와 GSTM1 유전자
다형성과 흡연 여부 등을 통제한 다변량 분석에서도 통계적으로 유의하였다. 그 외, 음주력,
직업력, 수혈여부, 그리고 피임시술의 과거력 등의 요인들은 방광암 발생과 유의한 관련성이
없는 것으로 나타났다. 통계적으로 유의한 것으로 나타난 수혈 여부는 방광암 치료과정과
관련있는 것으로 보인다.
Purpose: Activity of enzymes involved in the metabolism of various carcinogenic
xenobiotics is one of the most important host factor for cancer occurrence.
N-acetyltransferase(NAT) and glutathione S-transferase(GST) are enzymes which
reduce the toxicity of activated carcinogenic metabolites. Slow N-acetylaion and lack of
glutathione S-transferase mu(GSTM1) were reported as risk factors of bladders tumor.
Since the cause of bladder cancer is not fully explained by single risk factor, many
kinds of enzymes would be involved in the metabolism of carcinogens excreted in urine.
This study was performed to investigate whether the polymorphisms of
N-acetyltransferase type 2(NAT2) and GSTM1 are risk factors of bladder tumor and to
evaluate the effects of their interaction on bladder tumor development.
Materials and Methods: 113 bladder tumor and 221 non-cancer patients, hospitalized in
the Chungbuk National University Hospital, Samsung Medical Center, and Asan Medical
Center from March to December 1996 participated in this case-control study.
Questionnaire interview was done and the genotypes of NAT2 and GSTM1 were
identified using PCR methods with DNA extracted from the venous blood. The effects
of the polymorphism of NAT2 and GSTM1 and their interaction on bladder cancer were
statistically tested after controlling the other risk factors.
Results: The frequencies of slow, intermediate, and rapid acetylators were 7.1%, 37.5%,
and 55.4% for the cases, and 11.0%, 43.4%, and 45.7% for the controls, respectively. The
risk of bladder tumor was not associated with the increase of NAT2 activity (χ
2trend=3.16, p-value>0.05). GSTM1 was deleted in 69.6% of
the cases and 55.9% of the controls(χ2=5.86, p-value<0.05), and the odds
ratio(95% Cl) was 1.81(1.12-2.93). Smoking history fumed out to be insignificant as a
risk factor of bladder tumor(OR=1.34, 95%Cl: 0.78-2.31), and occupation could not be
tested because of the extremely small number of occupational history related to the
increase of bladder tumor. Medical history of tuberculosis and bronchial asthma were
significant risk factors for bladder tumor, and their ORs(95% Cl) were 3.61(1.57-8.26)
and 4.15(1.61-10.75), respectively. In multiple logistic analysis controlling the effects of
other risk factors, GSTM1 deletion(OR: 1.80, 95% Cl: 1.07-3.05), and histories of
tuberculosis(OR: 2.99, 95% Cl: 1.22-7.32) and of bronchial asthma(OR: 3.38, 95% Cl:
1.24-9.22) were the significant risk factors for bladder tumor, but slow acetylation was
not.
Conclusions: These results suggest that GSTM1 deletion may be a significant risk
factor of bladder tumor. The medications for tuberculosis and bronchial asthma could
possibly cause bladder tumor, or immune mechanism might be involved in the
development of bladder tumor.
키워드
Bladder tumor; N-acetyltransferase 2; Glutathione S-transferase mu;
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