인체 방광암에 있어서 NAT2 및 GSTM1 다형성에 따른 p53 및 H-ras 유전자의 돌연변이 양상
Occurrence and Specific Type of p53 rind H-ras Mutations Based on Polymorphisms of NAT2 and GSTMI in Human Bladder Cancer
김원재, 이상철, 우승효, 이종걸,
소속 상세정보
김원재 ( )
Chungbuk National University
이상철 ( )
Chungbuk National University
우승효 ( )
Chungbuk National University
이종걸 ( )
Chungbuk National University
KMID : 0358319990400070869
Abstract
결론
종양의 발생에는 암유전자나 종양억제유전자의 변이가 관여하게 되는데 방광암의 경우
p53이나 H-ras유전자의 변이가 빈번하게 관찰된다. 특히 외부의 발암물질과 밀접한 관계가
있는 점으로 미루어 보아 이론적으로는 이물질 대사 관련 유전자의 다형성은 여러 종양 발
생 관련 유전자의 변화에 관여할 것으로 여겨진다. 저자들의 실험에서는 NATE와 GSTM1
의 다형성은 p53과 H-ras 유전자 돌연변이 발생과 무관하였으며 또한 돌연변이 형태에 대
하여서도 관련성을 가지고 있지 않았다. 이러한 결과는 이물질 패사 관련 효소의 변화와 방
광암에서 p53이나 H-ras유전자의 변화는 상호 독립적임을 나타내는 것이다. 그러나 일부
상반된 보고가 있는 점을 감안할 때 다양한 경로의 다른 기전들이 관여하지 않을까 추측되
며, 앞으로 많은 증례를 추가하여 체계적인 조사를 실시함으로서 이 기전들을 밝히는데 도
움이 줄 수 있으리라 생각된다.
Purpose: Cancer development depends on not only activation of oncogene or
inactivation of tumor suppressor gene but also activities of enzymes involved in the
metabolism of various carcinogenic xenobiotics, such as arylamine N-acetyltrasferase
2(NAT 2) and glutathione S-transferase(GSTM1). We analyzed whether genetic
polymorphisms of NAT2 and GSTMI were correlated with the mutation patterns of p53
and H-ras genes in bladder tumor tissues.
Materials and Methods: In 49 bladder cancer patients, we performed direct DNA
sequencing for the detection of mutations of p53 and H-ras gene in bladder tumor
tissues, and adopted PCR and PCR-RFLP techniques for the analysis of genetic
polymorphisms of NAT2 and GSTM 1 using patients blood samples, respectively.
Results: In 18 cases, mutations in p53 were detected whereas 1 case carried two
mutations; thus total of 19 mutations were detected. Sixteen of these were point
mutations including 13 of transversions and 3 of transitions, and others were 1 of
frameshift and 2 of microdeletions-insertions. Among 33 patients, H-ras mutations were
detected in 5 cases with 2 of transitions and 3 of transversions. The frequencies of
slow, intermediate, and rapid acetylator in NAT2 genotyping analysis, were 10.2%,
40.8%, and 49.0%, respectively, and GSTM1 deletions were observed in 73.5%. We could
not find any significant correlations between NAT2 or GSTM1 polymorphisms and the
occurence of p53(p=0.614, p=0.310) or H-ras(p=0.500, p=0.582) mutations. Also, no
apparent associations were seen for specific type of p53 and H-ras mutations according
to Polymorphisms of NAT2(p=0.456, p=0.600) and GSTM1(p=0.378, p=0.400).
Conclusions: The polymorphisms of NAT2 and GSTM1, conjugating enzymes of
foreign compound metabolism, were not considered to influence occurrence and type of
mutations in p53 and H-ras in human bladder cancer.
키워드
Bladder cancer; p53; H-ras; NAT2; GSTM1;
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