The 2G allele of promoter region of matrix metalloproteinase-1 as an essential pre-condition for the early onset of oral squamous cell carcinoma.
The 2G allele of promoter region of matrix metalloproteinase-1 as an essential pre-condition for the early onset of oral squamous cell carcinoma.
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DOI：
10.1186/1471-2407-7-187
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发表时间：
2007-10-05
期刊：
影响因子：
3.8
通讯作者：
Takagi, Ritsuo
中科院分区：
文献类型：
--
作者：
Nishizawa, Rishiho;Nagata, Masaki;Noman, Arhab A.;Kitamura, Nobutaka;Fujita, Hajime;Hoshina, Hideyuki;Kubota, Takehiko;Itagaki, Manami;Shingaki, Susumu;Ohnishi, Makoto;Kurita, Hiroshi;Katsura, Kouji;Saito, Chikara;Yoshie, Hiromasa;Takagi, Ritsuo
基质金属蛋白酶(MMPs)被认为参与了癌症发展的初期和进展期，以及癌症的侵袭性表型。本研究探讨了基质金属蛋白酶-1和基质金属蛋白酶-3启动子区域的单核苷酸多态与口腔鳞癌易感性的关系。我们比较了170例日本口腔鳞状细胞癌患者和164例健康对照的基质金属蛋白酶-1和基质金属蛋白酶-3的基因分型。口腔鳞癌患者中2G等位基因频率较高，1G纯合子频率较低(p=0.034)。多因素Logistic回归分析显示，年龄在45岁以上的受试者患口腔鳞癌的风险增加了2.47倍(95%CI1.47-4.14，p=0.0006)，携带MMP一2G等位基因的受试者患口腔鳞癌的风险增加了2.30倍(95%CI1.15-4.58，p=0.018)。本研究的主要发现之一是，在45岁以下的早发性口腔鳞癌患者中，MMP-1的1G/1G和1G/2G基因型分布明显减少。应该指出的是，在这些早发病例中，86.2%的病例以舌头为主要部位。这可能暗示了特定的致癌机制，即特定的致癌刺激和/或舌头中的遗传因素。由于在一般人群中，2G等位基因是基质金属蛋白酶-1基因的大多数，因此它似乎是口腔鳞癌发生的遗传前提条件。然而，这份报告表明，基质金属蛋白酶-1的2G等位基因在早期发病的口腔鳞癌中起着至关重要的作用。
Matrix metalloproteinase (MMP) is known to be involved in the initial and progressive stages of cancer development, and in the aggressive phenotypes of cancer. This study examines the association of single nucleotide polymorphisms in promoter regions of MMP-1 and MMP-3 with susceptibility to oral squamous cell carcinoma (OSCC). We compared 170 Japanese OSCC cases and 164 healthy controls for genotypes of MMP-1 and MMP-3. The frequency of the MMP-1 2G allele was higher and that of the 1G homozygote was lower in the OSCC cases (p = 0.034). A multivariate logistic regression analysis revealed that subjects who were 45 years old or older had a significantly increased (2.47-fold) risk of OSCC (95%CI 1.47–4.14, p = 0.0006), and those carrying the MMP-1 2G allele had a 2.30-fold risk (95%CI 1.15–4.58, p = 0.018), indicating independent involvement of these factors in OSCC. One of the key discoveries of this research is the apparent reduction of the MMP-1 1G/1G and 1G/2G genotype distributions among the early onset OSCC cases under the ages of 45 years. It should be noted that the tongue was the primary site in 86.2% of these early onset cases. This could suggest the specific carcinogenic mechanisms, i.e. specific carcinogenic stimulations and/or genetic factors in the tongue. Since the 2G allele is a majority of the MMP-1 genotype in the general population, it seems to act as a genetic pre-condition in OSCC development. However this report suggests a crucial impact of the MMP-1 2G allele in the early onset OSCC.
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影响因子：
56.9
作者：
NISHISHO, I;NAKAMURA, Y;VOGELSTEIN, B
通讯作者：
VOGELSTEIN, B
DOI：
10.1111/j.1349-7006.2000.tb00989.x
发表时间：
2000-06-01
期刊：
JAPANESE JOURNAL OF CANCER RESEARCH
影响因子：
--
作者：
Nishioka, Y;Kobayashi, K;Kudo, R
通讯作者：
Kudo, R
影响因子：
6.2
作者：
Shiboski, CH;Schmidt, BL;Jordan, RCK
通讯作者：
Jordan, RCK
影响因子：
6.4
作者：
Liang, G;Xing, DY;Lin, DX
通讯作者：
Lin, DX
影响因子：
3.3
作者：
Lin, SC;Chung, MY;Chang, KW
通讯作者：
Chang, KW