Kouhkan F, Motovali-Bashi M, Hojati Z
Genetics Division, Biology Department, Faculty of Sciences, Isfahan University, Isfahan, Iran.
Cancer Invest. 2008 Oct;26(8):836-42. doi: 10.1080/07357900801953204.
Interstitial collagenase-1 degrades a variety of extracellular matrix components. A single guanine insertion polymorphism in the promoter has been found that influences on the transcription and expression level of the gene. It is suggested that this polymorphism may enhance susceptibility to some types of cancer. Therefore, this case-control study evaluated the association of this genotype polymorphism with susceptibility to initiation and invasion of colorectal cancer. For this reason, whole blood samples were obtained from 150 CRC patients and 100 control subjects in Tehran. Genomic DNA was extracted and genotyped by PCR-RFLP method. We showed that 2G allele and 2G/2G genotype had higher frequencies in patients (60% and 39%, respectively) than in controls (47% and 23%, respectively). The CRC patients were divided into two groups: with metastasis (M+) and without metastasis (M-) groups. The 2G allele was more frequent in M+ group compared with control group. However, no significantly difference was observed between M-group and control (chi(2) = 0.48, P = 0.78 for 2G/2G genotype). Further stratification analyses showed that only gender (OR = 2.58, 95% CI = 0.89-7.52 for women and OR = 4.12, 95% CI = 1.62-10.42 for men) and smoking (OR = 3.03, 95% CI = 1.28-7.16 for non-smokers and OR = 4.09, 95% CI = 1.18-4.15 for smoker) may modify the risk of colorectal invasion related to 2G/2G genotype. Furthermore, individual with 2G/2G genotype seems to spread metastasis, 3 years earlier than those who were 1G/1G and 1G/2G. In conclusion, to our knowledge, the present epidemiological study for the first time indicates the relationship of 2G/2G genotype polymorphism with invasion risk of colorectal cancer in subgroups of gender and smoking, especially in smoker men.
间质胶原酶-1可降解多种细胞外基质成分。已发现启动子区存在一个单鸟嘌呤插入多态性，其会影响该基因的转录和表达水平。有研究表明，这种多态性可能会增加某些类型癌症的易感性。因此，本病例对照研究评估了这种基因型多态性与结直肠癌发生和侵袭易感性之间的关联。为此，从德黑兰的150例结直肠癌患者和100例对照者中采集了全血样本。通过PCR-RFLP方法提取基因组DNA并进行基因分型。我们发现，患者中2G等位基因和2G/2G基因型的频率（分别为60%和39%）高于对照组（分别为47%和23%）。结直肠癌患者分为两组：有转移（M+）组和无转移（M-）组。与对照组相比，M+组中2G等位基因更为常见。然而，M-组与对照组之间未观察到显著差异（2G/2G基因型的χ² = 0.48，P = 0.78）。进一步的分层分析表明，只有性别（女性的OR = 2.58，95% CI = 0.89 - 7.52；男性的OR = 4.12，95% CI = 1.62 - 10.42）和吸烟（非吸烟者的OR = 3.
