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乳腺癌中基质金属蛋白酶-8启动子基因型的关联

The Association of Matrix Metalloproteinase-8 Promoter Genotypes in Breast Cancer.

作者信息

Hsiao Chieh-Lun, Liu Liang-Chih, Shih Tzu-Ching, Chuang Chin-Liang, Chen Guan-Liang, Wang Hwei-Chung, Pan Su-Yi, Shen Te-Chun, Tsai Chia-Wen, Chang Wen-Shin, Way Tzong-DER, Chung Jing-Gung, Bau DA-Tian

机构信息

Terry Fox Cancer Research Laboratory, Translational Medical Research Center, China Medical University Hospital, Taichung, Taiwan, R.O.C.

Ph.D. Program for Biotechnology Industry, China Medical University, Taichung, Taiwan, R.O.C.

出版信息

Anticancer Res. 2018 Apr;38(4):2181-2185. doi: 10.21873/anticanres.12459.

Abstract

BACKGROUND/AIM: The family of matrix metalloproteinases (MMPs) controls homeostasis of the extracellular matrix and their genetic polymorphisms may be associated with personal cancer susceptibility. The serum levels of MMP8 was reported to be higher in patients with breast cancer than in healthy individuals. In this study, we aimed to investigate the contribution of a polymorphism in the promoter region of MMP8 (-799C/T) and two nonsynonymous polymorphisms (Val436Ala and Lys460Thr) to breast cancer.

MATERIALS AND METHODS

MMP8 -799C/T, Val436Ala and Lys460Thr polymorphic genotypes were determined for 1,232 patients with breast cancer and 1,232 healthy controls by polymerase chain reaction-restriction fragment length polymorphism methodology.

RESULTS

The odds ratios (ORs) after adjusting for age, gender, smoking and alcohol drinking status for those carrying CT and TT genotypes at the MMP8 promoter C-799T were 1.03 (95% CI=0.88-1.23, p=0.7475) and 1.08 (95% CI=0.91-1.53, p=0.3561), respectively, compared to those carrying the wild-type CC genotype. The OR for the combined T-bearing genotypes were of a similar non-significant level (OR=1.05, 95% CI=0.90-1.26, p=0.5176). Supporting this finding, the adjusted OR for those carrying the T allele at MMP8 C-799T was 1.05 (95% CI=0.86-1.21, p=0.3797), compared to those carrying the wild-type C allele. There was also no significant association of MMP8 Lys460Thr with breast cancer. There was no polymorphic genotype at MMP8 Val436Ala found among any of the investigated individuals.

CONCLUSION

MMP8 -799C/T, Val436Ala and Lys460Thr polymorphisms may only play an indirect role in determining personal cancer susceptibility to breast cancer in Taiwan.

摘要

背景/目的:基质金属蛋白酶(MMPs)家族控制细胞外基质的稳态,其基因多态性可能与个体患癌易感性相关。据报道,乳腺癌患者血清中MMP8水平高于健康个体。在本研究中,我们旨在探讨MMP8启动子区域多态性(-799C/T)以及两个非同义多态性(Val436Ala和Lys460Thr)与乳腺癌的关系。

材料与方法

采用聚合酶链反应-限制性片段长度多态性方法,对1232例乳腺癌患者和1232例健康对照者进行MMP8 -799C/T、Val436Ala和Lys460Thr多态性基因型检测。

结果

在MMP8启动子C-799T位点,校正年龄、性别、吸烟和饮酒状况后,携带CT和TT基因型者的比值比(OR)分别为1.03(95%可信区间[CI]=0.88-1.23,p=0.7475)和1.08(95%CI=0.91-1.53,p=0.3561),与携带野生型CC基因型者相比。携带含T基因型的合并OR处于相似的无显著差异水平(OR=1.05,95%CI=0.90-1.26,p=0.5176)。支持这一发现的是,在MMP8 C-799T位点携带T等位基因者校正后的OR为1.05(95%CI=0.86-1.21,p=0.3797),与携带野生型C等位基因者相比。MMP8 Lys460Thr与乳腺癌也无显著关联。在所有被调查个体中均未发现MMP8 Val436Ala的多态性基因型。

结论

在台湾地区,MMP8 -799C/T、Val436Ala和Lys460Thr多态性可能仅在决定个体对乳腺癌的患癌易感性方面起间接作用。

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