title: Matrix Metalloproteinase-1 Genotype Contributes to the Risk of Non-solid Tumor in Childhood Leukemia.
abstract: Up-regulation of metalloproteinase (MMPs) proteins have been shown in various types of solid cancers and the genotype of MMP1 has been associated with the risk of solid cancers. However, the contribution of MMP1 genotype to leukemia has never been investigated to our knowledge. Therefore, in this study we aimed to evaluate the contribution of the genotypic variants in the promoter region of MMP1 to childhood acute lymphoblastic leukemia (ALL) risk in Taiwan.
  
  
  
  In this case-control study, 266 patients with childhood ALL and 266 non-cancer controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism methodology.
  
  
  
  The distribution of 2G/2G, 1G/2G and 1G/1G for MMP1 promoter rs1799750 genotype was 49.2%, 39.5% and 11.3% in the childhood ALL group and 36.8%, 43.6% and 19.5% in the non-cancer control group, respectively (p for trend=0.0046), significantly differentially distributed between childhood ALL and control groups. The carrier comparisons in dominant and recessive models also support the findings that 1G appears to be the protective allele in childhood ALL. In genotype and gender interaction analysis, it was found that boys carrying the MMP1 rs1799750 1G/2G or 1G/1G genotypes had lower odds ratios(ORs) of 0.68 and 0.43 [95% confidence intervals (CI)=0.47-0.98 and 0.26-0.73, p=0.0395 and 0.0013, respectively] for childhood ALL than those carrying the 2G/2G genotype. Analysis of genotype inaction with age of onset age showed those aged less than 3.5 years at onset carrying the 1G/2G or 1G/1G genotypes had lower ORs (0.0183 and 0.0004, respectively) for childhood ALL, but there was no such difference for those having an age at onset of 3.5 years or more.
  
  
  
  Our results indicate that the MMP1 rs1799750 1G allele is a protective biomarker for childhood ALL.
authors: Department of Pediatrics, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan, R.O.C.
authors: Jen-Sheng
authors: JS
authors: Pei
authors: Department of Pediatrics, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan, R.O.C.
authors: Pei-Chen
authors: PC
authors: Hsu
authors: Department of Anesthesiology, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors: An-Kuo
authors: AK
authors: Chou
authors: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors: Chia-Wen
authors: CW
authors: Tsai
authors: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.
authors: Wen-Shin
authors: WS
authors: Chang
authors: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C.|Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.
authors: Chieh-Lun
authors: CL
authors: Hsiao
authors: Department of Family Medicine, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan, R.O.C.
authors: Yuan-Nian
authors: YN
authors: Hsu
authors: Department of Physical Medicine and Rehabilitation, Taoyuan General Hospital, Ministry of Health and Welfare, Taoyuan, Taiwan, R.O.C.
authors: Shun-Ping
authors: SP
authors: Cheng
authors: Terry Fox Cancer Research Laboratory, China Medical University Hospital, Taichung, Taiwan, R.O.C. datian@mail.cmuh.org.tw artbau2@gmail.com.|Graduate Institute of Clinical Medical Science, China Medical University, Taichung, Taiwan, R.O.C.|Department of Bioinformatics and Medical Engineering, Asia University, Taichung, Taiwan, R.O.C.
authors: DA-Tian
authors: DT
authors: Bau
mesh_terms: D016022:Case-Control Studies; D002675:Child, Preschool; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000235:genetics*; D016017:Odds Ratio; D054198:Precursor Cell Lymphoblastic Leukemia-Lymphoma / Q000453:epidemiology / Q000235:genetics*; D011401:Promoter Regions, Genetic; D012307:Risk Factors; D013624:Taiwan / Q000453:epidemiology
chemical_list: C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1
keywords: Childhood leukemia; MMP1; Taiwan; genotype; polymorphism