title: The functional polymorphism in the matrix metalloproteinase-7 promoter increases susceptibility to esophageal squamous cell carcinoma, gastric cardiac adenocarcinoma and non-small cell lung carcinoma.
abstract: An A to G transition at the 181 base pair position upstream of the transcription initiation site of the matrix metalloproteinase-7 (MMP-7) gene (-181A/G) may modify the development and progression of some diseases via influencing the transcription activity of the promoter. To assess the effects of the functional single nucleotide polymorphism on cancer susceptibility and progression, the MMP-7 -181A/G genotypes were determined by polymerase chain reaction-restriction fragment length polymorphism analysis among 258 patients with esophageal squamous cell carcinoma (ESCC), 201 patients with gastric cardiac carcinoma (GCA), 243 patients with non-small cell lung carcinoma (NSCLC) and 350 healthy individuals without cancer. The result showed that the frequency of the -181G allele in ESCC, GCA and NSCLC patients was significantly higher than that in healthy controls (P = 0.019, 0.023 and 0.004, respectively). Compared with the A/A genotype, genotypes with the -181G allele (A/G + G/G) significantly increased susceptibility to all three tumors, with adjusted odds ratio of 1.83 (95% CI = 1.12-2.99) for ESCC, 1.96 (95% CI = 1.17-3.29) for GCA and 2.00 (95% CI = 1.23-3.24) for NSCLC. Stratification analysis showed that smoking did not significantly influence the association between the MMP-7-181A/G and GCA or NSCLC, while the -181G allele only significantly increased susceptibility to ESCC among smokers. In addition, association between the -181G allele and susceptibility to ESCC and GCA showed significance only among individuals with family history of upper gastrointestinal cancer. The correlation of the MMP-7-181A/G polymorphism with potential of lymphatic metastasis was not observed in all three tumors. The study suggested that, the MMP-7-181A/G polymorphism might be a candidate marker for predicting individuals who are at higher risk to certain tumors but might not be used to predict potential of lymphatic metastasis in ESCC, GCA and NSCLC.
authors.affiliation: Hebei Cancer Institute, Hebei Medical University, Jiankanglu 12, Shijiazhuang 050011, Hebei Province, China. Jianhuizh@hotmail.com
authors.forename: Jianhui
authors.initials: J
authors.lastname: Zhang
authors.forename: Xia
authors.initials: X
authors.lastname: Jin
authors.forename: Shumei
authors.initials: S
authors.lastname: Fang
authors.forename: Rui
authors.initials: R
authors.lastname: Wang
authors.forename: Yan
authors.initials: Y
authors.lastname: Li
authors.forename: Na
authors.initials: N
authors.lastname: Wang
authors.forename: Wei
authors.initials: W
authors.lastname: Guo
authors.forename: Yimin
authors.initials: Y
authors.lastname: Wang
authors.forename: Denggui
authors.initials: D
authors.lastname: Wen
authors.forename: Lizhen
authors.initials: L
authors.lastname: Wei
authors.forename: Zhiming
authors.initials: Z
authors.lastname: Dong
authors.forename: Gang
authors.initials: G
authors.lastname: Kuang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D002294:Carcinoma, Squamous Cell / Q000235:genetics; D004938:Esophageal Neoplasms / Q000235:genetics; D020022:Genetic Predisposition to Disease; D006338:Heart Neoplasms / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics*; D020783:Matrix Metalloproteinase 7 / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic; D013274:Stomach Neoplasms / Q000235:genetics
chemical_list: D020783:Matrix Metalloproteinase 7