Our findings provide evidence that the T allele of EZH2 rs887569 may be associated with the lower risk of bladder cancer development, especially among non-smokers.

Background/Aim: In literature, few studies have examined the diagnostic or prognostic potential of matrix metalloproteinases (MMP) in pterygium, whose formation and progression are closely related to imbalance in the extracellular microenvironment. In this study, we investigated the contribution of MMP7 promoter (A-181G and C-153T) polymorphic genotypes to pterygium risk. Materials and Methods: A total of 134 cases and 268 controls were collected and their MMP7 genotypes at A-181G and C-153T were examined by polymerase chain reaction-restriction fragment length polymorphism methodology. Results: The AA, AG and GG genotypes at MMP7 promoter A-181G were nonsignificantly differentially distributed between the two groups at 85.8, 11.2 and 3.0%, respectively, in pterygium cases and 88.4, 9.7 and 1.9% in controls, respectively (p for trend=0.6822). There was no polymorphic genotype for MMP7 C-153T among our Taiwanese cohort. Conclusion: A-181G and C-153T genotypes at MMP7 do not have a direct role in determining Taiwanese susceptibility to pterygium. Pterygium is a disease presenting an abnormal wing-shaped outgrowth of fibrovascular conjunctival tissues invading the clear cornea. The etiology of pterygium is still largely unclear. The incidence of pterygium is epidemiologically due to several factors, such as overexposure to sunshine, UV light, heat, dust, and other particles in the atmosphere (1-3). In the past two decades, mounting evidence has supported the concept that variations in our genome play a critical role in the determination of the etiology and development of pterygium (4-11). Many theories for pterygium have been proposed, such as imbalances in immunological mechanisms, growth factors, cytokines, apoptosis, angiogenesis (12-15), and most interestingly but complicatedly, an imbalance in the extracellular microenvironment and the involvement of matrix metalloproteinases (MMPs) (16-19). MMPs are a group of zinc-binding endopeptidases responsible for regulating the components of the extracellular matrix microenvironment (20). The activation of MMPs generally takes place in the extracellular space, and interacts with various other proteases, teaming up to regulate the behaviors of cancer cells including viability, cell differentiation, programmed cell death, angiogenesis, immune surveillance, invasiveness and migration capacity (21, 22). The smallest MMP member, MMP7 (matrilysin), is responsible for the metabolism of a broad spectrum of substrates including fibronectin, vitronectin, elastin, collagen IV, aggrecan, and proteoglycans (23). In addition, MMP7 is involved in inflammatory responses via its capacity to promote cell-surface processing of cytokines such as tumor necrosis factor a (24). MMP7 activation was first proposed to be involved in the pathogenesis of pterygium as early as 2001 by Girolamo and colleagues (25). In their analysis of cultured pterygial and conjunctival tissues from eight pterygium cases at Wales hospital in Sydney, basal and activated MMP7 levels were 1.4-and 2.7-fold higher, resp...

Background/Aim: The breakage of matrix metalloproteinases (MMPs) has been reported to be one of the mechanisms required for tumor invasion, and the expression of MMP-7 in serum is correlated with poor prognosis of urinary bladder cancer patients. However, the role of the MMP-7 genotypes has been seldom examined among bladder cancer patients. Therefore, this study aimed at examining the promoter polymorphic MMP-7 genotypes A-181G and C-153T among Taiwanese bladder cancer patients and evaluate the contribution of the genotypic variants of MMP-7 to bladder cancer risk in Taiwan. Materials and Methods: Three hundred and seventy-five bladder cancer patients and the same number of gender-and age-matched healthy controls were genotyped for A-181G and C-153T in the promoter of MMP-7 via polymerase chain reaction-restriction fragment length polymorphism methodology. Results: The frequencies of AA, AG and GG at A-181G of the promoter of MMP-7 were 89.1, 8.8 and 2.1% in the bladder cancer patient group and 87.5, 10.9 and 1.6% in the matched healthy control group, respectively (p for trend=0.5475). There was no polymorphic genotype for MMP-7 C-153T among the Taiwanese population. The comparisons in allelic frequency distribution also support the findings that the G allele may not be the determinant allele for bladder cancer in Taiwan. In addition, the results showed that there is no significant association of the bladder risk with the MMP-7 A-181G genotype, even after adjustment for the possible confounding factors. Furthermore, there is no interaction of the genotypes of MMP-7 with age, gender, smoking and alcohol consumption on bladder cancer risk. Conclusion: The results of this study suggest that the two MMP-7 polymorphisms,-A-181G and C-153T, do not play a major role in determining personal susceptibility to bladder cancer in Taiwan. Bladder cancer is the 2nd most common urological malignancy worldwide, contributing to about 5% of cancer deaths and is estimated to cost four million dollars each year (1). According to the statistical data provided by the International Agency for Research on Cancer, there were an estimated 429,800 new cases of bladder cancer and 165,100 deaths in 2012 worldwide, and males are four times more likely to develop the disease than females (1, 2). In Taiwan, bladder cancer ranks seventh in incidence and mortality among the common types of cancer (3, 4). Tumorigenesis of bladder cancer is a complex, multistep and multifactorial process being the result of interactions of lifestyle, environmental and genetic factors (3-9). The matrix metalloproteinases (MMPs, matrixins) are a family of endopeptidases that have been reported to play a key role in maintaining the homeostasis of extracellular matrix (ECM) components and the processes of inflammation, carcinogenesis and cancer cell migration (10, 11). Since the 1045 This article is freely accessible online.

Our findings suggest that the polymorphic genotypes at MMP-1 promoter -1607 may play a major role in determining personal cancer susceptibility for prostate cancer in Taiwan.

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