| Abstract: | Background/Aim: Metalloproteinases (MMPs) are
a family of multifunctional proteins reported to be
overexpressed in several types of cancers. However, the
contribution of MMP8 genotype to oral cancer has not been
elucidated. In this study, we focused on the contribution of
polymorphisms in the promoter region of MMP-8 (C-799T)
and two non-synonymous polymorphisms (Val436Ala and
Lys460Thr) to Taiwanese oral cancer. Materials and Methods:
In this case-control study, MMP-8 genotype, was examined
among 788 patients with oral cancer and 956 gender- and
age-matched healthy controls regarding its potential to
determine oral cancer risk. Results: The distributions of
MMP-8 C-799T, Val436Ala and Lys460Thr genotypes were
not different between the oral cancer and non-cancer control
groups. We also analyzed the allelic frequency distributions
and no significant difference was found. As for geneenvironment
interaction analysis, there was an increased risk
for smokers, alcohol drinkers or betel quid chewers with
variant MMP-8 C-799T or Val436Ala genotypes. Conclusion:
Our findings suggest that the polymorphisms at MMP-8 C-
799T or Val436Ala may not play a major role in mediating
personal risk of oral cancer; however, the detailed
mechanisms require further investigation.
Oral cancer is the eighth most commonly diagnosed cancer
worldwide and has the highest male incidence density in
Taiwan (1-3). There is regional variation in trends of oral
cancer around the world, depending on the etiology and the
risk factors involved. According to the government annual
report, oral cancer is the fourth cause of cancer-related death
among males in Taiwan and has been reported to be closely
associated with tobacco, alcohol and betel nut consumption
habits (4-7). In the past years, genomic biomarkers for oral
cancer in Taiwan have been revealed (8-14) and further
cellular etiological investigations and the interactions among
the genetic and lifestyle factors will contribute to
personalized cancer early detection and therapy.
Matrix metalloproteinases (MMPs), also known as
matrixins, are a family of calcium-dependent zinc-containing
endopeptidases that play a key role in extracellular matrix
homeostasis controlling the degradation of the components
of connective tissue matrices (15, 16). In carcinogenesis,
MMPs and their inhibitors are also related to the regulation
of oral cancer invasion and metastasis (17-20). The
imbalance of these MMPs and their interactions with specific
inhibitors, e.g. the tissue inhibitors of metalloproteinases
(TIMPs), may contribute to the initiation and progression of
cancer (16, 17, 21). MMP-8, originally known as neutrophil
collagenase, is expressed in not only neutrophils but also
epithelial cells, fibroblasts, macrophages and endothelial
cells (22-24). In recent years, mounting evidence showed
that MMP-8 was capable to conduct cancer- and metastasissuppressive
activities. Firstly, knockout of MMP induced a
dramatic increase in the incidence of carcinogen-induced
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