| RE:
LACK OF ASSOCIATION BETWEEN MATRIX METALLOPROTEINASE-1 (MMP-1) PROMOTER
POLYMORPHISM AND RISK OF RENAL CELL CARCINOMA
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MICHELLY F. PICCOLI,
MARCIA FIGUEIRA, CASSIO ANDREONI, JULIO T. MARUMO, NESTOR SCHOR, MARIA
H. BELLINI
Section of
Nephrology (MFP, MF, NS, MHB) and Section of Urology (CA), Federal University
of Sao Paulo, UNIFESP, and Institute of Energetic and Nuclear Research
(JTM, MHB), Sao Paulo, SP, Brazil
Int
Braz J Urol, 33: 622-629, 2007
To the Editor:
Matrix
Metalloproteinases (MMPs) are a family of extracellular matrix degradative
enzymes physiologically involved in tissue development and remodeling.
Now they are being widely studied for their potential role in the progression
and metastasis of many tumors (1).
Indeed degradation of extracellular matrix
is one of the crucial and early steps in many carcinomas. The role of
the huge family of these enzymes and their inhibitors in cancer cells
invasion, metastasis (2), proliferation and angiogenesis (3) is probably
much more complex than it seems and still needs to be clarified.
On these basis, many authors paid attention
to the overexpression of MMPs enzymes in renal cell carcinoma (RCC). Overexpression
of MMP2 and MMP9 has been described in association with poor prognosis
of patients with RCC (4-6). Overexpression of MMP1, MMP3, MMP7, MMP11,
MMP12 and MMP14 has been described in tissue of RCC (7,8). More recently,
a strong relation between MMP10 expression and stage and grade of RCC
has been demonstrated (9).
These growing evidences of MMPs role in
RCC pathogenesis is the strong rationale to plan genetic investigation
to assess not only the phenotype but the genotype modification that stand
behind RCC development and progression.
The genetic population based studies are
mainly aimed at identifying groups at a higher risk of developing a cancer
or at a higher risk of having a cancer with a worse prognosis. The case
control population based researches are often biased by not controllable
factors especially when the sample size is limited. Moreover, the results
of genetic studies are complicated by the wide heterogeneity between different
ethnic groups. To draw any conclusion from genetic statistics we need
wide sample sizes, from different regions to compare the results of different
ethnic groups.
The efforts and the costs of such studies
are worthy. Indeed the future possibility of identifying a high-risk group
for RCC by a simple test for genetic polymorphism will lead to an early
diagnosis of cancer in these patients. The people bearing the high-risk
alleles will take advantage of a strict clinical surveillance for example
with periodic ultrasound scan.
Even if the results of the authors do not
allow identifying an increased risk of RCC for the MMP1 promoter polymorphism
in Brazil, they are still important. If further data support these results,
the geneticists will have to search for more loci in order to identify
one or more gene polymorphisms responsible for increased risk of RCC in
Brazil. If further data do not support the result of the aforementioned
study, the geneticists will have to plan a wider population based study
to answer to the question about the MMP1 promoter polymorphism and the
risk of RCC in Brazil.
REFERENCES
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Matrix metalloproteinases and their inhibitors in plasma and tumor tissueof
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expression of metalloproteinase 9 correlates with poor prognostic variables
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8. Sumi T, Nakatani T, Yoshida H, Hyun Y, Yasui T, Matsumoto Y, et al.:
Expression of matrix metalloproteinase-7 and 2 in human renal cell carcinoma.
Oncol Rep. 2003; 10: 567-70.
9. Miyata Y, Iwata T, Maruta S, Kanda S, Nishikido M, Koga S, et al.:
Expression of matrix metalloproteinase-10 in renal cell carcinoma and
its prognostic role. Eur Urol. 2007; 52: 791-7.
Dr. Andrea Zitella
Dr. Paolo Gontero
Ricercatore in Urologia Università di Torino
Ospedale Molinette, Torino, Italy
E-mail: paolo.gontero@unito.it
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