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Genetic polymorphisms in matrix metalloproteinases ( MMPs ) and tissue inhibitors of MPs ( TIMPs ), and bladder cancer susceptibility
Author(s) -
Wieczorek Edyta,
Reszka Edyta,
Jablonowski Zbigniew,
Jablonska Ewa,
Beata Krol Magdalena,
Grzegorczyk Adam,
Gromadzinska Jolanta,
Sosnowski Marek,
Wasowicz Wojciech
Publication year - 2013
Publication title -
bju international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.773
H-Index - 148
eISSN - 1464-410X
pISSN - 1464-4096
DOI - 10.1111/bju.12230
Subject(s) - genotype , medicine , odds ratio , matrix metalloproteinase , bladder cancer , allele , tissue inhibitor of metalloproteinase , confidence interval , gastroenterology , immunology , oncology , pathology , genetics , cancer , gene , biology
Objectives To elucidate genetic polymorphisms of the matrix metalloproteinases ( MMPs ) MMP 1 (rs1799750) , MMP 2 (rs243865) , MMP 9 (rs3918242) , MMP 12 (rs2276109) and tissue inhibitors of MMPs ( TIMPs ) TIMP 1 (rs2070584) and TIMP 3 (rs9619311) genes that may be involved in susceptibility to bladder cancer ( BC ).Patients and Methods We enrolled 241 patients with BC and 199 controls. Genomic DNA samples were extracted from peripheral blood and polymorphisms were analysed by high‐resolution melting analysis and by real‐time polymerase chain reaction using T aq M an fluorescent probes.Results Of the six evaluated polymorphisms of MMPs and TIMPs , only one was found to be associated with BC risk. There was a significant difference for MMP 1 (rs1799750) 2 G /1 G +1 G /1 G genotype (odds ratio [ OR ] 0.62, 95% confidence interval [ CI ] 0.39–0.98; P = 0.042). Additionally, there was a joint effect of this genotype on BC risk among ‘ever smokers’ ( OR 0.51, 95% CI 0.28–0.89; P = 0.019), but not in ‘never smokers’. The combined genotype MMP 2 –1306 C / T (rs243865) allele T with MMP 9 –1562 C / T (rs3918242) allele T was found to increase BC risk ( OR 2.00, 95% CI 1.10–3.62; P = 0.022).Conclusions Our results suggest that genetic variations in five polymorphisms of MMPs and TIMPs are not associated with a high risk of BC . Only MMP 1 polymorphism may be related to the risk of BC , notably in ‘ever smokers’. Our study suggests that the effects of polymorphisms of MMPs and TIMPs on BC risk deserve further investigation.