Higher risk of matrix metalloproteinase (MMP-2, 7, 9) and tissue inhibitor of metalloproteinase (TIMP-2) genetic variants to gallbladder cancer

• Published in: Liver international 2012-09, Vol.32 (8), p.1278-1286
• Main Authors: Sharma, Kiran L., Misra, Sanjeev, Kumar, Ashok, Mittal, Balraj
• Format: Article
• Language: English
• Subjects: Adult; Cancer; Collagen; Extracellular matrix; Female; Gallbladder; gallbladder cancer; Gallbladder Neoplasms - epidemiology; Gallbladder Neoplasms - genetics; Gelatinase A; Gelatinase B; Gene polymorphism; Genetic Predisposition to Disease - epidemiology; Genetic Predisposition to Disease - genetics; genetic variants; Genetic Variation; Genotyping; Guanylate cyclase; Haplotypes; Humans; India - epidemiology; Liver; Logistic Models; Male; Matrilysin; Matrix metalloproteinase; Matrix Metalloproteinase 2 - genetics; Matrix Metalloproteinase 7 - genetics; Matrix Metalloproteinase 9 - chemistry; Matrix Metalloproteinase 9 - genetics; matrix metalloproteinases; Middle Aged; Models, Chemical; Multivariate Analysis; Polymerase chain reaction; Polymorphism, Genetic; Restriction fragment length polymorphism; Risk Factors; Statistical analysis; Tissue inhibitor of metalloproteinase 2; Tissue Inhibitor of Metalloproteinase-2 - genetics; Tissue inhibitor of metalloproteinases
• ISSN: 1478-3223; 1478-3231
• DOI: 10.1111/j.1478-3231.2012.02822.x

Background Matrix metalloproteinase belong to family of pericellular collagenases which degrade extracellular matrix (ECM), and is involved in the modulation and susceptibility of various cancers. Methodology The present study included 410 gallbladder (GBC) cases and 230 healthy controls from North India. Study examined the associations of polymorphisms of MMP‐2c.735C>T (rs2285053), MMP‐2c.1306 C>T (rs243865), MMP7c.181A>G (rs11568818), MMP‐9p.R279Q (rs17556) MMP‐9p.P574R (rs2250889), MMP‐9 p.R668Q (rs17577) and TIMP2c.418 G>C (rs8179090) to GBC susceptibility. Genotyping was carried out by PCR‐RFLP. Statistical analysis was performed by using SPSS ver16. Results The MMP‐2 c.735 [CT+TT], MMP‐2c.1306 [CT+TT], MMP7 c.181 [AG+GG] and MMP‐9 p.668 [RQ+QQ],TIMP2c.418 [GG+GC] genotypes were significantly associated with increased risk of GBC (P = 0.01; [OR]1.87, P = 0.02; [OR] 1.68, P = 0.02; [OR]=1.61, P = 0.002; [OR]=1.91,P = 0.01; [OR]=1.78 and (P = 0.03; [OR]=1.68; P = 0.01; [OR]=1.78 respectively). Haplotypes [C‐735‐T‐1306] and [T‐1306‐C‐735] of MMP‐2 (P = T), MMP‐9 p.R668Q and TIMP2c.418G>C variants with GBC susceptibility. Conclusion This study suggests that genetic variants in MMP‐2,7,9 and TIMP‐2genes are associated with higher susceptibility of gallbladder cancer.