Polymorphisms of matrix metalloproteinases 1, 2, 3 and 9 and susceptibility to lung, breast and colorectal cancer in over 30,000 subjects.

A variety of susceptibility genes have been associated with cancer but definitive conclusions have been difficult to draw partly hampered by the small number of subjects in each study. We undertook a comprehensive genetic meta-analysis of all matrix metalloproteinase (MMP) genes investigated using an allelic-association case-control model in the 3 major cancers of lung, breast and colorectal cancer. Electronic databases were searched until and including July 2008 for any MMP genetic association study in lung, breast and colorectal cancer. Odds ratio (OR) and 95% confidence intervals (CI) were determined for each gene disease association using fixed and random effect models. Twenty-five studies addressing 5 polymorphisms in 4 genes were analyzed among 30,651 individuals (15,328 cases and 15,253 controls). The MMP-1 nt-1607 polymorphism was significantly associated with colorectal cancer in both the dominant (OR, 1.66; 95% CI, 1.14-2.42; p = 0.008) and recessive (OR, 1.59; 95% CI, 1.15-2.20; p = 0.005) models. MMP-2(1306C-->T) (OR, 0.53; 95% CI, 0.40-0.72; p < 0.0001) and 735(C-->T) (OR, 0.65; 95% CI, 0.53-0.79; p < 0.0001) were significantly associated with protection against lung cancer. No association was found with the MMP 1, 2, 3 or 9 polymorphisms with breast cancer, MMP-1, 3 or 9 with lung cancer or MMP-2, 3 or 9 with colorectal cancer. There may be a genetic influence in the development of colorectal and lung cancer. Subjects with the MMP-1 nt-1607 polymorphism have an increased association with colorectal cancer. Those homozygous for either the MMP-2/1306T or 735T allele may be at reduced risk of lung cancer, although the evidence base is small. 2009 UICC