BMC Cancer 2007, 7:187 http://www.biomedcentral.com/1471-2407/7/187 Table 4: Univariate analysis of predictive factors OSCC Controls Age <45 45 Gender Male Female 1Ga - + 2Gb - + 29 141 107 63 77 93 14 156 52 112 104 60 64 100 29 135 p 0.002 1.000 0.294 0.016 OR (95% CI) 2.26 (1.35–3.79) 0.98 (0.63–1.53) 1.29 (0.84–2.00) 2.39 (1.21–4.72) a: 1G- denotes 2G/2G, and 1G+ denotes 1G/1G or 1G/2G. b: 2G- denotes 1G/1G, and 2G+ denotes 2G/2G or 1G/2G. Data were analyzed by Fisher's exact test. The odds ratio and 95% CI were calculated. anism of the elevated risk of OSCC as related to the 2G allele of MMP-1 promoter includes genetic instability, which is accompanied by the cell cycle activation caused by a sequence of events led by increased MMP-1 enzyme activity, i.e. activation of tissue disruption, reconstruction and resultant release of ECM binding growth factors. The relationship between MMP-1 promoter polymorphism and risk of OSCC has been investigated by Lin et al. in a group of 121 cases [22] and by Cao et al. in a group of 96 cases [23] and by Vairaktaris et al. in a group of 156 cases [24]. Although both Lin et al. and Cao et al.reported an elevation of OSCC risk correlated with the MMP-1 2G allele, further studies were needed to reach a conclusion mainly because the numbers of cases in the previous stud- ies were relatively small, and there were differences between these reports in background analyses on correla- tion with environmental risk factors, such as smoking and areca use. In this study, significant correlations were found between the presence of the MMP-1 promoter 2G allele and increased OSCC risk among 170 Japanese OSCC patients. These results are consistent with existing reports on malignant neoplasms in general. It is notable that a new finding on the molecular function of MMP-1 in the onset of OSCC was obtained from the characteristic pattern of the MMP-1 promoter genotype distribution in younger patients. Interestingly, Vairaktaris et al. reported an increased risk of oral cancer with MMP-1 1G/2G polymorphism [24]. The discrepancy of the results of the Chinese studies and our report on one hand and the European (German and Greek) study on the other hand may be explained by the diverse ethnic background of the different studied popu- lations. Another point of difference is the fact that their patient sample included patients with positive family his- tory of thrombophilia. e g A 1G/1G 1G/2G 2G/2G bFAeiggtewudreiestnr1itbhuetiaognesofotfh2e0MaMndP-810gyeenaortsypes in 170 OSCC cases Age distribution of the MMP-1 genotypes in 170 OSCC cases between the ages of 20 and 80 years. The frequency of the 1G/1G genotype is notably low. Note the clear reduction of the 1G/1G and 1G/2G genotype distribu- tions in individuals under the ages of 45 and 35 years, respec- tively. The observed bias of the average age by the MMP-1 pro- moter genotype among the 170 OSCC cases of this study suggested an influence of the MMP-1 promoter 2G allele on the age of OSCC onset. The scatter plot of age on the MMP-1 promoter genotypes also revealed disappearance of the 1G/1G-genotype distribution among the OSCC cases under 45 years old. In agreement with this observa- tion, the ROC analysis suggested that the age of 45 years is the borderline age above which a change occurs in the incidence of OSCC. Although the specific reasons for these results have not been clarified, they suggest that some kind of biological conditions related to carcinogen- esis have initiated around the age of 45. Carcinogenesis is caused by synergistic effects of various factors [25,26]. The multivariate logistic regression analysis showed that aging Page 5 of 9 (page number not for citation purposes)