IGF-1 IGFBP-3 [14] [15] [16] [17] [18] [19] [14] [15] [16] [17] [18] [19] N1 is the number of cases, N2 is the number of controls; ---, not available. lowest as the principal effect measure in our meta-analy- sis. The cutoff values for these categories were based on control groups, which better represented the distribution of IGF-I and IGFBP-3 in the general population. The adjusted ORs and their 95% confidence intervals were abstracted directly from the publications. We also used the weighted mean difference (WMD) to compare circu- lating levels of IGF-1 and IGFBP-3 of lung cancer cases with that of their controls. Heterogeneity assumption was checked by the chi-square- based Q test [20]. A P value > 0.10 for the Q test indicates a lack of heterogeneity among studies, so the pooled OR estimate of the each study was calculated by the fixed- effects model (the Mantel-Haenszel method) [21]. Other- wise, the random- effects model (the DerSimonian and N1 93 230 159 194 200 167 93 230 159 194 200 167 --- 123 158 124 137.2 --- --- 1793 30700 2780 2228 --- OR (95% CI) % Weight 0.54 ( 0.14, 2.07)7.6 0.86 ( 0.47, 1.57)23.3 0.64 ( 0.31, 1.33)27.1 1.74 ( 1.08, 2.81)9.4 0.76 ( 0.39, 1.49)23.3 1.21 ( 0.62, 2.35)9.4 0.87 ( 0.60, 1.13)100.0 --- 46.43 56 54 52.3 --- --- 487.43 8200 860 650 --- ] r [og 0 o l 2 1 -1 -2 Journal of Experimental & Clinical Cancer Research 2009, 28:89 http://www.jeccr.com/content/28/1/89 Table 2: Studies reporting IGF-I and IGFBP-3 levels in lung cancer patients and their controls Serum factors References Cases Cases Mean(ng/ml) SD(ng/ml) Mean(ng/ml) SD(ng/ml) 0 .2 .6 .8 .4 s.e. of: log[or] lFFuuingngunceralenp2cloert for publication bias in the analysis of IGF-I and Funnel plot for publication bias in the analysis of IGF- I and lung cancer. Each circle indicates the logarithm of the odds ratio of lung cancer comparing the subjects in the high- est category with the lowest (vertical axis) and the standard error of logarithm of odds ratio in each study. The line in the centre indicates the summary diagnostic odds ratio. Page 3 of 6 (page number not for citation purposes) N2 186 740 297 9351 400 498 186 740 297 9351 400 498 --- 127 153 126 145.5 --- --- 1863 29400 2990 2369 --- --- 41.62 54 57 52 --- --- 458.76 7900 810 640 --- Laird method) was used [22]. An estimate of potential publication bias was carried out by the funnel plot, in which the standard error of log (OR) of each study was plotted against its log (OR). An asymmetric plot suggests a possible publication bias. Funnel plot asymmetry was assessed by the method of Egger's linear regression test, a linear regression approach to measure funnel plot asym- metry on the natural logarithm scale of the OR. The signif- icance of the intercept was determined by the t test suggested by Egger (P < 0.05 was considered representa- tive of statistically significant publication bias) [23]. Stata statistical package version 10.0(Stata Corporation, Col- Begg's funnel plot with pseudo 95% confidence limits Study Lukanova 2001 London 2002 Spitz 2002 Waikai 2002 Ahn 2006 Morris 2006 Overall -3 0 OR 1 3 lFGuinrgagupcrhaeicn1creerpresentation of the meta-analysis for IGF-I and Graphic representation of the meta-analysis for IGF-I and lung cancer. The ORs and their 95% confidence inter- vals in the original studies are shown..