AbstractBACKGROUNDCleft lip with or without cleft palate (CL/P) is one of the most common craniofacial malformations, with a complex and multifactorial etiology. Because of the genetic heterogeneity of facial clefts, the aim of this study was to investigate the contribution of previously reported candidate genes and chromosomal loci to the risk of CL/P in the Polish population.METHODSWe performed an analysis of 18 polymorphisms of FOXE1, IRF6, MSX1, PAX9, TBX10, FGF10, FGFR1, TGFα, TGFβ3, SUMO1, and the chromosomal region 8q24 in a group of 175 patients with CL/P and a properly matched control group.RESULTSHighly significant results were observed for the IRF6 rs642961 variant and the 8q24 region's rs987525 (odds ratio [OR]AG+AAvsGG, 1.635; 95% confidence interval [CI], 1.153–2.319; p = 0.005; and ORAC+AAvsCC, 1.962; 95% CI, 1.382–2.785; p = 1.4 × 10−4, respectively). For rs987525, the results were also significant after correction for multiple comparisons. Borderline association with an increased risk of CL/P was also identified for the SUMO1 locus (rs2350350; ORCGvsGG, 1.580; 95% CI, 1.056–2.363; p = 0.025).CONCLUSIONSOur findings confirmed that genetic variants of IRF6 and the polymorphism located in the 8q24 gene desert are strongly involved in the etiology of facial clefts in the Polish population sample. Birth Defects Research (Part A), 2010. © 2010 Wiley‐Liss, Inc.