Although genetic variations in cell-cycle control genes have been previously linked to cancer risk, no study has specifically evaluated the role of these gene variants in endometrial carcinogenesis. Using data from the Shanghai Endometrial Cancer Study, a population-based case-control study with 1,199 cases and 1,212 age-matched controls (1997-2003), the authors carried out a systematic evaluation of the association of cell-cycle control genes with endometrial cancer risk. Sixty-five tagging or potentially functional single nucleotide polymorphisms in the CCNB1, CCND1, CCNE1, CDK2, CDK4, CDK6, CDKN1A, CDKN1B, and CDKN2A genes were genotyped and evaluated. Three single nucleotide polymorphisms in the CDKN1B gene (rs11055027, rs3759216, and rs34330) were related to endometrial cancer risk, although only the association with rs34330 remained statistically significant after adjustment for multiple comparisons. The odds ratios for rs34330 were 1.33 (95% confidence interval (CI): 1.06, 1.66) and 1.51 (95% CI: 1.16, 1.94) for the CT and TT genotypes, respectively, compared with the CC genotype. In vitro luciferase reporter assays showed that the minor allele (A) in rs3759216, which was associated with decreased endometrial cancer risk (odds ratio = 0.73, 95% CI: 0.56, 0.94) without adjustment for multiple comparisons, significantly increased promoter activity. These findings suggest that polymorphisms of the CDKN1B gene may play a role in endometrial carcinogenesis.