Laboratory of Human Carcinogenesis, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-4258, USA.
Int J Cancer. 2012 Dec 1;131(11):2710-6. doi: 10.1002/ijc.27573. Epub 2012 Apr 27.
Conflicting reports exist regarding the contribution of SNP309 in MDM2 to cancer risk. Recently, SNP285 was shown to act as an antagonist to SNP309 by overriding the effect of SNP309 on SP1-mediated transcription. Moreover, SNP285 modified the relationship between SNP309 and risk of breast, ovarian and endometrial cancer. We assessed whether SNP285 confounded the effect of SNP309 in lung cancer in a cohort of 720 controls and 556 cases. Our cohort included both Caucasians and African Americans. Neither SNP309 nor SNP285 was associated with lung cancer risk or survival. In addition, removal of individuals who carried the variant C allele of SNP285 did not modify the association between SNP309 with either lung cancer risk or survival. Although an effect of SNP285 has been demonstrated in breast, ovarian and endometrial cancer, our findings do not support a role for this SNP in lung cancer and raise the possibility that the effect of SNP285 is restricted to cancers in women.
关于 SNP309 在 MDM2 中对癌症风险的贡献，存在相互矛盾的报告。最近的研究表明，SNP285 可以通过覆盖 SNP309 对 SP1 介导的转录的影响，充当 SNP309 的拮抗剂。此外，SNP285 改变了 SNP309 与乳腺癌、卵巢癌和子宫内膜癌风险之间的关系。我们评估了 SNP285 是否会在一个由 720 名对照和 556 名病例组成的队列中混淆 SNP309 在肺癌中的作用。我们的队列包括白种人和非裔美国人。SNP309 和 SNP285 均与肺癌风险或生存无关。此外，去除携带 SNP285 变体 C 等位基因的个体并没有改变 SNP309 与肺癌风险或生存之间的关联。尽管 SNP285 的作用已在乳腺癌、卵巢癌和子宫内膜癌中得到证实，但我们的研究结果并不支持该 SNP 在肺癌中的作用，并提出 SNP285 的作用可能仅限于女性癌症的可能性。
