Department of Radiation Medicine, Georgetown University School of Medicine, Washington, DC, USA.
Cancer Epidemiol. 2012 Oct;36(5):e288-93. doi: 10.1016/j.canep.2012.05.001. Epub 2012 Jun 5.
A personal history of basal cell carcinoma (BCC) is associated with increased risk of other malignancies, but the reason is unknown. The hedgehog pathway is critical to the etiology of BCC, and is also believed to contribute to susceptibility to other cancers. This study tested the hypothesis that hedgehog pathway and pathway-related gene variants contribute to the increased risk of subsequent cancers among those with a history of BCC.
The study was nested within the ongoing CLUE II cohort study, established in 1989 in Washington County, Maryland, USA. The study consisted of a cancer-free control group (n=2296) compared to three different groups of cancer cases ascertained through 2007, those diagnosed with: (1) Other (non-BCC) cancer only (n=2349); (2) BCC only (n=534); and (3) BCC plus other cancer (n=446). The frequencies of variant alleles were compared among these four groups for 20 single nucleotide polymorphisms (SNPs) in 6 hedgehog pathway genes (SHH, IHH, PTCH2, SMO, GLI1, SUFU), and also 22 SNPs in VDR and 8 SNPs in FAS, which have cross-talk with the hedgehog pathway.
Comparing those with both BCC and other cancer versus those with no cancer, no significant associations were observed for any of the hedgehog pathway SNPs, or for the FAS SNPs. One VDR SNP was nominally significantly associated with the BCC cancer-prone phenotype, rs11574085 [per minor allele odds ratio (OR) 1.38, 95% confidence interval (CI) 1.05-1.82; p-value=0.02].
The hedgehog pathway gene SNPs studied, along with the VDR and FAS SNPs studied, are not strongly associated with the BCC cancer-prone phenotype.
基底细胞癌（BCC）的个人病史与其他恶性肿瘤的风险增加有关，但原因尚不清楚。刺猬通路对于 BCC 的病因至关重要，并且据信也有助于其他癌症的易感性。本研究检验了这样一个假设，即刺猬通路和通路相关基因变异与 BCC 病史患者随后癌症风险增加有关。
该研究嵌套在正在进行的 CLUE II 队列研究中，该研究于 1989 年在美国马里兰州华盛顿县成立。该研究包括一个无癌症对照组（n=2296），与通过 2007 年确定的三组不同癌症病例进行比较，这些病例诊断为：（1）仅其他（非 BCC）癌症（n=2349）；（2）仅 BCC（n=534）；和（3）BCC 加其他癌症（n=446）。在这四个组中比较了 6 个刺猬通路基因（SHH、IHH、PTCH2、SMO、GLI1、SUFU）中的 20 个单核苷酸多态性（SNP）和 22 个 VDR 中的 SNP 以及 8 个 FAS 中的 SNP 的变异等位基因频率，这些 SNP 与刺猬通路有交叉对话。
比较同时患有 BCC 和其他癌症与没有癌症的人，没有观察到任何刺猬通路 SNP 或 FAS SNP 存在显著关联。一个 VDR SNP 与 BCC 癌症易感性表型存在名义上的显著关联，rs11574085[每个次要等位基因的优势比（OR）1.38，95%置信区间（CI）1.05-1.82；p 值=0.02]。
研究的刺猬通路基因 SNP 以及研究的 VDR 和 FAS SNP 与 BCC 癌症易感性表型没有很强的关联。
