K.G. Jebsen Center for Genome-Directed Cancer Therapy, Department of Clinical Science, University of Bergen, Bergen, Norway.
Department of Oncology, Haukeland University Hospital, Bergen, Norway.
Biomarkers. 2021 Jun;26(4):302-308. doi: 10.1080/1354750X.2021.1891291. Epub 2021 Feb 28.
While large GWAS analyses have not found convincing associations between promoter SNP55 and gynaecological cancers, SNP55 is in linkage disequilibrium with two other functional SNPs in the same promoter, likely to obscure associations between single SNPs and cancer risk. Here, we assessed the impact of SNP55 on risk of endometrial and ovarian cancer, including sub-analyses stratified for other functional SNPs in the region.
Using a custom LightSNiP assay, we genotyped SNP55 in two large hospital-based cohorts of patients with ovarian (n = 1,332) and endometrial (n = 1,363) cancer and compared genotypes to healthy female controls (n = 1,858).
Among individuals harbouring the SNP309TT genotype, the minor SNP55T-allele was associated with a reduced risk of endometrial (dominant model: OR = 0.63; CI = 0.45-0.88; = 0.01). Regardless of the genotype in neighbouring SNPs, the SNP55T-allele was also associated with a reduced risk of endometrial cancer before 50 years of age (dominant model: OR = 0.56; CI = 0.34-0.90; = 0.02). No association between SNP55 status and ovarian cancer risk was observed.
SNP55T-allele may correlate with reduced risk for endometrial cancer in a SNP309T-, but not SNP309G, context.
尽管大型全基因组关联研究（GWAS）并未发现 SNP55 启动子与妇科癌症之间存在令人信服的关联，但 SNP55 与同一启动子中的另外两个功能 SNP 处于连锁不平衡状态，这可能会掩盖单个 SNP 与癌症风险之间的关联。在这里，我们评估了 SNP55 对子宫内膜癌和卵巢癌风险的影响，包括对该区域中其他功能 SNP 进行分层的亚分析。
使用定制的 LightSNiP 检测方法，我们对两个大型基于医院的卵巢癌（n=1332）和子宫内膜癌（n=1363）患者队列以及 1858 名健康女性对照者进行了 SNP55 基因分型。
在携带 SNP309TT 基因型的个体中，SNP55T 等位基因与子宫内膜癌风险降低相关（显性模型：OR=0.63；95%CI=0.45-0.88； =0.01）。无论相邻 SNP 的基因型如何，SNP55T 等位基因也与 50 岁以下子宫内膜癌风险降低相关（显性模型：OR=0.56；95%CI=0.34-0.90； =0.02）。未观察到 SNP55 状态与卵巢癌风险之间存在关联。
SNP55T 等位基因可能与 SNP309T 而非 SNP309G 背景下的子宫内膜癌风险降低相关。
