晚期糖基化终产物受体(RAGE)的过表达与慢性炎症有关,这反过来又与结直肠癌风险增加有关。可溶性RAGE(sRAGE)与RAGE竞争结合其配体,从而潜在地预防RAGE诱导的炎症。
研究sRAGE和相关遗传变异是否与结直肠癌风险相关,我们在欧洲癌症与营养前瞻性调查(EPIC)中进行了一项巢式病例对照研究.通过ELISA在1,361例结直肠癌匹配的病例对照组中测量血浆sRAGE浓度。与sRAGE浓度相关的基因中编码的24个SNP可用于1,985例大肠癌病例和2,220例对照。使用条件和非条件逻辑回归计算结直肠癌风险和循环sRAGE和SNPs的多变量调整OR和95%置信区间(CIs)。分别。
较高的sRAGE浓度与结直肠癌呈负相关(ORQ5vs.第一季度,0.77;95%CI,0.59-1.00)。性别特异性分析显示,观察到的反向风险关联仅限于男性(ORQ5vs。第一季度,0.63;95%CI,0.42-0.94),而在女性中未观察到关联(ORQ5vs.Q1,1.00;95%CI,0.68-1.48;性别的P异质性=0.006)。携带rs653765(ADAM10的启动子区域)的次要等位基因的参与者具有较低的结直肠癌风险(Cvs.T,OR,0.90;95%CI,0.82-0.99)。
诊断前sRAGE浓度与男性结直肠癌风险呈负相关,但不是女人。位于ADAM10基因内的SNP,关于愤怒的脱落,与结直肠癌风险相关。
需要进一步的研究来证实我们观察到的性别差异,并更好地探索sRAGE遗传变异在结直肠癌发展中的潜在参与。
Overexpression of the receptor for advanced glycation end-product (RAGE) has been associated with chronic inflammation, which in turn has been associated with increased colorectal cancer risk. Soluble RAGE (sRAGE) competes with RAGE to bind its ligands, thus potentially preventing RAGE-induced inflammation.
To investigate whether sRAGE and related genetic variants are associated with colorectal cancer risk, we conducted a nested case-control
study in the European Prospective Investigation into Cancer and Nutrition (EPIC). Plasma sRAGE concentrations were measured by ELISA in 1,361 colorectal cancer matched case-control sets. Twenty-four SNPs encoded in the genes associated with sRAGE concentrations were available for 1,985 colorectal cancer cases and 2,220 controls. Multivariable adjusted ORs and 95% confidence intervals (CIs) were computed using conditional and unconditional logistic regression for colorectal cancer risk and circulating sRAGE and SNPs, respectively.
Higher sRAGE concentrations were inversely associated with colorectal cancer (ORQ5vs.Q1, 0.77; 95% CI, 0.59-1.00). Sex-specific analyses revealed that the observed inverse risk association was restricted to men (ORQ5vs.Q1, 0.63; 95% CI, 0.42-0.94), whereas no association was observed in women (ORQ5vs.Q1, 1.00; 95% CI, 0.68-1.48; P heterogeneity for sex = 0.006). Participants carrying minor allele of rs653765 (promoter region of ADAM10) had lower colorectal cancer risk (C vs. T, OR, 0.90; 95% CI, 0.82-0.99).
Prediagnostic sRAGE concentrations were inversely associated with colorectal cancer risk in men, but not in women. An SNP located within ADAM10 gene, pertaining to RAGE shedding, was associated with colorectal cancer risk.
Further studies are needed to confirm our observed sex difference in the association and better explore the potential involvement of genetic variants of sRAGE in colorectal cancer development.