Young-onset colorectal cancer is associated with a personal history of type 2 diabetes
Young-onset colorectal cancer is associated with a personal history of type 2 diabetes
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DOI：
10.1111/ajco.13428
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发表时间：
2020-09-03
影响因子：
1.9
通讯作者：
Young, Joanne P.
中科院分区：
文献类型：
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作者：
Mikaeel, Reger R.;Symonds, Erin L.;Young, Joanne P.
背景 结直肠癌 (CRC) 在年轻人中的发病率正在上升，而这一现象目前尚无法解释。我们调查了有 2 型糖尿病 (T2D) 个人病史是否是年轻发病结直肠癌 (YOCRC) 的潜在危险因素。方法 南澳大利亚年轻发病 (SAYO) CRC 研究是一系列 55 岁以下患有 CRC 的年轻人。该研究招募了 90 名不相关的 YOCRC 病例。 T2D 的个人病史和详细家族史是通过面对面访谈获得的，并从病历中得到确认。对每个 CRC 病例的种系 DNA 进行全外显子组测序。 T2D 个人病史研究的对照是 240 名经结肠镜检查证实无已知 CRC 易感性的患者。结果 YOCRC病例的中位年龄为44岁（18-54），对照者的中位年龄为45岁（18-54），且病例和对照者中女性均为53%（P = 0.99）。 67/89 (75%) 的病例可见左侧（远端）CRC。与对照组相比，17/90 (19%) YOCRC 患者有 T2D 个人病史（12/240，5%；P < 0.001；比值比 = 4.4；95% 置信区间，2.0-9.7）。 YOCRC 患者经常报告至少一名一级亲属患有 T2D（32/85，38%）。 87 例 YOCRC 病例中，有 10 例（12%）具有 CRC 相关致病性种系变异，但未发现家族性糖尿病相关基因的致病性变异。结论 尽管机制尚不清楚，但我们的观察表明 YOCRC 患者的 T2D 个人史有所丰富。影响 因此，T2D 的诊断可能会识别出 CRC 风险较高的年轻成人子集，并且对这些人进行早期筛查可能是合适的。
Background Colorectal cancer (CRC) is rising in incidence in young adults, and this observation is currently unexplained. We investigated whether having a personal history of type 2 diabetes mellitus (T2D) was a potential risk factor for young-onset colorectal cancer (YOCRC). Methods The South Australian Young Onset (SAYO) CRC study is a series of young adults with CRC below age 55. Ninety unrelated YOCRC cases were recruited to the study. Personal history and detailed family history of T2D were obtained at face-to-face interview and confirmed from medical records. Whole exome sequencing was conducted on germline DNA from each CRC case. Controls for personal history studies of T2D were 240 patients with proven clear colonoscopies and no known CRC predispositions. Results The median age of YOCRC cases was 44 years (18-54) and of controls was 45 years (18-54), and 53% of both cases and controls were females (P = 0.99). Left-sided (distal) CRC was seen in 67/89 (75%) of cases. A personal history of T2D was confirmed in 17/90 (19%) YOCRC patients compared with controls (12/240, 5%;P < 0.001; odds ratio = 4.4; 95% confidence interval, 2.0-9.7). YOCRC patients frequently reported at least one first-degree relative with T2D (32/85, 38%). Ten of 87 (12%) of YOCRC cases had CRC-related pathogenic germline variants, however, no pathogenic variants in familial diabetes-associated genes were seen. Conclusions Though the mechanism remains unclear, our observations suggest that there is enrichment for personal history of T2D in YOCRC patients. Impact A diagnosis of T2D could therefore potentially identify a subset of young adults at increased risk for CRC and in whom early screening might be appropriate.