Sébastien Küry, Céline Garrec, Fabrice Airaud, Flora Breheret, Virginie Guibert, Cécile Frenard, Stéphane Bezieau, CHU Nantes, Service de Génétique Médicale, 44093 Nantes CEDEX 1, France.
World J Gastroenterol. 2014 Jan 7;20(1):204-13. doi: 10.3748/wjg.v20.i1.204.
To evaluate the risk associated with variants of the UNC5C gene recently suspected to predispose to familial colorectal cancer (CRC).
We screened patients with familial CRC forms as well as patients with sporadic CRCs. In a first time, we analyzed exon 11 of the UNC5C gene in 120 unrelated patients with suspected hereditary CRC, 58 patients with suspected Lynch-associated cancer or polyposis, and 132 index cases of Lynch syndrome families with a characterized mutation in a DNA mismatch repair (MMR). Next, 1023 patients with sporadic CRC and 1121 healthy individuals were screened for the variants identified in patients with familial cancer.
Of 120 patients with familial CRC of unknown etiology, one carried the previously reported mis-sense mutation p.Arg603Cys (R603C) and another exhibited the unreported variant of unknown significance p.Thr617Ile (T617I). The p.Ala628Lys (A628K) mutation previously described as the main UNC5C risk variant for familial CRC was not detected in any cases of familial CRC of unknown etiology, but was present in a patient with familial gastric cancer and in two Lynch syndrome patients in co-occurrence with MMR mutations. A statistically non-significant increase in cancer risk was identified in familial CRC and/or other Lynch-associated cancers (1/178 patients vs 2/1121 healthy controls, OR = 3.2, 95%CI: 0.29-35.05, P = 0.348) and in sporadic CRCs (4/1023 patients vs 2/1121 healthy controls, OR = 2.2, 95%CI: 0.40-12.02, P = 0.364).
We confirm that UNC5C mutations are very rare in familial and sporadic CRCs, but further investigations are needed to justify routine UNC5C testing for diagnostic purposes.
评估 UNC5C 基因变异与家族性结直肠癌（CRC）易感性相关的风险。
我们筛选了家族性 CRC 患者以及散发性 CRC 患者。首先，我们分析了 120 例疑似遗传性 CRC 患者、58 例疑似林奇相关癌症或息肉患者和 132 例林奇综合征家族的 UNC5C 基因外显子 11，这些家族的 DNA 错配修复（MMR）基因突变均已明确。接下来，我们筛选了 1023 例散发性 CRC 患者和 1121 例健康对照者，以检测家族性癌症患者中发现的变异。
在 120 例病因不明的家族性 CRC 患者中，1 例携带先前报道的错义突变 p.Arg603Cys（R603C），另 1 例携带尚未报道的意义不明的变异 p.Thr617Ile（T617I）。先前描述的 UNC5C 家族性 CRC 的主要风险变异 p.Ala628Lys（A628K）在病因不明的家族性 CRC 患者中均未检出，但在 1 例家族性胃癌患者和 2 例林奇综合征患者中与 MMR 突变共存。在家族性 CRC 和/或其他林奇相关癌症（178 例患者中有 1 例 vs 1121 例健康对照者中有 2 例，OR=3.2，95%CI：0.29-35.05，P=0.348）和散发性 CRC 患者（1023 例患者中有 4 例 vs 1121 例健康对照者中有 2 例，OR=2.2，95%CI：0.40-12.02，P=0.364）中，癌症风险略有增加，但无统计学意义。
我们证实 UNC5C 突变在家族性和散发性 CRC 中非常罕见，但需要进一步研究以证明常规 UNC5C 检测用于诊断目的的合理性。
