Department of Genetics and Pathology, International Hereditary Cancer Centre, Pomeranian Medical University, Szczecin, Poland.
Fam Cancer. 2013 Sep;12(3):473-8. doi: 10.1007/s10689-012-9599-2.
CHEK2 is a tumor suppressor gene whose functions are central to the induction of cell cycle arrest and apoptosis following DNA damage. Mutations in CHEK2 have been associated with cancers at many sites, including breast and prostate cancers, but the relationship between CHEK2 and gastric cancer has not been extensively studied. In Poland, there are four known founder alleles of CHEK2; three alleles are protein truncating (1100delC, IVS2G>A, del5395) and the other is a missense variant (I157T). We examined the frequencies of four Polish founder mutations in the CHEK2 gene in 658 unselected gastric cancer patients, in 154 familial gastric cancer patients and in 8,302 controls. A CHEK2 mutation was seen in 57 of 658 (8.7 %) unselected patients with gastric cancer compared to 480 of 8,302 (5.8 %) controls (OR 1.6, p = 0.004). A CHEK2 mutation was present in 19 of 154 (12.3 %) familial cases (OR = 2.3, p = 0.001). The odds ratio for early onset (<50 years) gastric cancer was higher (2.1, p = 0.01), than for cases diagnosed at age of 50 or above (OR 1.4, p = 0.05). Truncating mutations of CHEK2 were associated with higher risk (OR = 2.1, p = 0.02) than the missense mutation I157T (OR = 1.4, p = 0.04). CHEK2 mutations predispose to gastric cancer, in particular to young-onset cases.
CHEK2 是一种肿瘤抑制基因，其功能对于 DNA 损伤后细胞周期停滞和细胞凋亡的诱导至关重要。CHEK2 中的突变与许多部位的癌症有关，包括乳腺癌和前列腺癌，但 CHEK2 与胃癌之间的关系尚未得到广泛研究。在波兰，CHEK2 有四个已知的突变基因；其中三个是蛋白截断突变（1100delC、IVS2G>A、del5395），另一个是错义突变（I157T）。我们在 658 例未经选择的胃癌患者、154 例家族性胃癌患者和 8302 例对照中检测了 CHEK2 基因中的四个波兰突变基因的频率。在 658 例未经选择的胃癌患者中，有 57 例（8.7%）存在 CHEK2 突变，而在 8302 例对照中，有 480 例（5.8%）存在 CHEK2 突变（OR 1.6，p=0.004）。在 154 例家族性病例中，有 19 例（12.3%）存在 CHEK2 突变（OR=2.3，p=0.001）。早发性（<50 岁）胃癌的比值比更高（2.1，p=0.01），而年龄在 50 岁或以上的病例比值比为 1.4（p=0.05）。与错义突变 I157T 相比，CHEK2 的截断突变与更高的风险相关（OR=2.1，p=0.02）。CHEK2 突变易患胃癌，尤其是早发性胃癌。
