The risk of gastric cancer in carriers of CHEK2 mutations

Abstract

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∗1100delC Mutation and Risk of Prostate Cancer

“…Therefore, any mutation causing a malfunction of the CHEK2 protein decreases cellular ability to protect the integrity of DNA. Among numerous mutations identified in CHEK2, the best studied mutations in prostate cancer are 1100delC, IVS2+1G>A, I157T, and del5395 [12–17]. Three mutations (1100delC, IVS2+1G>A, and del5395) cause CHEK2 protein-truncation.…”

First evidence of a large CHEK2 duplication involved in cancer predisposition in an Italian family with hereditary breast cancer

“…More recently, common mutations in CHEK2 , such as 1100delC, I157T and IVS2 + 1G > A, have been associated with different types of cancer [15-17], but the association of CHEK2 mutations with Li-Fraumeni syndrome has been questioned because of different phenotypes in Li-Fraumeni patients and CHEK2 mutation carriers [18]. …”

The Prevalence of Founder Mutations among Individuals from Families with Familial Pancreatic Cancer Syndrome

“…The large germline deletion in CHEK2 is associated with an increased risk of prostate cancer [9]. The missense variant, I157T, is associated with an increased risk of colon, kidney, prostate, thyroid, and stomach cancers [8,11]. In light of existing research, it can be assumed that CHEK2 gene mutations are more specific to a certain percentage of cancers of the gastrointestinal tract.…”