A hospital-based case-control study, including 1,121 cases and 1,056 controls was conducted to evaluate the association between eight selected single nucleotide polymorphisms (SNPs) (rs35514263 in <i>ATR</i>; rs492510, rs558351 in <i>CHKE1</i>; rs189037 in <i>ATM</i>; rs2236141, rs5762748, rs2236142 and rs9620817 in <i>CHEK2</i>) in ATR-CHEK1 and ATM-CHEK2 pathways and the risk of colorectal cancer in a Chinese population by using TaqMan method.
Cumulative epidemiological evidence for a significant association with CRC risk was graded strong for eight variants in five genes (adenomatous polyposis coli (APC), CHEK2, DNMT3B, MLH1 and MUTYH), moderate for two variants in two genes (GSTM1 and TERT), and weak for 52 variants in 45 genes.
This phenotype is induced by overexpression of the oncogene AURKA or by loss of the tumour suppressor gene CHK2, a genetic constitution found in 73% of human colorectal cancers.
This meta-analysis demonstrates that the CHEK2I157T variant was an important cancer gene, which increases cancer risk, especially in breast and colorectal cancer in Caucasian, and the bioinformatic analysis showed this change was mainly attributed to the decreased hydrophobicity of CHEK2 157T.
Our result demonstrate for the first time that CHEK21100delC, IVS2+1G>A and I157T mutations have not been agenetic susceptibility factor for CRC in the Turkish population.
We conclude that CHEK2I157T is not relevant for CRC risk in Bulgaria, but studies on a larger scale might help evaluate its possible significance in respect to disease characteristics.
The increased risk of CRC was associated with mutations in CHEK2 gene region involving fork head-associated domain [39/631 (6.2%) cases versus 19/683 (2.8%) controls; odds ratio (OR)=2.3; 95% confidence interval (CI)=1.3-4.0; p=0.003], and with the most frequent I157T mutation [30/631 (4.8%) cases versus 17/683 (2.5%) controls; OR=2.0; 95% CI=1.1-3.6; p=0.03].
In summary, our data suggest that the CHEK21100delC is not a major cause of double primary breast and colorectal cancer in Sweden, which suggests that this patient group should not routinely be screened for the CHEK21100delC variant.
LOH across the CHEK2 locus is common in sporadic breast, ovarian, and colorectal cancers, but point mutation or epigenetic inactivation of the retained allele is uncommon.
It is also concluded that CHEK2 protein abrogation is not caused by the CHEK2 germline variants R117G, R137Q, R145W, I157T, and R180H in familial colorectal cancer.
In this study, using 6-thioguanine (6-TG) as a mismatch-inducing drug, we examine the role of ataxia telangiectasia mutated (ATM)/CHK2 and ATM and Rad-3 related (ATR)/CHK1 signaling pathways in MMR-mediated cell cycle responses in MMR-proficient human colorectal cancer RKO cells.
The CHEK21100delC mutation was, however, not the major predisposing factor for the HBCC phenotype but appeared to act in synergy with another, as-yet-unknown susceptibility gene(s).