In this study, we searched for CHEK2 mutations in young, high-risk breast cancer patients in China and detected a missense variant Y390C (1169A > G) in 12 of 150 patients (8.0%) and 2 in 250 healthy controls (0.8%, P = 0.0002).
The frequencies of the CHEK2 p.H371Y in familial and unselected breast cancer cases and controls were 4.24% (5/118), 1.76% (16/909), and 0.73% (9/1228), respectively.
The results are consistent with the hypothesis that CHEK2*1100delC multiplies the risks associated with susceptibility alleles in other genes to increase the risk of breast cancer.
Overall, our data suggest that mutations in CHEK2 may contribute to prostate cancer risk and that the DNA-damage-signaling pathway may play an important role in the development of prostate cancer.
Overall, our data suggest that mutations in CHEK2 may contribute to prostate cancer risk and that the DNA-damage-signaling pathway may play an important role in the development of prostate cancer.
This suggests that the biological mechanisms underlying the elevated risk of breast cancer in CHEK2 mutation carriers are already subverted in carriers of BRCA1 or BRCA2 mutations, which is consistent with participation of the encoded proteins in the same pathway.
The results suggest that CHEK2 acts as a low-penetrance tumor-suppressor gene in breast cancer and that it makes a significant contribution to familial clustering of breast cancer-including families with only two affected relatives, which are more common than families that include larger numbers of affected women.
Although CHEK2 is no longer recognized as a major determinant of the Li-Fraumeni syndrome, a hereditary condition predisposing to cancer at multiple sites, it cannot be ruled out that mutations of this gene play a role in malignancies arising in peculiar multi-cancer families.
The results are consistent with the hypothesis that CHEK2*1100delC multiplies the risks associated with susceptibility alleles in other genes to increase the risk of breast cancer.
The CHEK2 1100delC 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).