Women with a truncating mutation in CHEK2 and a positive family history of breast cancer have a lifetime risk of breast cancer of greater than 25% and are candidates for magnetic resonance imaging screening and for tamoxifen chemoprevention.
We screened the entire coding region of CHEK2 gene on 59 high-risk breast cancer patients who tested negative for BRCA1/2 germline mutations from UKM Medical Centre (UKMMC), Hospital Kuala Lumpur (HKL) and Hospital Putrajaya (HPJ).
We screened the coding exons and proximal splice junction regions of the gene for germline sequence variation in 1,330 early-onset breast cancer cases and 1,123 controls from the Breast Cancer Family Registry, using the same population-based sampling and analytical strategy that we developed for assessment of rare sequence variants in ATM and CHEK2.
We screened a cohort of 2334 Chinese women with operable primary breast cancer who received a neoadjuvant chemotherapy regimen for CHEK2H371Y germline mutations.
We genotyped these six tagSNPs in 1,577 postmenopausal breast cancer cases and 1,513 population controls, but found no convincing association between any common CHEK2 haplotype and breast cancer risk.
We estimate that the CHEK21100delC allele is associated with an odds ratio of 2.6 for breast cancer, which corresponds to a lifetime risk of approximately 24% in Ontario.
We conclude that the 1100delC mutation of the CHEK2 gene contributes little to the overall breast cancer burden in Poland, including familial cases of this malignancy.
We conclude that somatic CHK2 mutations are rare in breast cancer, but our results suggest a tumor suppressor function for CHK2 in a small proportion of breast tumors.
We also found evidence of association with breast cancer risk for three variants in CHEK2, c.349A>G OR 2.26 (95% CI 1.29 to 3.95), c.1036C>T OR 5.06 (95% CI 1.09 to 23.5) and c.538C>T OR 1.33 (95% CI 1.05 to 1.67) (p≤0.017).
We aimed to assess whether CHEK2 was subject to DAE in lymphoblastoid cell lines (LCLs) from high-risk breast cancer patients for whom no mutation in BRCA1 or BRCA2 had been identified.
Together, these data suggest a functional link between recombination control and breast cancer predisposition in carriers of Chk2 and BRCA1 germ line mutations.
To investigate if other CHEK2 variants confer an increased risk of breast cancer, we have screened an affected individual with breast cancer from 68 breast cancer families.
To extend our knowledge on the role of CHEK2 in susceptibility to male breast cancer we have screened a series of 26 breast cancer cases with male representation for germline sequence variation in the CHEK2 gene.
To distinguish the roles of Chk1 and Chk2 in S and G(2) checkpoints after DNA damage, derivatives of the human breast cancer cell line MDA-MB-231 were established that express short hairpin RNAs to selectively suppress Chk1 or Chk2 expression.