We conducted a national population-based study of Israeli women to determine the influence, if any, of a BRCA1 or a BRCA2 mutation on the prognosis in breast cancer.
Recent evidence for the interactions of ataxia-telangiectasia mutated protein ATM and breast cancer susceptibility proteins BRCA1 and BRCA2 (identified as FANCD1) with other known FA proteins suggests that FA proteins have a significant role in DNA repair/recombination and cell cycle control.
The discovery of the BRCA1 and BRCA2 genes has explained some of the genetic determinants of breast cancer risk, but these genes alone do not explain all of the familial aggregation of breast cancer.
In summary, BRCA1 and BRCA2 mutations are not uncommon in Cuban women with breast cancer, but the absence of founder mutations precludes the development of a rapid and inexpensive clinical screening test.
Increased risk of pancreatic cancer has been reported in breast cancer families carrying BRCA1and BRCA2 mutations; however, pancreatic cancer risk in mutation-negative (BRCAX) families has not been explored to date.
To estimate the relative contribution of two important regional recurrent mutations (BRCA1 founder mutation IVS12-1643del3835 and BRCA2 founder mutation 5579insA) to the overall occurrence of breast cancer, we performed a population-based study in two specific small regions.
Our study shows that -26 5' UTR polymorphism in BRCA2 can modulate the fine-tuned regulation of the multifunctional gene BRCA2 and renders risk or protection according to the genotype status in the sporadic form of breast cancer, which is further influenced by the germline genetic backgrounds of codon 72 polymorphism of p53.
Fanconi anemia (FA) proteins function in a DNA damage response pathway that appears to be part of the network including breast cancer susceptibility gene products, BRCA1 and BRCA2.
Breast cancer 1 antigen (BRCA 1) and breast cancer 2 antigen (BRCA2) genes play a significant role in deoxyribonucleic acid (DNA) repair by means of interstrand crosslink repair, and deleterious germline mutations of these are responsible for most hereditary breast and ovarian cancers.
Pathogenic mutations in the tumour suppressor genes BRCA1 and BRCA2 confer increased risks for breast and ovarian cancer and account for approximately 15% of the excess familial risk of breast cancer amongst first-degree relatives of patients with breast cancer.
When the analyses were restricted to families that had been negative for mutations in the breast/ovarian cancer susceptibility genes, BRCA1 and BRCA2, the ovarian cancer risk was 11.59 (3.12-29.7) and that of breast cancer 3.32 (1.52-6.31).
Two highly penetrant genes that predispose individuals to breast cancer (BRCA1 and BRCA2) are known to confer an increased risk of prostate cancer of about 3-fold and 7-fold, respectively, in breast cancer families.
In the BRCA1 families the RR tended to be higher [RR 1.30, 95% confidence interval (CI) 0.63--2.70] and in the BRCA2 families lower (RR 0.78, 95% CI 0.39--1.57) than among the general breast cancer patient population.
To investigate whether or not RAP80 is also a breast cancer susceptibility gene, we sequenced the entire exonic regions of RAP80 in the germline DNA of 152 women with familial breast cancer, who were previously found to be negative for BRCA1 and BRCA2 mutations.No truncating mutation was identified.
In this prospective study, we estimate breast cancer risks in women with a family history of breast cancer and for whom the proband tested negative for a mutation in BRCA1 or BRCA2.
The estimated cumulative risks of breast cancer by age 70 years were 37.9 % [95 % confidence interval (CI) 24.1-54.4 %] for BRCA1 mutation carriers and 36.5 % (95 % CI 26.7-51.8 %) for BRCA2 mutation carriers, respectively.
A single-nucleotide polymorphism (SNP) in the 5'-untranslated region (UTR) of RAD51, 135G>C (rs1801320), was reported to be associated with an increased risk of breast cancer among BRCA2 as well as BRCA1 carriers.
Mutations in the DNA damage response (DDR) factors, breast cancer 1 (BRCA1) and BRCA2, sensitize tumor cells to poly(ADP-ribose) polymerase (PARP) inhibitors.
Of all inherited predispositions to breast cancer in the NYBCS, 73.8% (104 of 142) were due to a BRCA1 or BRCA2 founder allele, 4.9% (7 of 142) to another BRCA1 or BRCA2 mutation, and 21.8% (31 of 142) to a mutation in another gene.