Hello Danica Rena

The genetic factors known to be involved in breast cancer risk comprise about 30 genes. These include the high-penetrance early-onset breast cancer genes, BRCA1 and BRCA2, a number of rare cancer syndrome genes, and rare genes with more moderate penetrance.

BRCA1 and BRCA2 genes, are the ones which contain over 1000 mutations. Genetic screening for the spectrum of important mutations in these genes in high-risk families is well established. The BRCA1 ‘breast cancer 1 early-onset’ gene is involved in susceptibility to breast and ovarian cancer at a young age, and tumors can arise through somatic or germline mutations. Impaired or lost BRCA1 function underlies substantial genome instability including increase in the number of mutations, DNA breakage and chromatid exchanges, increased sensitivity to DNA damage, and defects in cell-cycle checkpoint functions. The role of BRCA1 in the DNA damage response is that of ‘caretaker’ or ‘master regulator’ in the genome.

BRCA2 gene is a crucial element in the DNA repair process which, if impaired through mutation, can lead to chromosome instability and cancer. It is known to mediate recombinational DNA repair by promoting assembly of RAD51 onto single-stranded DNA. Mutations in the BRCA2 gene may disrupt this mechanism and impair repair of DNA breaks.

Germline mutations in the TP53 gene cause Li–Fraumeni syndrome, a phenotype which includes early-onset breast cancer, but these mutations are far rarer.

There are a number of syndromes that include breast cancer as a component of the disease phenotype. Rare to uncommon mutations in the PTEN and STK11 genes cause Cowden and Peutz–Jeghers syndromes, respectively, and both are associated with considerably increased breast cancer risk. The E-cadherin gene (CDH1) encodes a cellular adhesion protein and is a powerful tumor suppressor of breast cancer. It is particularly implicated in invasive lobular breast carcinomas. RAD51C is another gene involved in the recombinational repair of double-stranded DNA breaks. Rare germline mutations have been shown to confer increased risks of breast and ovarian cancer.

Epigenetics refers to changes in gene expression without changes in the DNA sequence. These include alterations in DNA methylation, histone post-translational modifications, recruitment of chromatin remodeling factors, and expression of micro (miR) and long (lncR) non-coding RNA.

Most of the breast cancer cases are sporadic, and are not related to germline mutations in genes such as the tumor suppressor gene, and usually occur later in life. Epigenetic modifications caused by environmental pollutants, foods, and drinking water are sources of xenobiotics including agonists of the AHR (PAH, dioxin, phthalates, PCB), BPA, and arsenic may contribute epigenetically by dysregulating tumor suppressor gene leading to breast cancer. These epigenetic modifications such as CpG methylation may be conserved through cycles of cell division and transmitted to cell progenies. The accumulation of epigenetic changes in tumor suppressor gene may contribute to the “cancer epigenome” in the same individual or subsequent generations even after removal of the stimuli.

A typical example is BRCA-1 whose repression through CpG methylation in sporadic breast tumors confers a “BRCAness” tumor phenotype similar to that generally seen in BRCA-1 mutation carriers. In mutation carriers (like BRCA-1), epigenetic silencing of the wild-type allele may contribute to loss of heterozygosity and breast tumor development.

Steps to lower the risk of getting breast cancer.

Genetic counseling and testing can be done to look for inherited mutations in the BRCA1 and BRCA2 genes (or less commonly in genes such as PTEN, TP53, or others mentioned above). This might be an option for some women who have been diagnosed with breast cancer, as well as for certain women with factors that put them at higher risk for breast cancer, such as a strong family history.

If one has a higher than usual risk of developing breast cancer, one could use the approach called "chemoprevention”. These are drugs that may help prevent breast cancer. For breast cancer, use of hormone-blocking drugs help to reduce cancer risk. When there is a BRCA1 or BRCA2 genetic mutation present, which substantially increases the risk of breast cancer, preventive removal of breasts may be considered.

Best.

Perfectly Said Dr Malcolm Nobre

BRAC1 and BRAC2 are genes mutation associated with breast cancer. So by the above information breast cancer occurrence is correlated to genetics.