Abstract
Known genetic mutations and familial hereditary factors account for less than 20–25% of breast cancer cases in women, therefore, most instances have been classified as sporadic cases of unknown aetiologies. Single nucleotide polymorphisms (SNPs) were considered as breast cancer risk factors, but numerous studies have failed to support this assertion. Recent evidence correlates aberrant epigenetic mechanisms in the development and metastatic progression of breast cancer, yet there has been limited progress made to identify the primary aetiology underlying sporadic cases of breast cancer. This has led some researchers to consider alternative hypotheses including in utero exposure to deleterious chemical agents during early development, the immortal strand and the strand-specific imprinting and selective chromatid segregation hypotheses. Here, we integrate prominent alternate models to help guide future research on this very important topic concerning human health.
Highlights
Known genetic mutations and familial hereditary factors account for less than 20–25% of breast cancer cases in women, most instances have been classified as sporadic cases of unknown aetiologies
A large multistage study for susceptibility alleles identified four novel suspect genes, yet the results revealed that a high proportion of the general population carries susceptibility Single nucleotide polymorphisms (SNPs) without developing the disease and that the increased risk associated with these alleles is relatively small [10]
We suggest that r/r genotype increases the rate of mitotic recombination, as compared to that of the R/R and R/r genotype, leading to Loss of Heterozygosity (LOH) across the genome, including chromosome regions where genes mutations or tumor suppressor genes (TSG) implicated in breast cancer development lie
Summary
Another idea considers possible fetal growth influences on breast cancer development and proposes that the number of mammary-specific stem cells, which is determined in utero or soon after birth, correlates with the likelihood of developing breast cancer [25,26]. In 1975, John Cairns put forth a hypothesis to elucidate possible function of previously reported observations of non-random sister chromatid segregation [46,47] His immortal strand hypothesisposits that stem cells divide by asymmetric cell division, with one daughter cell ordained to become stem cell while the other fated to differentiate, by an unknown mechanism. In principle, biased distribution of only a few select chromosomes would be sufficient to accomplish cell-type specific functions, such as cellular differentiation or laterality development, and will not necessarily be limited to maintaining stem cell populations This point remains important in the context of the information discussed, where selective segregation of epigenetically distinct sister chromatids is proposed as a molecular mechanism for generating the asymmetric cell division, an essential requirement for developmental precision
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