Breast Cancer
Introduction
Cancer of the breast is the most widely observed malignancy in women around the world, and a lot of research has been conduct on this non-communicable disease. Genetic and non-genetic factors are both involved in scientific study of the cause of breast cancer. The studies have involved different set factors that have been related to increased risk of breast cancer development and even reduction of these risks. These aspects include ATM (ataxia telangiectasia mutated) gene polymorphisms, genes related to Vitamin C and the interaction between environment and genes, and the interaction between known Environment Risks Factors and susceptibility of Common Breast Cancer Loci .
There remains gap in the explanations of breast cancer familial clustering other than BRCA1 (Breast Cancer Gene 1), carriers of BRCA2 and breast cancer risk in specific uncommon syndromes resulting from mutations of various genes like TP53. Ataxia telangiectasia disorder affects many body parts and increases the malignancy risks (Nickels et.al 2013). Carcinogens may stimulate different kinds of DNA damages, but ATM protein play a major role in recognizing and repair of DNA DSBs. ATM protein is activated quickly and may phosphorylate many downstream substrates, and some of these substrates play a key role in regulating the arrest of cell cycle, repairing DNA and even apoptosis, by activating and stabilizing the p53 (Nickels et.al 2013).
There can also be interaction between ATM protein with oncongenic protein, BRCA1 that suppresses any tumor, checkpoint Kinase and NBSI that repairs DNA. A research that sought to determine ATM gene polymorphisms genetic frequencies, and examining the link between ATM genotypes and increase breast cancer risk involved the voluntary participation of 1232 cancer patients in Taiwan, China. The study excluded patients with history of malignancy, metastasized cancer form unknown causes or those with genetic diseases. There were two groups of participants; 1232 cancer patients and 1232 female controls matched by age. No significant differences were noted between both groups at various ages including menopause, first birth of a baby and enrolment. The results showed that ATM gene increases the risk of cancer, even though it plays a major role in pathways for DNA damage-repair (Nickels et.al 2013). Even though some studies have previous associated the heterozygous carriers of female ATM with increased risk of cancer especially in Westerns countries , there is no association of such relation found in Taiwan that has a high prevalence of breast cancer , more deaths and early onset where ATM plays the function of genetic marker. However, the allele for ATM rs189037 A was suggested to be likely to increase breast cancer risk (Nickels et.al 2013).
BRCA1and BRCA2 have been known to present high risk of mutations and hence breast cancer even though there other variants that lead to moderate susceptibility of breast cancer including ATM , CHEK2 and PALB2. In combination, these variants have been shown to explain 20- 25 percent of risks of breast cancer that are familial (Travis et. al 2010). Knowledge about possible modification of common susceptibility loci risks through environmental risk factors – lifestyle risk and reproductive factors – could offer insights into how cancer develops and especially the breast cancer causation for certain types of cancer. After many comparisons in large studies done recently, there has not been found any evidence that is statistically considerable to show multiple interactions between gene-environment and known breast cancer risk factors and susceptibility loci (Travis et. al 2010). The absence of such evidence can be attributed to partly to limited capacity for detecting weal interaction between gen and environment and failing to take into account certain kinds of breast cancer. An evaluation of whether single-nucleotide polymorphism relative risks at various loci fluctuate in relation to some known risk factors can be done using different studies. In one such evaluation, the breast cancer assessment was done with negative and positive status of estrogen receptor (Travis et. al 2010).
After the evaluation was done with more environmental risk factors and recently established familiar susceptibility loci, there was showed apparent independent replication, and that there is interaction for both Estrogen Receptor – positive and Estrogen Receptor –negative condition. Lack of similarity in interaction can be said to be plausible because birth’s number and SNP do not show heterogeneity through Estrogen Receptor status in relation to risk of breast cancer. As such, the study found finds evidence of any relation between LSP1-rs3817198, which increases cancer risk, and women being porous (Travis et. al 2010). The heterogeneity effect of LSP1-rs3817198 seems to be resulting partly from considerable negative association between births number in porous women and immune genotype. In addition, there is an increased risk of developing cancer of the breast for those women who drink alcohol. Alcohol in this case is an environmental risk factor. Caspase 8 protein is key in initiation of death cells and its activation result from damage of DNA by factors such as alcohol, a big cause of oxidative stress that is ethanol related. Most SNPs variations have been shown to be only indicators of the impact of present causal variants in a gene (Travis et. al 2010). Hence, the interaction of the gene and the environment with existing causal variants may have a larger modifying impact on breast cancer relative risk.
Some susceptibility loci of breast cancer that are low-penetrance have been established in various genome related studies, but there is little knowledge about the effect of environmental factors such as behavioral, reproductive and anthropometric risks .A study of interaction between gene and environmental factors done with the participation of 7610 women suffering from breast cancer was done to explore more knowledge on the same. The analysis included 7610 female patients suffering from incident breast cancer and 10196 healthy women, with a mean age of 60 years (Travis et. al 2010). On average , all the cases were probably less porous , were older during first birth , the body-mass index was more , more consumption of alcohol , and were more likely to be under Hormone Replacement Therapy than other controls. Ten environmental factors were assessed to check whether could be linked to 12 SNPs (single-nucleotide polymorphism) variations. After multiple testing was done, there were no considerable relations between eleven of the twelve polymorphisms and the risk factors. The strongest indication of association was the between alcohol consumption and gene CASP8-rs104548 (Travis et. al 2010). There was increased and greater risk for women who reported a history of alcohol intake – one drink each day – than those who took less alcohol. After many tests were done, the association was not significant. There were no material differences after women were subdivided into more than two groups and the risk factors were considered continuous (Travis at. al 2010).
Present use of Hormone Replacement Therapies was associated with more risk of developing cancer of the breast and more effect on oestrogen-receptor -positive tumors that the negative ones. But such was not seen after many tests. After multiple tests were done none of the environmental factors showed any significant relations with increased cases of cancer development (Travis et. al 2010). In addition, there was no strong link between the risk factors and the genotype under study were established which seems to show that susceptibility loci examined do not have effect on risk of breast cancer through by use of mechanisms that involve environmental factors (Travis et. al 2010). There are, however, some relative risks associated with some genotype and the relation to between cancer risk and environmental factors could not be proved most likely due to limited power to detect such interaction. While many environmental risk factors are associated with cancer development, few associating is done on genotype factors. For instance, taller women have a slightly higher risk of developing breast cancer than shorter female, and the shorter ones the major carriers of the high risk genes (Travis, et. al 2010).
On the cancer prevention , North- South gradients observations in cancer of breast mortality and prevalence has made researchers to develop a theory holding that vitamin D may be necessary in cancer prevention . The role of this Vitamin has been supported by huge experimental evidence, in relation to the fact that it regulates proliferation and differentiation of breast cells. However, there is need to examine the relations between risk of breast cancer and polymorphisms in SNPs genes related to vitamin D (Fuhrman, et. al 2013). A study in the same, using participants who in previous studies have indicated no history of breast cancer, has been done to examine this association. More than half of the participants, who passed the criteria, indicated an occurrence of primary cancer of breast in the period between previous surveys. The inclusion of sun exposures measures was necessary since vitamin D is synthesized by the skin after being exposed to sunlight. The various established risk factors for breast cancer were involved including menopause age, menarche age, full pregnancy numbers, and first birth age and breast cancer history (Fuhrman, et. al 2013).
There was observed a disproportionate trend in risk of breast cancer in relation with rare alleles number for Bsml variant and no material association with such risk was established for polymorphism related to FOK1. There was no significant difference between breast cancer controls and incidents in regard to a person’s residence geographical location (Fuhrman, et. al 2013). There is no material risk trend observed across different ambient sunlight average each year. The study established that there was an association between risk of breast cancer and vitamin D genes SNPS. Such risks are likely to mostly affect younger women in the adolescence since their breast tissues have not differentiated, and may pose a greater risk for cancer in later life (Fuhrman, et. al 2013). Therefore, the Vitamin D pathways were found to be associated with more risk even tough further support was need to prove the case.
Conclusion
Genetic and non-genetic factors are both involved in scientific study of the cause of breast cancer. The association between risk of developing breast cancer, the genotype factors and the environmental factors has been studied extensively over the years. The results of these studies have not been consistent as to clearly establish the cause breast cancer development, even though genetic and environmental risks factors have largely been established. There different aspects that have been attributed to the limitation of these studies and which need to be addressed to establish breast cancer causation.
References
Wang, H. C., Chang, W. S., Tsai, R. Y., Tsai, C. W., Liu, L. C., Su, C. H., ... & Bau, D. T. (2010). Association between ataxia telangiectasia mutated gene polymorphisms and breast cancer in Taiwanese females. Anticancer research, 30(12), 5217-5221.
Nickels, S., Truong, T., Hein, R., Stevens, K., Buck, K., Behrens, S., ... & Gaudet, M. (2013). Evidence of gene–environment interactions between common breast cancer susceptibility loci and established environmental risk factors. PLoS Genet, 9(3), e1003284.
Travis, R. C., Reeves, G. K., Green, J., Bull, D., Tipper, S. J., Baker, K., ... & Lathrop, M. (2010). Gene–environment interactions in 7610 women with breast cancer: prospective evidence from the Million Women Study. The Lancet, 375(9732), 2143-2151.
Fuhrman, B. J., Freedman, D. M., Bhatti, P., Doody, M. M., Fu, Y. P., Chang, S. C., ... & Sigurdson, A. J. (2013). Sunlight, polymorphisms of vitamin D-related genes and risk of breast cancer. Anticancer research, 33(2), 543-551.
