Neo-Confucianism Is a Philosophy Which Was Born TEST1 Research Paper

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Breast Cancer

How Genes Influence Breast Cancer

Director of the National Cancer Institute

How Genes Influence Breast Cancer

Many environmental factors can affect a person's risk of breast cancer, but they are not the only issues to consider. Genetics also play a strong role in whether a person develops breast cancer or avoids it. A strong family history of the disease can predispose a person to breast cancer, but it is not a guarantee that the person will acquire the disease. Conversely, people with no family history have also contracted breast cancer, so genetics are not the only issue. They are merely a part of the puzzle. The research here indicates that genetics may be a larger part of the puzzle than first thought, however, and proposes recommendations to spend more time and financial resources on discovering the significance of genes and how they influence breast cancer. Recommendations for action include more funding to isolate specific gene markers that may be linked to breast cancer, and further research into how these genes work with other genes to produce the disease in specific patients.

Introduction

Research into the link between genetics and breast cancer has indicated that specific genes may be at fault when it comes to whether a person contracts the disease or avoids it. Although there are other factors, it is this gene research on which this paper will focus. Because genetics, unlike environmental factors, cannot be controlled or changed, those who are most likely to contract breast cancer through genetic issues are those who are most at risk and unable to control that risk. To that end, there are recommendations to be made. These include:

Further research into the relationship between genes and breast cancer.

Isolating the specific genes that cause breast cancer and determining how they work in conjunction with others to produce breast cancer.

Funding for genetic testing for those who may be at the highest risk for breast cancer.

Funding for the issue of genes and breast cancer, in order to save more lives every year.

Review of the Literature

DNA Repair

Reviewing the literature on this issue is vital. It is here that research that has been conducted by others can be examined and cited to show what is being discovered regarding the APE1 gene and breast cancer. It is believed that there is a strong genetic susceptibility to environmental diseases, including cancer, that can be used to determine why one person develops breast cancer and another does not. Many patients who have breast cancer have surgery, but there are also radiation and chemotherapy options to consider, both of which can have serious side effects (Chang-Claude, et al., 4803). Finding a way to stop breast cancer and also to determine who is most susceptible to it can help individuals prepare for what medical interventions they may need in the future. Currently, the strongest and most significant areas of research focus on polymorphisms in DNA (Harms, 74).

This research has indicated that repair genes are a vital component of the equation when determining susceptibility in breast cancer patients because of their capacity to repair DNA, which is critical for preventing cancer and protecting the genome (Harms, 74). Zhao, et al. studied the breast cancer and genetics link in order to determine if it was specific to any particular population. Their findings were based on the understanding that it has long been believed there is a mix of genetic and environmental factors at play when it comes to the development of breast cancer (Zhao, et al.). Genetic abnormalities in the genes can result in being much more susceptible to breast cancer (Zhao, et al.). However, it is not actually that the gene abnormalities cause the cancer, but that the genes are unable to properly repair the damage that is done to the DNA by other factors, which makes the person more likely to contract a malignancy (Zhao, et al.).

The systems that work to repair human DNA play a highly significant role when it comes to the protection of the genome from harm through environmental and endogenous factors (Wood, et al.). The genetic variations that are seen in DNA repair genes cause the DNA repair function to be altered (Wu, 1). This results in DNA damage that continues to accumulate, and when enough damage has occurred there is cell apoptosis (unregulated growth) which can develop into cancer (Wu, 1). It is possible for cell growth to occur without the presence of cancer, but the damage to the DNA is also a contributing factor (Wu, 1). There are specific variations in both DNA damage and repair that have been closely linked to the susceptibility of breast cancer in an individual (Wu, 1). This highlights the importance of the damage and repair issues as they relate to DNA when it comes to whether a person will develop breast cancer (Wu, 1).

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There are some DNA repair systems that are more significant than others when it comes to the risk of breast cancer, such as the base excision repair (BER). It is one of the main pathways that is responsible for repairing single strand breaks and base damage in DNA, and has been associated with a risk of cancer (Wu, 1). In other words, if the BER is not working correctly, it is more likely that DNA will not be able to be repaired properly. That will lead to a higher risk for cancer to develop, but will not necessarily indicate that a person will definitely get cancer (Wu, 1).

In the BER process, there is a rate limiting enzyme -- the APE1 gene -- that is responsible for repairing DNA and protecting against both exogenous and endogenous agents (Wu, 1). When the APE1 gene fails or does not work correctly through a mutation or other problem, there is less protection and fewer repairs made to the DNA (Wu, 1). That can lead to the growth and development of breast cancer. Because APE1 is such an important protein for DNA repair in the BER pathway, it initiates repair of single strand breaks in the DNA through phosphodiesterase (Kang, 97). The genetic polymorphisms that occur in genes that facilitate DNA repair influence how susceptible a person is to a number of cancers (Goode, 2002; Smith, 2003; cited in Kang, 97).

There have been a number of epidemiological studies that have shown a link between genetic polymorphisms in APE1 and a higher risk of cancer (Cao, 2011; Gu, 2009; cited in Kang, 97). Additionally, Poletto, et al. used the APE1 gene to study acetylation in specimens of triple negative breast cancer (pg. 37). Cao, et al. also studied the Asian population, with a specific focus on the Chinese (pg. 863). The goal was to determine whether that group had a larger risk of abnormal APE1 genes or whether being Asian was not a risk factor or marker for that particular abnormality. Notably, it is not only Cao, et al. who studied Chinese individuals and their cancer risk based on the APE1 gene. While Cao, et al. studied this gene in relation to renal cell carcinoma, Kang, et al. studied the gene in specific relation to breast cancer. During that study, Kang, et al. discovered a correlation between the APE1 gene and the development of breast cancer in the Chinese population (pg. 98).

APE1 1349 T>G polymorphism

Gu (2009) used a meta-analysis and reported that the APE1 1349 T>G polymorphism was a low risk factor for the development of cancer (Kang, 99). That experiment indicated that G. allele could be a risk for some types of cancer, but not for breast, lung, or bladder cancer (Gu, 510). A number of studies have been conducted to look at the association APE1 T1349G polymorphism and cancer in various countries, but there have been only inconclusive results (Gu, 510). Gu's (2009) meta-analysis, though, is suggestive of the idea that the APE1 T1349G polymorphism could be a contributing factor to genetic susceptibility for cancer.

More studies will need to be conducted, since not all agree. For example, a study done by Zhou indicated that APE1 1349 T>G polymorphism was not seen in the increased risk of cancer from the standpoint of genetic susceptibility (Kang, 99). Other studies have shown that there is no significant association between the APE1 1349 T>G polymorphism and cancer of the breast (Kang, 99). That has been reported in many studies, as the results have been consistent with regard to the APE1 1349 T>G polymorphism and how it is not likely to be a factor when it comes to breast cancer susceptibility (Kang, 99).

APE1 -656 T>G polymorphism

At this point, there is still a lack of studies that clearly investigate the role of -656 T>G polymorphism as it relates to breast cancer (Kang, 100). There are variants of genotypes that have been associated with lower lung cancer risk, and these studies have shown that the -656 G. allele had transcriptional activity that was much higher than the APE1 -656 T. allele….....

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