#Literature Review on MTHFR

[mehmetyildizmelbourne-blog]

MTHFR Gene Mutation: Why It Matters & How to Get Tested

Discover the Role of the MTHFR Gene, the Impact of Its Mutations on Your Health, & How You Can Get Tested to Understand Your Genetic Risk Factors You may not have heard of MTHFR, but this enzyme plays a vital role in our body’s ability to process folate (vitamin B9) and maintain your DNA. Related to another critical B vitamin, I recently wrote a story about the global B12 epidemic.  Analyzing…

[gopali]

WEEK 1 ASSIGNMENT

DATA ANALYSIS (WEEK-1)

I chose Gapminder dataset for my analysis as I am interested in understanding the various social or economic issues of humankind and in trying to establish their causes and influences. Gapminder is a non-profit venture that seeks to promote sustainable global development and achievement of the United Nations Millennium Development Goals. Its purpose is to increase the use and understanding of statistics about social, economic, and environmental development at local, national, and global levels.

VARIABLES NAMES

alcconsumption

breastcancerper100TH

Research question: Is Alcohol consumption affects Breast Cancer? Literature Review

The objective of this study was to outline the biological pathways of alcohol-attributable breast cancer, the epidemiological risk relationship between alcohol consumption and breast cancer, and the global burden of breast cancer incidence and mortality attributable to alcohol consumption, with a focus on light drinking. First, the literature regarding the biological mechanisms of how alcohol affects the risk of breast cancer was reviewed and summarized. Second, a search of meta-analyses that evaluated the risk relationship between alcohol consumption and breast cancer was conducted. Last, the burden of alcohol-attributable breast cancer incidence and mortality was estimated by means of a Population-Attributable Fraction methodology. Data on alcohol consumption were obtained from the Global Information System on Alcohol and Health, and data on cancer incidence and mortality were obtained from the GLOBOCAN database. Alcohol consumption affects breast cancer risk through the alteration in hormone levels and the associated biological pathways, the metabolism of ethanol resulting in carcinogens, and the inhibition of the one carbon metabolism pathway. The systematic review found 15 meta-analyses on the risk relationship between alcohol consumption (also light consumption) and the risk of breast cancer. All but 2 of these analyses showed a dose-response relationship between alcohol consumption and the risk of breast cancer. An estimated 144,000 (95% confidence interval [CI]: 88,000 to 200,000) breast cancer cases and 38,000 (95% CI: 2,400 to 53,000) breast cancer deaths globally in 2012 were attributable to alcohol, with 18.8% of these cases and 17.5% of these deaths affecting women who were light alcohol consumers. All levels of evidence showed a risk relationship between alcohol consumption and the risk of breast cancer, even at low levels of consumption. Due to this strong relationship, and to the amount of alcohol consumed globally, the incidence of and mortality from alcohol-attributable breast cancer is large.

Conclusion

Recent publications add to the current body of evidence that consumption of alcoholic beverages is causally associated to cancer of the female breast, even at low levels of alcohol consumption.

Current data indicate that breast cancer risk does not vary by beverage type and strengthen the evidence that ethanol is the main causal factor; nevertheless, other compounds present in various alcoholic beverages may play a role in, or prevent, the development of breast cancer. Polymorphisms in genes involved in the formation and detoxification of ethanol metabolites are known to modulate the risk of cancer at other sites, and could modulate the association of alcohol consumption with breast cancer risk; however, at present, results are controversial and do not allow the identification of susceptibility alleles for breast cancer subtypes. Experimental and epidemiologic studies show that alcohol-induced breast cancer may be related to an enhanced responsiveness to ER, thus suggesting that the association may be stronger for exposure during adolescence and early adulthood. In addition, there is growing evidence of an environmental impact on the breast cancer epigenome through nutrition. The MTHFR polymorphism appears to play a role via a folate-dependent epigenetic mechanism also modified by ethanol and possibly by menopausal status. However, the precise targets of epigenetic deregulation in breast cancer are still unclear; the field is rapidly expanding and additional data may allow the identification of specific methylation signatures. REFERENCES: https://pubmed.ncbi.nlm.nih.gov/27130687/

https://www.sciencedirect.com/science/article/pii/S0749379713006466

[cancersfakianakis1]

Identifying novel genes and biological processes relevant to the development of cancer therapy-induced mucositis: An informative gene network analysis

by Cielito C. Reyes-Gibby, Stephanie C. Melkonian, Jian Wang, Robert K. Yu, Samuel A. Shelburne, Charles Lu, Gary Brandon Gunn, Mark S. Chambers, Ehab Y. Hanna, Sai-Ching J. Yeung, Sanjay Shete

Mucositis is a complex, dose-limiting toxicity of chemotherapy or radiotherapy that leads to painful mouth ulcers, difficulty eating or swallowing, gastrointestinal distress, and reduced quality of life for patients with cancer. Mucositis is most common for those undergoing high-dose chemotherapy and hematopoietic stem cell transplantation and for those being treated for malignancies of the head and neck. Treatment and management of mucositis remain challenging. It is expected that multiple genes are involved in the formation, severity, and persistence of mucositis. We used Ingenuity Pathway Analysis (IPA), a novel network-based approach that integrates complex intracellular and intercellular interactions involved in diseases, to systematically explore the molecular complexity of mucositis. As a first step, we searched the literature to identify genes that harbor or are close to the genetic variants significantly associated with mucositis. Our literature review identified 27 candidate genes, of which ERCC1, XRCC1, and MTHFR were the most frequently studied for mucositis. On the basis of this 27-gene list, we used IPA to generate gene networks for mucositis. The most biologically significant novel molecules identified through IPA analyses included TP53, CTNNB1, MYC, RB1, P38 MAPK, and EP300. Additionally, uracil degradation II (reductive) and thymine degradation pathways (p = 1.06−08) were most significant. Finally, utilizing 66 SNPs within the 8 most connected IPA-derived candidate molecules, we conducted a genetic association study for oral mucositis in the head and neck cancer patients who were treated using chemotherapy and/or radiation therapy (186 head and neck cancer patients with oral mucositis vs. 699 head and neck cancer patients without oral mucositis). The top ranked gene identified through this association analysis was RB1 (rs2227311, p-value = 0.034, odds ratio = 0.67). In conclusion, gene network analysis identified novel molecules and biological processes, including pathways related to inflammation and oxidative stress, that are relevant to mucositis development, thus providing the basis for future studies to improve the management and treatment of mucositis in patients with cancer. http://ift.tt/2sqyBtX