User:Mwiederman/sandbox

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This is place to practice clicking the "edit" button and practice adding references (via the citation button). Please see Help:My_sandbox or contact User_talk:JenOttawa with any questions.

Link: Project Homepage and Resources


 * Note: Please use your sandbox to submit assignment # 3 by pasting it below. When uploading your improvements to the article talk page please share your exact proposed edit (not the full assignment 3).


 * Talk Page Template: CARL Medical Editing Initiative/Fall 2019/Talk Page Template

Hereditary nonpolyposis colorectal cancer
Topic: Genes Involved: Wikipedia Assignment #2: Literature Search (    /10)

'''1.     How you searched for a source? (    /1)'''

a.      Gene* AND "Lynch syndrome" OR "Hereditary nonpolyposis colorectal cancer" with filters for Review, 10 years, Humans, English

b.     Searched in: Cochrane Reviews (high quality reviews), PubMed (for literature and systematic reviews), Google Scholar (grey literature)

i.     Skimmed abstracts for relevance, credibility, strength, bias, conflict of interest, and appropriateness of source (secondary, well-cited review)

ii. Chose to include "Lynch syndrome" as it is a more appropriate medical term and more commonly used, as supported by “Classification of Tumours” by the World Health Organization that suggests that "Hereditary nonpolyposis colorectal cancer" is outdated and confusing (since Lynch syndrome is a collection of many types of cancer [not just “colorectal cancer” as the original name suggests]). Needed to include the previously used term for completeness.

'''2.     What potential sources were identified and considered? (    /2)'''

a.      Le, S., Ansari, U., Mumtaz, A., Malik, K., Patel, P., Doyle, A., & Khachemoune, A. (2017). Lynch Syndrome and Muir-Torre Syndrome: An update and review on the genetics, epidemiology, and management of two related disorders. Dermatology Online Journal, 23(11).

b.    Chosen: Yurgelun, M. B., & Hampel, H. (2018). Recent Advances in Lynch Syndrome: Diagnosis, Treatment, and Cancer Prevention. ''American Society of Clinical Oncology Educational Book. American Society of Clinical Oncology. Annual Meeting, 38'', 101–109. https://doi.org/10.1200/EDBK_208341

'''3.     Why the source was chosen (what made it better than other choices). (    /2)'''

a.      Specificity to genetics that are practical (i.e. diagnosis) over the other sources (that often focused on measuring genetic changes, but without quantification of their significance or contributions).

b.     Clarity of its definition of Lynch syndrome (encompassing many cancers of the syndrome) and comparing different rates of its included cancers while being focused solely on Lynch syndrome (unlike source a that also includes Muir-Torre syndrome)

'''4.     List why the source that was selected meets Wikipedia’s MEDRS criteria. (    /3)'''

a.      The article is a secondary source, a review which summarizes a broad range of scientific evidence without taking a stance on the evidence, thus providing a balanced and neutral point of view and an understanding of the scientific consensus.

b.     The review is recent, thus including and summarizing much of the new evidence and accurately reflecting current knowledge (i.e. it is published within the last five years [2018]).

c.      The article is not apparently displaying bias, it may be reliable, since it is third-party published (the authors of the review are not directly involved in the studies presented)

d.     The evidence quality is high (i.e., it is a review article and published in a recognised standard textbook by experts in a field, cited by other high-quality papers)

'''5.    How do you plan to use the source for improving the article? (    /2)'''

a.     Our Wikipedia article is currently using care reports and disputed articles in their citations in the related genes section. I plan to use this source to improve the quality of the evidence listing the main clinically relevant genes involved in Lynch Syndrome and reformat the table listing gene involvement. It is important to only write the direct conclusions identified in this article when citing it. Limitations of this article include that its focus on diagnosis means that genes without strong measurement (such as listed in the immunohistochemistry section) do not have direct conclusions drawn, so cannot be used.

Assignment # 3

 * 1) Proposed Changes: I propose the addition of an explanation of the dimerization of the gene products of the 4 main genes involved in Lynch syndrome to clarify the interdependence of the genes involved. I propose the following addition:

The 4 main genes involved in HNPCC normally encode for proteins that form dimers to function:


 * 1) MLH1 protein dimerizes with PMS2 protein to form MutLα, which coordinates the binding of other proteins involved with mismatch repair like DNA helicase, single-stranded-DNA binding-protein (RPA), and DNA polymerases.
 * 2) MSH2 protein dimerizes with MSH6 protein, which identifies mismatches via a sliding clamp model, a protein for scanning for errors.

The impairment of either gene for the protein dimer impairs the protein function. These 4 genes are involved in error correction (mismatch repair), so dysfunction of the genes can lead to the inability to fix DNA replication errors and cause HNPCC.

2. Rationale for proposed change:

a. The previous information was inadequate: The change was suggested to incorporate new information that was currently missing from the Wikipedia article. The Wikipedia article prior to this change makes no mention of dimerization being a function of the genes that are the main cause of HNPCC. This change is significant to the genetics section since the pairing of the gene products clarifies why some genetic mutations are more common and why impairment of either MLH1 or PMS2 leads to the same effect.

b. Further, this addition gives the opportunity to clarity the protein functions (mismatch repair) which explains how impairments in the "error search and repair" machinery leads to cancers (errors and unchecked duplication). These reasons make this addition necessary.

c. Appropriate references were chosen to support the addition: The references chosen to support this section are from reviews found in Assignment 2 to be:


 * 1) Secondary source, a review which summarizes a broad range of scientific evidence without taking a stance on the evidence, thus providing a balanced and neutral point of view and an understanding of the scientific consensus.
 * 2) Recent, thus including and summarizing much of the new evidence and accurately reflecting current knowledge (i.e. it is published within the last five years [2018]).
 * 3) Likely reliable, since it is third-party published (the authors of the review are not directly involved in the studies presented)
 * 4) Of high-quality evidence (i.e., it is a review article and published in a recognized standard textbook by experts in a field, cited by other high-quality papers)
 * 5) Specific, with a chosen citation used to support only one claim. Citations are used to substantiate every claim such that none are interpretations or opinions of the literature.

3. Controversy:

a. Any controversy about the addition of these sentences to the genetics is that this is not likely related to “Lynch syndrome” but would likely be related to inclusion of new potentially excessive or confusing information. Specifically, it is not that the function of these genes is important to Lynch syndrome – whether knowing of not how they function their dysfunction is the same and leads to the cancer.


 * 1) However, I rebuttal that this is a fuller picture of the underlying genetics that we currently know. I chose to include this because it creates a more clear relation between all of the known genes and explains why we suppose that cancer arises with each mutation.

b. Controversy may arise that this addition complicates the story of autosomal dominance, mentioned elsewhere in the Wikipedia article. Both the autosomal dominant inheritance and the above proposed addition are correct, however, it may be construed that they conflict as dimerization and multiple gene involvement makes for more complicated genetic cause.


 * 1) However, I rebuttal that these two pieces of information are not mutually exclusive and that inheritance of the genes whose protein products dimerize is just a more full picture of the pathway.

4. Critique of Source:

a. There is the possibility for bias within the used citations. Most notably, the citation is a review (not systematic review) that only covers published literature and with no defined (variable and not all encompassing) search methods and so experience potential for a publication or search/selection bias. Specifically, we know that there is positive results publication bias, so this may have affected the results. I could create a funnel plot to assess for missing literature were the raw data provided, but that is not the case here, deepening my concern for bias. Secondly, in searching the literature without a defined method, it would be easier to miss a body of work. Additionally, without defined search methods, grey literature is often excluded.


 * 1) How I have adapted my path based on the potential for citation biases: I have verified that the review has come to the same conclusion as a few others, lowering the potential that the bias changed the conclusion. Rather, I suggest that it is simply not all encompassing – it is likely that not all genes involved in Lynch syndrome are covered in this paper. There exists within the Wikipedia page a nod to lesser known genes, so I believe this sufficient to add to the narrative and have considered bias when using my chosen articles.

b. Given that I have chosen a review article for my source, there was no evidence quality appraisal done to verify that only high quality evidence was used to draw conclusions. This may lead to confounding bias if merged trials are unequal and low quality.


 * 1) How I have adapted my path based on the potential for citation biases: I went back to read a portion of the original citations made by the review article to assess their validity to determine if this review article was using high quality evidence.