The Journal of Science Extension Research – Vol. 3, 2024
Are there any associations between an individual’s genetic information and the incidence rate of developing PAC? Clinical Practice Guidelines in Oncology (Tempero 2010 et al) reported that 5-10% of PAC cases arise from a genetic vulnerability. It is still with major uncertainty that contemporary research can account for the majority of PC associated germline mutations. A lack of known pathogenic mutations suggests further unnamed mutations. These findings mean that up to 1 in 5 people with PAC are able to receive an earlier diagnosis therefore improving their prognosis dramatically when compared to the average diagnosis timeframe. One study (Hu et al. 2018b) took a population of 1,819 individuals with PC from a larger group of 140,000 who underwent multigene panel testing. This study found that 97.7% of PC’s were PAC’s. The study reported that 20.73% (combined frequency) of all patients carried at least one type of genetic mutation relating to the onset of this particular cancer. What deleterious germline mutations are linked with PAC? Knowing there is an association between PC and inherited germline mutations, research is now directed towards finding the specific deleterious germline mutations responsible for the onset of PC. Deleterious germline mutations escalate one’s predisposition to certain disorders, diseases, and syndromes. Genes that influence tumour suppression pose an increased risk of cancer if mutated, damaged, or missing. The study found that 5.5% of PC patients carried mutations in 6 genes linked with PC. Limitations to this data include the usage of public reference controls, the fact that the panel of 21 genes did not represent all deleterious germline mutations associated with cancer, and the geographical location cases came from restricted areas therefore not accurately
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representing all races regarding the data collected. In another study (Salo-Mullen 2015 et al). Again, the genes BRAC2 and BRAC1 were found to be the most common mutation, along with the presence of 22 other mutations found to be associated with PC and its related syndromes. The study acknowledged its limitations, the main being a patient selection bias during recruitment and testing, that being said, the population was one of the largest current published studies in its area, giving real-world depictions and applicable data. The most prevalent of these deleterious genes was BRAC2 (BReast CAncer gene 2). Upon further examination, the BRCA1 and BRCA2 gene mutations were found to have higher recorded prevalence rates in the Ashkenazi Jewish (AJ) race. The AJ population in each study has consistently recorded higher risk ratios, cases of PC, and, consequentially, cases of familial PC along with mutations in the BRCA genes. For instance, PAC patients with positive family history as well as AJ heritage had a BRCA1/2 mutation prevalence of 13.7%, this figure is extremely high when compared to patients with no family history or AJ heritage with a mutation prevalence rounded to 0%. How do these specific mutations relate to PAC in terms of familial heredity? Familial history is another tool that can be used to estimate an individual’s risk of developing PC. Though we do not yet understand the reasons why certain groups of people are more likely to carry specific mutations, we can recognise and apply the patterns we are presented with and can use this information to aid the current forms of treatment and research concerning PC. In a study focused on familial PC (Shi, Hruban & Klein 2009), it was stated that 5-10% of all patients with PC had a positive family history. This data supports links between inherited
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