A Promise to a Dying Brother

When I was inducted into the Honor Society in winter 2013, I thought that being on top of my batch will be enough to get me through my journey as a Public Health Ph.D. candidate. Recruiting a dissertation chair is the most challenging so far, especially getting a response from them. What if I do not get a dissertation chair who will be a good match with my dissertation topic? Can I submit my premise and finish my dissertation to another university? A night before my youngest brother passed away; I was on the phone with him. He told me that he is too tired, and I responded that it is okay to let go. He asked me to promise him to go back to school and take on a graduate degree to make a difference. “Promise me that at some point to be involved in a research project that could make a difference to individuals diagnosed with pancreatic cancer.” He passed away in 2007, a few weeks before his 40th birthday, and three months before his only daughter’s first birthday.

Focusing on the impact of cigarette smoking as a factor that promotes pancreatic cancer rather than initiates it will amplify the importance of behavioral change, and enhance the quality of life. The outcome of pancreatic cancer remains dismal, even with treatment combinations of surgery, radiotherapy and chemotherapy with an estimated annual economic burden of $4.9 billion annually (Pandol, Apte, Wilson, Gukovskaya, and Edderkaoui, 2012). Advances in patient management and understanding the biology of pancreatic cancer has taken substantial progress over the years. Herman, Schulick, Hruban and Goggins (2011) found that screening first-degree relatives of individuals with family members affected by pancreatic cancer can identify non-invasive precursors of the disease. In this 2011 study shows the gradual rise in the incidence and number of deaths caused by pancreatic tumors, even with the decline in incidence and mortality of other common cancers. Furthermore, Vincent et al. found that despite developments in detection and management of pancreatic cancer, only about 4% of patients will live five years after diagnosis. Moreover, Vincent et al. (2011) found that present surgical resectioning offers the only chance of cure and improve the survival rate for those with malignant disease localized to the pancreas. Statistical analysis in 2012 study shows 80–85% of patients with advanced unresectable disease responds poorly to most chemotherapeutic agents. Therefore, it is warranted to have continued understanding of the biological mechanisms contributory to the development and progression of pancreatic tumors. On the other hand, Klein et al. (2004) emphasized the significance of quantification of the risk of individuals with a family history of pancreatic cancer as a rational basis for cancer risk screening and counseling. In a prospective registry-based approach of this 2004 study, the risk of these individuals showed an increased risk of developing the disease. Klein et al. (2004) performed standardized incidence ratios and compared the number of incident pancreatic cancers observed with those expected using Surveillance, Epidemiology and End Results (SEER) rates. It was quantified in this registry-based study the pancreatic cancer risk in kindreds with a family member who was diagnosed with the disease, supporting the hypothesis of increased risk in association with family history. While Blackford et al. (2009) failed to identify the signature tobacco-related mutation in cigarette smokers that could have strong implication to the development of pancreatic cancer; this 2009 study found the nonspecific DNA damage caused by tobacco carcinogens. Furthermore, the combined causality of non-tobacco-related mutagenic risk factors such as inherited predisposition to cancer may share mutagenic properties with the tobacco mutagens active in pancreatic tissues (Ding et al., 2008; Prokopczyk et al., 2002). The types and patterns of these mutations provide insight into the mechanisms by which cigarette smoking causes pancreatic cancer (Blackford et al., 2009). Porta et al. (2009) and Blackford et al. (2009) suggested that smoking enhances the risk for pancreatic cancer through mechanisms other than genetic mutation. The development of pancreatic cancer may have a non-significant association to pipe smoking and smokeless tobacco use, but in a large collaborative pooled analysis of non-cigarette tobacco use in 11 studies within the International Pancreatic Cancer Case-Control Consortium (PanC4) found that cigar smoking is associated with an excess risk of the disease (Bertuccio et al., 2011). Cigarette smoking was found to be an established risk factors— both exposure to environmental tobacco smoke (ETS), and active cigarette smoking (Vrieling et al., 2010). Over 40,000 individuals are diagnosed with pancreatic cancer, and less than 5% of patients diagnosed has a survival rate of five years. The component of the smoke of cigarettes that produced in the body as a metabolite of nicotine and the most abundant carcinogens in tobacco smoke is 4-(methyl nitrosamine)-1-(3-pyridyl)-1-butanone (NNK). Vary widely in nicotine content and carcinogenic nicotine metabolites, cigarettes, cigars, and other tobacco products—nicotine reaches the lungs and is quickly absorbed into the bloodstream during smoking. A cigar containing as many as 20 grams of tobacco can have nicotine between 5.9 and 335.2 mg per gram of tobacco (Henningfield, Fant, Radzius, & Frost, 1999). Prokopczyk et al. (2002) noted that the nicotine levels in pancreatic juice in smokers is seven times higher than non-smokers. Blackford et al. (2009) concluded that smokers diagnosed with pancreatic carcinomas harbors more mutations than the non-smoker, therefore, doubles the risk, accounting for 20 to 25% of pancreatic cancers.

Pandol et al. (2012) stated that the pro-carcinogenic effects of smoking on the pancreas are inadequately studied, confirming that tobacco smoking is the strongest avoidable risk and the major environmental factor for pancreatic cancer. Pandol et al. provided valuable insights into the pathogenesis of pancreatic cancer, particularly in the initiation and progression of the disease. Determining the mechanisms underlying the effect of smoking compounds on fibrosis and inflammation will improve our limited knowledge of pancreatic biology. Pancreatic cancer can be classified as genetic, environmental, or both; as well as a disease caused by inherited DNA mutation or mutation by chance. While advances in Genomics gives the promise to early pancreatic cancer detection through better understanding of pancreatic biology, it is paramount to embrace the significance of lifestyle habits that can be modified to evidence-based healthier concepts that translates to reduced cancer risk. Applying lessons learned from the outcome of my proposed study, and existing body of knowledge will prevent the emergence of pancreatic cancer, reduce cancer risk and advance population health. Early behavioral change and interventions will improve the survival rate and quality of life during the time course of pancreatic cancer progression.


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