Category Archives: Epidemiology

Bridging Cancer Epidemiology and Social Evolution

Research Design 2Modern epidemiology is a direct result of the paradigm shift from a population-based (upstream) to a downstream (individual) approach. The impact of modern epidemiology such as ‘molecular’ and ‘genetic’ epidemiology (Loomis & Wing, 1990; Diez-Roux, 1998) requires an explanatory power that mostly dependent upon the advances in technology and information systems. Moreover, before estimating the economic effect of a specific intervention before it is implemented, nor assess the economic and/or quality-of-life value of an ongoing or anticipated intervention (Rothermel, 2013); it is critical to recognize not only the significance of sophisticated technologies that go beyond the established genome, proteome, and gene expression platforms, but also new techniques of study design and data analysis (Pearce, 1996; Verma, Khoury & Ioannidis, 2013). Given the remarkable progress in the last decade in advanced technology and new methods for biologic measurements, the reductionist approach of modern epidemiology often ignored the significant causes of disease. Pearce (1996) argue that epidemiology must reintegrate itself into public health and must rediscover the population perspective. However, while the new paradigm could produce a lifestyle approach to social policy, the cumulative outcome of research in cancer epidemiology could equate positive implications to population health.

The key figures in the new epidemiologic model not only acknowledges the development of new techniques of study design and data analysis but also recognize the need for a multidisciplinary approach (social, biologic, statistical), and specifying the population group as the unit of study (Susser, 1985). While occupational carcinogens can be controlled with some difficulty through regulatory measures (Pearce, 1996), it is essential to acknowledge the fundamental problem of tobacco use, not by its consumption but in its production. Pearch (1996) focused on some of these fundamental changes in epidemiology over the past few decades and considered the concepts of causality involved, as well as their ideological and practical consequences. While smoking cessation could be the probable social implication, it is important to stress the epidemiologic value of a study on the apparent correlation between gender and age, modification effect of tobacco use among individuals with pancreatic cancer (PC) and cancer types with a shared-gene association (CTSG-A). The outcome of a risk factor epidemiologic study in individual terms could uplift precision medicine to meet the challenges in tailoring medical interventions based on patient’s biological profile, genetic and epigenetic traits, giving a better understanding of the environment, genetic, biodemographic interactions (EGBIs).

Embraced by both biomedical and social determinist frameworks, the interlinking of the traditional epidemiologic level of intervention (upstream or distal) and the modern epidemiologic level of intervention (downstream or proximal) put public health in the conundrum of the proximal-distal divide. Signal the importance of the argument of the 2008 study of Krieger in replacing the terms proximal and distal from the public health lexicon, supports the recommendation of Wemrell et al. (2016) on the critical need for open interdisciplinary debates on the contribution of social theory to the epidemiological inquiry. While coping with the demand of the 21st-century, global health could still be viewed and approached within the mindset of traditional epidemiology, and the purview of molecular and cancer epidemiology.

The discovery of tobacco smoking as a cause of lung cancer in the early 1950s gave the field of epidemiology its recognition (Pearce, 1996), shifting the epidemiologic paradigm in the object of study in the mid-20th century on the role of multiple causes. Establishing the correlation of age, gender a modifiable risk factor (smoking) with PC and CTSG-A requires the use of early and current epidemiologic theories, and contemporary mainstream epidemiologic concept coalescing to a United Paradigm of Cancer Causation (UPCC). The complex, integrative approach of UPCC supports the views of Loomis, and Wing (1990), Pearce (1996), and McEwen and Getz (2013) in embracing the new epidemiologic paradigm congruent to the advances in cancer genome sequencing. Theorizing the pathopoiesis mechanism of smoking, inherited genes, and association of gender and age in the etiopathogenesis of PC/CTSG-A warrants exploration of its causal footprints, conjoining both biomedical and lifestyle (Krieger, 2011).

Follow-up and future research on the role of molecular epidemiology in emphasizing individual susceptibility to PC will assess the relative contribution of modifiable risk factors to non-modifiable genetic factors. In this premise, the etiopathogenesis of the disease could be explored from the bottom up. Bridging cancer epidemiology and social evolution will be dependent upon the incorporation of the strength of the social network and social contagion theory. The testable assumption of the social network theory as its strength states that the social structure of the network itself be primarily responsible for determining individual behavior and attitudes by shaping the flow of resources which determines access to opportunities and constraints on behavior (Berkman et al., 2000). Why choose if a single theory cannot make a change? Incorporating these ideas in addition to the composite and underpinnings of UPCC could springboard a priori argument on the role of social networks in the spread of an intervention such as smoking cessation, or amplifying the promotion of the significance of early screening to improve mortality and morbidity.

While the causal nature of peer effects could be associated with tobacco use; the social contagion theory of Christakis and Fowler (2013) set an argument on human social networks exhibiting a “three degrees of separation.” Such association could support the assumption of spreading the interpersonal influence that acknowledges the significance of early screening, and the promise of a novel therapeutic approach. Like the widely discussed classic paper of Travers and Milgram (1969) on ‘six degrees of separation,’ the three degrees of separation or the three degrees of separation rule (Christakis & Fowler, 2009) agreed on the premise that telegraph phrases are meant to be evocative, and not definitive. For example, the role of interpersonal influence in spreading novel ideas such as advances in early screening to achieve a more significant therapeutic outcome. The preponderance of the evidence that points to the added significance of a passive-broadcast viral messaging to create social contagion warrants the recognition of the approach. Taking into account factors such as the promise of the outcome of a research study in the quality of life, social and economic incentives could expand the social network and amplify social support needed by individuals with PC or any deadly diseases. According to Kroenke et al. (2013), effective social support interventions need to evolve beyond social-emotional interventions and need to account for disease severity and treatment status.

References

Berkman, L. F., Glass, T., Brissette, I., & Seeman, T. E. (2000). From social integration to health: Durkheim in the new millennium. Social Science & Medicine51(6), 843-857. https://doi.org/10.1016/S0277-9536(00)00065-4

Christakis, N.A & Fowler, J.H. (2009). Connected: The Surprising Power of Our Social Networks and How They Shape Our Lives. (First ed.). New York: Little, Brown, and Company.

Christakis, N. A., & Fowler, J. H. (2013). Social contagion theory: examining dynamic social networks and human behavior. Statistics in medicine32(4), 556-577. doi: 10.1002/sim.5408

Diez-Roux, A. V. (1998). On genes, individuals, society, and epidemiology. American Journal of Epidemiology148(11), 1027-1032. http://dx.doi.org/10.1093/oxfordjournals.aje.a009578

Krieger, N. (2008). Proximal, Distal, and the Politics of Causation: What’s Level Got to Do With It?  American Journal of Public Health (AJPH), 98(2). http://dx.doi.org/10.2105/AJPH.2007.111278

Krieger, N. (2011). Epidemiology and the people’s health: theory and context (Vol. 213). New York: Oxford University Press.

Kroenke, C. H., Kwan, M. L., Neugut, A. I., Ergas, I. J., Wright, J. D., Caan, B. J., … & Kushi, L. H. (2013). Social networks, social support mechanisms, and quality of life after breast cancer diagnosis. Breast cancer research and treatment139(2), 515-527. doi:  10.1007/s10549-013-2477-2

Labilles, U. (2015a). Reevaluating the Impact of Cigarette Smoking on Pancreatic Cancer. Unpublished manuscript, College of Health Sciences, Public Health, Epidemiology, Walden University, Minneapolis.

Labilles, U. (2015b, September 27). A Promise to a Dying Brother [Web log post]. Retrieved from https://onenationsecho.com/2015/09/27/a-promised-to-a-dying-brother/.

Labilles, U. (2015c). Prospectus: Tobacco Use and Family Cancer History in the Pathopoiesis of Pancreatic Cancer. Unpublished manuscript, College of Health Sciences, Public Health, Epidemiology, Walden University, Minneapolis.

Labilles, U. (2016). The New Public Health: Beyond Genetics and Social Inequalities. Unpublished manuscript, College of Health Sciences, Public Health, Epidemiology, Walden University, Minneapolis.

Labilles, U. (2017). Pathopoiesis Mechanism of Smoking and Shared Genes in Pancreatic Cancer. ProQuest-CSA, LLC. Library of Congress, Copyright R# TX 8-490-984, Washington DC. doi: 10.13140/RG.2.2.30721.35681

Loomis, D., & Wing, S. (1990). Is molecular epidemiology a germ theory for the end of the twentieth century?. International journal of epidemiology, 19(1), 1-3. http://dx.doi.org/10.1093/ije/19.1.1

McEwen, B. S., & Getz, L. (2013). Lifetime experiences, the brain, and personalized medicine: An integrative perspective. Metabolism62, S20-S26. https://doi.org/10.1016/j.metabol.2012.08.020

Pearce, N. (1996). Traditional epidemiology, modern epidemiology, and public health. American journal of public health86(5), 678-683.

Rothermel, C. (2013). What is health economics and outcomes research? A primer for medical writers. AMWA Journal, 28(3)

Susser, M. (1985). Epidemiology in the United States after World War II: the evolution of technique. Epidemiologic reviews7(1), 147-177. http://dx.doi.org/10.1093/oxfordjournals.epirev.a036280

Travers, J., & Milgram, S. (1969). An experimental study of the small world problem. Sociometry, 425-443. doi: 10.2307/2786545

Verma, M., Khoury, M. J., & Ioannidis, J. P. (2013). Opportunities and challenges for selected emerging technologies in cancer epidemiology: mitochondrial, epigenomic, metabolomic, and telomerase profiling. Cancer Epidemiology Biomarkers & Prevention22(2), 189-200. http://dx.doi.org/10.1158/1055-9965.EPI-12-1263

Wemrell, M., Merlo, J., Mulinari, S., & Hornborg, A. C. (2016). Contemporary epidemiology: a review of critical discussions within the discipline and a call for further dialogue with social theory. Sociology Compass10(2), 153-171. doi: 10.1111/soc4.12345

 

From an Evolutionary Model to the Unified Paradigm of Cancer Causation (UPCC)

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Three essential events launched the field of cancer epidemiology during the 18th century. First, is Bernardino Ramazzini’s study on cervical cancer in 1713, the research of Percival Pott in 1775 that led the way on occupational carcinogenic exposure studies, and Thomas Venner on the danger of tobacco use in his Via Recta, published in London in 1620 (American Cancer Society, 2014). After two centuries when John Hill wrote a book entitled “Cautions Against the Immoderate Use of Snuff” in 1761; Krain (1970), along with other studies in the 1970s, Wynder, Mabuchi, Maruchi and Fortner (1973) explored the causality of tobacco use in the development of PC. Jones et al. (2008) found that PCs have an average of 63 genetic alterations that can explain the major features of pancreatic tumorigenesis. The intensive genetic studies described by Jones et al. (2008) gave way to the better understanding of the core set of pathways and processes, embracing the idea of Owens, Coffey, and Baylin (1982) that tumor heterogeneity is a fundamental facet of all solid tumors. While pancreatic cancer (PC) has few viable treatment options, Jones et al. (2008) suggested that the best hope for therapeutic development may lie in the discovery of agents that target the physiologic effects of the altered pathways and processes rather than their gene components. Above all, the significance that could not have been appreciated in the absence of global analysis is the identification of the precise genetic alterations that may be responsible for tumor pathway dysregulation (Jones et al., 2008).

The pathogenic theory of medicine or the germ theory of disease was highly controversial when first proposed as a concept that microorganisms are the cause of many diseases. After validation in the 19th century, germ theory revolutionized both medical thought and the art of surgery, becoming a fundamental part of modern medicine and clinical microbiology. My metatheory, the “Unified Paradigm of Cancer Causation (UPCC)” is as a composite of germ theory and Darwinian evolutionary system (Greaves & Maley, 2012) along with other theories will provide clarity on the narrative of the initiation of PC. Albeit the acceptance of the somatic mutation theory of carcinogenesis (SMT) as the mainstream narrative of how neoplasms develop (Soto & Sonnenschein, 2004), SMT included in the UPCC’s cocktail of theories will build on the arguments of the core principle of genetic variation and pattern of mutations (environmental and genetics) that are sufficient probable causes of the disease. UPCC could explain the behavior of PC cell in rationalizing the complex array of the possible interaction of smoking and inherited genes.

Pancreatic cancer is the fourth most prevalent cause of cancer death in Western societies and is projected to be the second leading cause within a decade (Waddell et al., 2015). While using the Darwinian methods that link human sociocultural progress to genetic evolution (Richerson & Boyd, 2000); Lynch and Rebbeck (2013) used a “Multi-level Biologic and Social Integrative Construct” (MBASIC) to integrate macro environment and individual factors with biology. Considering the limitation and information generated by single-level studies have reached a saturation point (Lynch & Rebbeck, 2013), I highlighted the significance of individual level (behaviors, carcinogenic exposures); and biologic level (inherited susceptibility variants in my dissertation “Pathopoiesis Mechanism of Smoking and Shared Genes in Pancreatic Cancer.” Germline changes associated with PC could range from slightly increased risk (low penetrance genes) to high lifetime risk (high penetrance genes). Given that PC is the antecedent of inherited (germline), and acquired (somatic) mutations in cancer-causing genes, adding the probable correlation between gender and age, modifiable risk factors to the equation that could trigger or wake up a sleeping germline mutation could position the result of a study for improved public health intervention, translation, and implementation in clinical settings to alter the expression of the disease.

References

American Cancer Society. (2014). History of cancer epidemiology. Retrieved from http://www.cancer.org/cancer/cancerbasics/thehistoryofcancer/the-history-of-cancer-cancer-epidemiology

Greaves, M., & Maley, C. C. (2012). Clonal evolution in cancer. Nature, 481(7381), 306-313. doi: 10.1038/nature10762

Hill, J. (1761). Cautions Against the Immoderate Use of Snuff: Founded on the Known Qualities of the Tobacco Plant and the Effects It Must Produce When This Way Taken into the Body. R. Baldwin and J. Jackson, London, UK. (Held now only as a self-contained pamphlet at shelfmark 1560/2918 in the British Library).

Jones, S., Hruban, R. H., Kamiyama, M., Borges, M., Zhang, X., Parsons, D. W., … & Iacobuzio-Donahue, C. A. (2009). Exomic sequencing identifies PALB2 as a pancreatic cancer susceptibility gene. Science324(5924), 217-217. doi: 10.1126/science.1171202

Krain, L. S. (1970). The rising incidence of carcinoma of the pancreas—real or apparent?. Journal of surgical oncology2(2), 115-124. doi: 10.1002/jso.2930020206

Labilles, U. (2015a). Reevaluating the Impact of Cigarette Smoking on Pancreatic Cancer. Unpublished manuscript, College of Health Sciences, Public Health, Epidemiology, Walden University, Minneapolis.

Labilles, U. (2015b, September 27). A Promise to a Dying Brother [Web log post]. Retrieved from https://onenationsecho.com/2015/09/27/a-promised-to-a-dying-brother/.

Labilles, U. (2015c). Prospectus: Tobacco Use and Family Cancer History in the Pathopoiesis of Pancreatic Cancer. Unpublished manuscript, College of Health Sciences, Public Health, Epidemiology, Walden University, Minneapolis.

Labilles, U. (2016). The New Public Health: Beyond Genetics and Social Inequalities. Unpublished manuscript, College of Health Sciences, Public Health, Epidemiology, Walden University, Minneapolis.

Labilles, U. (2017). Pathopoiesis Mechanism of Smoking and Shared Genes in Pancreatic Cancer. ProQuest-CSA, LLC. Library of Congress, Copyright R# TX 8-490-984, Washington DC. doi: 10.13140/RG.2.2.30721.35681

Lynch, S. M., & Rebbeck, T. R. (2013). Bridging the gap between biologic, individual, and macroenvironmental factors in cancer: a multilevel approach. Cancer Epidemiology Biomarkers & Prevention22(4), 485-495. doi: 10.1158/1055-9965.EPI-13-0010

Owens, A.H., Coffey, D.S. & Baylin, S.B. (1982). Tumor cell heterogeneity: Origins and Implications. (Vol 4). San Diego: Academic Press.

Richerson, P. J., & Boyd, R. (2000). Evolution: The Darwinian theory of social change: an homage to Donald T. Campbell. Paradigms of Social Change: Modernization, Development, Transformation, Evolution, pp. 1-30. http://www.des.ucdavis.edu/faculty/richerson/evolutionberlin.pdf

Richerson, P. J., Boyd, R., & Henrich, J. (2010). Gene-culture coevolution in the age of genomics. Proceedings of the National Academy of Sciences, 107(Supplement 2), 8985-8992. doi: 10.1073/pnas.0914631107

Soto, A. M., & Sonnenschein, C. (2004). The somatic mutation theory of cancer: growing problems with the paradigm?. Bioessays26(10), 1097-1107. doi: 10.1002/bies.20087

Waddell, N., Pajic, M., Patch, A. M., Chang, D. K., Kassahn, K. S., Bailey, P., … & Quinn, M. C. (2015). Whole genomes redefine the mutational landscape of pancreatic cancer. Nature518(7540), 495-501. doi: 10.1038/nature14169

Wynder, E. L., Mabuchi, K., Maruchi, N., & Fortner, J. G. (1973). Epidemiology of cancer of the pancreas. Journal of the National Cancer Institute50(3), 645-667. https://doi.org/10.1093/jnci/50.3.645

 

Continuing the Journey to Make a Difference

Innovative Management and Development (Inno MD) from Uly Labilles, DMD, Ph.D on Vimeo.

An Executive Summary

Screenshot (94)Pathopoiesis Mechanism of Smoking and Shared Genes in Pancreatic Cancer

DOI: 10.13140/RG.2.2.33028.63362

To raise new questions, new possibilities, to regard old problems from a new angle requires creative imagination and marks the real advance in science (Einstein & Infeld, 1938, p. 92).

Pancreatic cancer (PC) at the start of the 21st century continues to be a vital unresolved health problem, remaining as one of the deadliest human cancers. By the year 2030, it is projected that PC will be the second leading cause of cancer death after lung cancer among the major types of cancer (Rahib et al. 2014). The outcome of this study would provide valuable insights into the etiopathogenesis of PC and cancer types with a shared-gene association (CTSG-A), as well as the possible recognition of the probable unique pattern of PC malignancy among defined age groups, between men and women, in correlation to the modification effect of smoking to cancer predisposition genes (CPG), or its combined impact. Additional understanding of the pathopoiesis dynamics of smoking status, gender, and age in individuals with CPG in the induction and promotion of PC could help promote pre- and post behavioral diagnosis change. This study may assist in developing a novel patient management approach to accurately assess the disease burden under the lens of public health and modern epidemiology. Although genetic changes can be either somatic or hereditary, described as de novo (new), PC does not arise de novo (Maitra & Hruban, 2008), but rather initiated by a probable gene mutation such as p16/CDKN2A that results to debilitating metabolic effects of uncontrolled growth. Given the assumption that a disease is caused by a factor that can be controlled, exploring the relationship between modifiable health behaviors such as smoking and family cancer history (FCH), CPG or shared genes was a legitimate endeavor. In this study, genetic syndromes associated with PC were interchangeably referred to as FCH, CPG, or shared genes. Pancreatic cancer and other cancers found to have a shared-gene association (S-GA) were the dependent variables, and smoking status, age, and gender were the independent variables; this study addressed the following research questions (RQs) and hypotheses:

RQ1: Is cigarette smoking associated with the etiopathogenesis of pancreatic cancer and cancer types with shared gene association (CTSG-A)?

H01: Smoking level has no correlation with prevalence of PC and CTSG-A.

H1: Smoking can increase the risk of PC and CTSG-A.

RQ2: Is there a relationship between the combined role of age and gender in the etiopathogenesis of PC and CTSG-A?

H02: Age and gender have no correlation with prevalence of PC and CTSG-A.

H2: Age and gender are correlated with the prevalence of PC and CTSG-A.

The unique contribution of this dissertation to the current body of knowledge involved examining the links between tobacco use, gender, age, PC, and shared genes. This dissertation could promote population health, and lessons learned could reshape the current understanding of cancer epidemiology by providing the scientific justification for the implementation of screening, surveillance, and education programs. The outcome of this dissertation would fit into the practical intervention approach of adopting a healthy lifestyle such as smoking cessation as part of positive, meaningful social change to improve prognosis and quality of life during PC progression.

Background

Pandol et al. (2012) noted the economic burden of PC with an expected yearly cost of $4.9 billion and underscored the significance of determining the mechanisms underlying the effect of smoking compounds that may provide additional insights into the pathogenesis of the disease. The investigation gave valuable insights into the etiopathogenesis of pancreatic growth from its induction and promotion. Moreover,  findings of Hart, Kennedy, and Harvey (2008); and Schenk et al. (2001) support the unique probable contribution of this dissertation to the existing body of knowledge, generating a snapshot of a possible correlation of smoking, gender, and age to the development of PC and CTSG-A, enhancing the knowledge on the pathopoiesis mechanism of these predictors in disease induction and promotion. The plethora of findings of the past and present studies highlighted the causal significance of modifiable risk factors and genetics in the pathosis of PC. The goal of these studies falls largely within the confines of understanding the insights of genetic alterations and specific modifiable risk factors. Much of the recent research concentrates in this line of inquiry; therefore, recognizing the modifying effect of smoking to individuals with family aggregation justifies the merit of this dissertation and future endeavors.

Blackford et al. (2009) noted that previous researchers overlooked the distinction between the passenger and driver mutations that explains the often unconvincing associations between smoking and driver mutations. Recognizing this gap, and while there are continued studies on different aspects of the PC genomic landscape, this dissertation intends to provide a descriptive analysis of the prevalence pattern of PC and CTSG-A known to have increased risk of extrapancreatic malignancies versus nonsmokers. The mechanisms through which smoking, gender, age, and CPG affect PC remain unknown, making it critical to explore the role of these three predictors in the disease clustering to develop a more efficient management and clinical approach. With an exhaustive understanding of the patterns of somatic alteration in pancreatic carcinogenesis comes the opportunity to understand the influence of these factors on metastatic progression (Yachida & Iacobuzio-Donahue, 2013). The burden of chronic diseases such as PC is often neglected on the public agendas. The increasing annual economic burden of PC is beyond genetics and social inequalities, making it necessary to embrace the shift in the level of analysis from traditional to modern epidemiologic and New Public Health approach. The significance of the successful delivery of the New Public Health both at the level of society and individual behavior (Halpin et al., 2010) justifies the intent of this dissertation on the need for further exploration of the pathopoiesis mechanism of tobacco use and FCH, the etiopathogenic role of gender and age. The unveiling of the “Precision Medicine Initiative” during the State of the Union Address of President Barack Obama on January 20, 2015, springboard the new effort of revolutionizing a new model of patient-powered research that could accelerate biomedical discoveries and provide clinicians with new tools, knowledge, and therapies. New research directions are warranted to reverse the lethal outcome of this disease.

Study Design and Approach

The causality of tobacco-related mutagenic risk factors and the correlation between gender and age and CPG will not only raise awareness of the significance of cancer risk screening and counseling but will also increase the understanding of environmental, genetic, and biodemographic interaction (EGBI) contributing to the development and progression of PC. The results of this study may be used to promote lifestyle change in reducing cancer risk. Improving the perceived corollary of individuals with inherited genes and quality of life during the expression or final stage of the disease is dependent on the favorable adjustment of behavioral risk factors. This study intended to explore the association between smoking, gender, and age in individuals with CPG. I used a cross-sectional design to determine the prevalence of pancreatic cancer and CTSG-A among smokers and non-smokers.  The potential association of smoking, gender, and age as predictors of the outcome variable (PC/CTSG-A) were explored using a cross-sectional design. Secondary data were recoded and randomized using IBM Statistical Package for the Social Sciences (SPSS, Version 23, 64-bit edition). Although logistic regression makes no assumptions about the distributions of the predictor variables (smoking, gender, age), ordinal modeling was the fundamental property of the design of this study to test whether smoking level and age are effect modifiers to inherited genes or combined causative predictors in the induction and promotion of PC and CTSG-A.

The population for the study was defined as participants of the Behavioral Risk Factor Surveillance System (BRFSS) survey. Subject selection criteria were set narrowly, by selecting specifically those who smoke and do not smoke with PC/CTSG-A (survivorship module), versus non-smokers with PC/CTSG-A. Association between smoking, age, gender, PC, and PC/CTSG-A are explored using hypothetical conceptual cohort. A hypothetical conceptual cohort is defined as participants from the 2014 BRFSS survey who qualified as high-risk based on the level of smoking. The dependent variable under Level 1 or Category 1 in this dissertation comprised cancer types with P16(CDKN2A) and PRSS1 mutations. The cancer types that were included as part of this category were pancreatic, melanoma, esophageal, leukemia, lung, bladder, renal, brain, osteosarcoma (bone), and cancer of the head and neck. Level two or category two includes cancer types with BRCA1, STK11, and LKB1 mutations. While p16 is related to breast cancer, BRCA1 is two times to have a relative risk of PC, with higher risk by age 70. The cancer types that are considered to be part of this category are breast, ovarian, and prostate cancer. Level three or category three are composed of cancer types with bMLH1, and bMSH2 mutations. The cancer types in this category are endometrial, colorectal, and stomach cancer. Regression methods were used to assess and adjust for confounding, and determine whether there is effect modification, as well as simultaneously evaluate the relationships of risk factors (smoking, age, gender). Given that this study involves PC/CTSG-A, and more than one independent variables, ordinal logistic regression analysis was performed to assess confounding and effect modification. The impact of multiple risk factors (smoking, gender, age) is examined as opposed to focusing on a single risk factor. Two separate logistic regression analyses were conducted to assess differences in induction and promotion of pancreatic cancer/CTSG-A by gender and three age groups (<51, 52-69, 70>).

Research Findings

The effect of tobacco use, age, and sex in the etiopathogenesis of PC and CTSG-A was assessed using cumulative odds ordinal logistic regression with proportional odds. While the results of this study supported the null hypotheses that smoking does not correlate with the prevalence of PC and CTSG-A as confirmed by the GENLIN parameter estimates, both gender and age are statistically significant predictors with <.05 p-values. The odds of male respondents developing PC and CTSG-A versus the female respondents is .418 (95% Cl, .344 to .509) with a statistically significant effect, X2 (1) = 75.507. The odds ratio of 1.374 (95% CI, 1.184 to 1.595), Wald χ2(1) = 17.538 is suggestive to the increased probability of developing the disease as the persons reach the age between 62 and 69 years of age. Separate binomial logistic regression analysis shows age was associated with an increased likelihood of developing the disease. Analogous to the results of the ordinal logistic regression analysis, the odds of the male participants of the 2014 BRFSS survey is 2.472 times greater to develop the disease as opposed to female respondents. The findings of this study could support the importance of behavioral risk factor and their roles in reducing the prevalence of PC and CTSG-A, enhancing the late-stage quality of life.

Ab-initio studies have established that family history of PC can manifest due to genetic factors and shared environmental factors. The scientific perspective of this dissertation, current, and past studies are parallel to Albert Einstein’s concept of “natura naturans”—everything is connected. In this dissertation, the assumption that P16(CDKN2A), PRSS1, BRCA1, STK11, LKB1, bMLH1, and bMSH2 are correlated with the development of the disease is mathematically or statistically correct and deserves further investigation.

Presenting a New Metatheory

The Unified Paradigm of Cancer Causation (UPCC), a metatheory introduced in this dissertation could provide arguments on the positive association (synergism) between tobacco use and FCH, giving more clarity to Rothman’s notion of epidemiologic interaction or the paradigm of sufficient cause. UPCC is a composite construct of the germ theory and the somatic mutation theory of carcinogenesis (SMT) in combination with the traditional or Darwinian evolutionary system (Greaves & Maley, 2012), Knudson’s two-hit theory (Hermanowicz, 2015), genome theory, Darwinian theory of social change (Richerson & Boyd, 2000), and the multi-level biologic, social integrative construct (MBASIC). The theoretical cocktail of UPCC could interlock new insights on tumor initiation, metastases diagnostic, and treatment strategies. The dynamic interplay of gene-culture transmission recognized in UPCC could initiate the evolution of culture that embraces the value of evidence-based screening, surveillance, management, and personal genomics. Central to human adaptations is the use of socially learned information (Richerson, Boyd & Henrich, 2010), from literacy program of a health system, emphasizing the significance of 21st-century approach. The combined causal association of a variety of levels as recognized by Lynch and Rebbeck (2013) that are linked to cancer incidence and mortality justify the supposition of UPCC. It is critical to underscore the magnitude of intercalating the mandatory early screening, and management of the health system. The complex, integrative approach of UPCC supports the views of Loomis, and Wing (1990), Pearce (1996), and McEwen and Getz (2013) in embracing the new epidemiologic paradigm congruent to the advances in cancer genome sequencing. Theorizing the pathopoiesis mechanism of smoking, inherited genes, and association of gender and age in the etiopathogenesis of PC/CTSG-A warrants exploration of its causal footprints, conjoining both biomedical and lifestyle (Krieger, 2011).

New Public Health at the Level of Society and Individual Behavior

Darwinism is a collection of concepts, empirical methods and mathematical tools designed to understand the dynamics of genetics and cultural evolution (Richerson & Boyd, 2000). Therefore, this dissertation supports the rationale of cultural value transmission of smoking cessation that could lower the risk to individuals with CPG. Smoking cessation as a cultural item is a clear implication for positive social change. While smoking cessation is the probable social implication of this dissertation, it is important to stress the epidemiologic value of a study on the apparent correlation between gender and age, modification effect of tobacco use among individuals with PC and CTSG-A. The outcome of a risk factor epidemiologic study in individual terms could uplift precision medicine to meet the challenges in tailoring medical interventions based on patient’s biological profile, genetic and epigenetic traits, giving a better understanding of EGBIs. The results of this dissertation have several implications for social change, such as recognizing cultural values in developing effective communication structured from the statistically significant etiopathogenic role of gender and age in the development of PC and CTSG-A. This will give a clear understanding of what to ask, and what actions to take, allowing the family to openly explore treatment alternatives during the terminal phase of the illness (Ballard-Reisch & Letner, 2003). Primary prevention must be prioritized as an integral part of global cancer control. No regulatory standards nor advanced innovations could change the hearts and minds of the general population unless evidence-based studies support it. Social change will be dependent upon the continued dissemination of current cancer research built on integrative social molecular pathological epidemiology (MPE). Pearce (1996) argue that epidemiology must reintegrate itself into public health and must rediscover the population perspective. However, while the new paradigm of downstream (individual) approach could produce a lifestyle approach to social policy, the cumulative outcome of research in cancer epidemiology could equate positive implications to population health.

Improving the future of individuals diagnosed with PC through the concerted efforts of policymakers, public health professionals, clinicians and scientists, the Recalcitrant Cancer Research Act of 2012 lays the foundation for a heightened focused on further development and use of prevention, screening and therapeutic strategy (Rahib et al., 2014). The genuine progress against PC as recalcitrant cancer warrants strategic direction and guidance on the continued understanding, development of efficient early detection strategy and identifying therapeutic targets that could stem the tide of its growing economic burden.

References

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