title: Heuristic modeling of carcinogenesis for the population with dichotomous susceptibility to cancer: a pancreatic cancer example.
abstract: At present, carcinogenic models imply that all individuals in a population are susceptible to cancer. These models either ignore a fall of the cancer incidence rate at old ages, or use some poorly identifiable parameters for its accounting. In this work, a new heuristic model is proposed. The model assumes that, in a population, only a small fraction (pool) of individuals is susceptible to cancer and decomposes the problem of the carcinogenic modeling on two sequentially solvable problems: (i) determination of the age-specific hazard rate in individuals susceptible to cancer (individual hazard rate) from the observed hazard rate in the population (population hazard rate); and (ii) modelling of the individual hazard rate by a chosen "up" of the theoretical hazard function describing cancer occurrence in individuals in time (age). The model considers carcinogenesis as a failure of individuals susceptible to cancer to resist cancer occurrence in aging and uses, as the theoretical hazard function, the three-parameter Weibull hazard function, often utilized in a failure analysis. The parameters of this function, providing the best fit of the modeled and observed individual hazard rates (determined from the population hazard rates), are the outcomes of the modeling. The model was applied to the pancreatic cancer data. It was shown that, in the populations stratified by gender, race and the geographic area of living, the modeled and observed population hazard rates of pancreatic cancer occurrence have similar turnovers at old ages. The sizes of the pools of individuals susceptible to this cancer: (i) depend on gender, race and the geographic area of living; (ii) proportionally influence the corresponding population hazard rates; and (iii) do not influence the individual hazard rates. The model should be further tested using data on other types of cancer and for the populations stratified by different categorical variables.
authors.affiliation: Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Tengiz
authors.initials: T
authors.lastname: Mdzinarishvili
authors.affiliation: Eppley Institute for Research in Cancer, University of Nebraska Medical Center, Omaha, Nebraska, United States of America.
authors.forename: Simon
authors.initials: S
authors.lastname: Sherman
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D063646:Carcinogenesis / Q000473:pathology*; D004198:Disease Susceptibility; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008297:Male; D008875:Middle Aged; D015233:Models, Statistical; D010190:Pancreatic Neoplasms / Q000453:epidemiology* / Q000209:etiology / Q000473:pathology*; D011379:Prognosis; D012307:Risk Factors; D018426:SEER Program; D014481:United States / Q000453:epidemiology