G. M. Jacquez

Our Dear Friend and Colleague Jawaid Rasul 8/2/ /22/2011

Research stage In progress Monograph completed arcinogenesisandcancerstagespancreaticcancer.pdf arcinogenesisandcancerstagespancreaticcancer.pdf Not yet peer-reviewed

Abstract: Pancreatic cancer has been called the "silent killer" because it is typically diagnosed at advanced stages and because the prognosis is so poor, with a mean survivorship of about one year. The last five years have seen an increased understanding of the genetic basis of pancreatic cancer, and the cascade of mutations and pathways that lead to carcinogenesis are beginning to be elucidated. However, these have yet to be incorporated into models that bridge scales from the cellular to the individual, to the population. We present two compartmental models of pancreatic cancer. The first models pathways and events at the molecular and cellular level that lead to pancreatic cancer, the second deals with cancer stage at diagnosis and may be estimated using cancer registry data. Residence times in these models corresponds to cancer latency, which has implications for cancer surveillance and medical geography.

Problem Approach Results Conclusion

Problem Approach Results Conclusion

Genome + Exposome Behavsome

The Challenge How to integrate burgeoning knowledge of genomics, environment and behaviors to forecast cancer outcomes, and to improve cancer surveillance and control?

Solution characteristics Estimates disease latency Bridges biological scales Genetic – molecular – organ – individual – population Generalizable Across cancers and populations Useful Models can be employed with currently available data based on reasonable assumptions; predict silent cancer burden; conditions for cancer metastasis and remission

Problem Approach Results Conclusion

Compartmental analysis

Residence times in compartmental systems

Model coefficients & parameters

Linking carcinogenesis and stage

Pancreatic cancer in SE MI 11,068 incident cases , SE Michigan 8,826 cases with known place of residence and known stage at diagnosis. Males accounted for 4,202 cases and females 4,424. 6,356 cases were whites, 2,192 blacks, and the balance American Indian (8 cases), Asian (61) and other or unknown groups (9).

Problem Approach Results Conclusion

Latency estimates Closed form solution, disease latency ~Erlang ~21.2 years initiation to diagnosis

Conditions for remission and metastasis

Silent cancer burden

Problem Approach Results Conclusion

Conclusions Provides estimates of disease latency using the Erlang distribution Bridges biological scales Genetic – molecular – organ – individual – population Appears generalizable Across cancers and populations Appears useful Models can be employed with currently available data based on reasonable assumptions; predicts silent cancer burden; conditions for cancer metastasis and remission

Caveats Not yet peer-reviewed! Check it out cinogenesisandcancerstagespancreaticcancer.pdf