July 28, 2021
Random Chronic Stress Is a Major Cause of
Pancreatic Cancer
28 July 2021
Pancreatic cancer is a major cause of US cancer death. It has risk factors that are
preventable, such as cigarette smoking, excess weight, type 2 diabetes, excessive alcohol
use and diabetes (Pernick, How Pancreatic Cancer Arises Based on Complexity Theory,
2021). It also has risk factors that are not, such as having blood groups A, B or AB (i.e. not
O). This abstract discusses random chronic stress or bad luck, another major cause of
pancreatic cancer that is not preventable (Curing Cancer Blog – Part 7 – Random Chronic
Stress), which is also a major cause of lung cancer in nonsmokers (Pernick, How Lung
Cancer Arises, Based on Complexity Theory, 2021).
This subject was discussed in the abstract below, which was not accepted at a recent
conference. Although disappointing, the advantage of this rejection is that I can publish it
without any restrictions. The full paper is at
http://www.natpernick.com/PancreaticcancerFeb2021.html. I welcome your comments to
Random Chronic Stress Is a Major Cause of Pancreatic Cancer
Pancreatic cancer is the third leading cause of US cancer death, projected to become #2 by
2030. Patients have a 5 year relative survival rate of only 10%. Unlike other cancers, there
have been minimal improvements since the mid-1970s. Many cases have no apparent risk
We analyzed the population attributable fraction (PAF) of known risk factors and estimated
the proportion due to random chronic stress / bad luck. We then analyzed possible
mechanisms for the initiation of pancreatic malignancy.
Random chronic stress accounts for 25-35% of US cases, calculated as 100% minus the
PAF of known risk factors. It causes an estimated 2 cases per 100,000 people per year (age
standardized), accounting for 13,360 age adjusted cases.
We define random chronic stress as seemingly random cellular “accidents” that cause
network dysfunction, promoted by prolonged lifespans, that may propagate to surrounding
networks and promote malignancy, including (a) DNA or related replication errors in
noncancerous stem cells; (b) errors in how DNA is organized or modified by epigenetic
events; (c) errors in the distribution of cell components during cell division; (d) failure to
restore physical interactions between tissue components after cell division, such as contact
inhibition and (e) immune system dysfunction that, for a particular patient, is ineffective at
eliminating premalignant or malignant cells. The category of random chronic stress / bad luck
may include cancer risk factors not yet discovered, too infrequent to achieve statistical
significance or not clinically evident in a patient, such as chronic pancreatitis without
symptoms or microscopic changes.,
Based on self-organized criticality, our cellular networks are poised at a critical state in which
small disturbances rarely set off a cascade of changes in the initial network, with long
periods in which minor changes accumulate with no apparent clinical or microscopic
changes, followed by bursts of activity leading to obvious premalignant or malignant
changes. In evolution, punctuated equilibrium acts similarly. This is in contrast to gradualism,
or stepwise cancer progression, which is logical and predictable but does not accurately
describe malignant progression or evolution.
In lung cancer, patients with no risk factors have superior survival compared to those with
risk factors; for pancreatic cancer, this is true of nonsmokers vs. smokers, but data is
otherwise limited.
Due to these baseline rates of pancreatic and lung cancer, new cancers will continue to arise
and a “world without cancer” is not foreseeable.