Pancreatic Cancer: increasing incidence

 A new analysis found that pancreatic cancer incidence seems to be increasing over time (see pancreatic cancer increasing JAMA2021 in dropbox, or doi:10.1001/jama.2021.18859).

 

Details:

-- data from the Surveillance, Epidemiology, and End Results (SEER) database

-- they calculated the annual percentage change and the average annual percentage change (AAPC) based on this data

-- they assessed younger adults (<55yo) versus those older, with a post hoc analysis of those 15-34yo and 35-54yo

 

Results:

-- from 2000-2018: 283,817 cases of pancreatic cancer reported (50% women)

-- AAPCs (average annual percentage change):

    -- women: increased 0.78% (0.68%-0.88%), p<0.001

    -- men: increased 0.90% (0.82%-0.99%), p<0.001

        -- no statistically significant difference between these two groups

--AAPCs by age:

    -- at least 55 years old: 251,360 cases, 51% women

        -- women: increased 0.62% (0.51%-0.74%), p<0.0001

        -- men: increased 0.92% (0.82%-1.01%), p<0.001

            -- this difference was statistically significant, p<0.001

    -- <55 years old: 32,369 cases (11.4 % of cases, 43% women)

        -- women: increased 1.93% (1.57%-2.28%), p<0.001

        -- men: increased 0.77% (0.50%-1.05%), p<0.001

            -- this difference was statistically significant, p<0.001, though unlike the older group, women had at a higher rate than men

        -- 35 to 54 years old (30,831 cases, 10.9%)

            -- women (13,139 cases): 1.56% (1.24%-1.87%), p<0.001

            -- men (70,692 cases): 0.65% (0.38%-0.91%), p<0.001

                -- significant difference, p<0.001

        -- 15 to 34 yo (1538 cases, 0.5%)

            -- women (896 cases): 7.68% (6.21%-9.18%), p<0.001

            -- men (642 cases): 4.20% (2.54%-5.90%), p<0.001

                -- significant difference, p=0.01

 

 

 

Average annual percentage change in men and women by age

 

Commentary:

-- pancreatic cancer is the fourth leading cause of cancer death, with a five-year survival rate of about 10%

-- the overall conclusion in the study above is that cases are increasing on the order of 1% per year, more in men >55yo than women but more in women <55yo than men; also, the relative risks are higher in those 15-34yo, but the absolute numbers are much smaller, so the relative increase does not translate into quite so many cases

-- my own anecdotal/personal experience is that there’ve been a deluge of pancreatic cancer cases amongst patients and friends, so this study was an unwelcomed validation of that

 

-- a review of the known potentially reversible risk factors (not including some genetic ones, which comprise about 10% of cases), see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6780233/ :

-- Smoking: perhaps the most studied and consistent risk factor, many studies with 100 to 500 participants. There is a consistent relationship between current smokers and increased risk of pancreatic cancer, with a population attributable risk for pancreatic cancer deaths in the 11%-32% range and a relative risk of 1.5 to 3. There is also a pretty consistently increased risk with number of cigarettes smoked, and smoking cessation of 10 to 15 years decreases risk back to that of non-smokers.

-- Diet: several but not all studies found that eating more fruits, vegetables, whole grains, nuts, and fish oils, is associated with a lower risk of pancreatic cancer, and that higher intake of saturated fat, especially smoked or processed meats has been found in some studies to increase the risk. And there are suggestive data that there are adverse microbiome changes associated with pancreatic cancer, though diet, exercise, smoking, etc all affect the microbiome, so the microbiome changes may be from the risk factors instead of being directly related to the cancer

-- obesity/physical inactivity: found in several studies including the Health Professionals Follow-up Study and the Nurses’ Health Study that BMI > 30 versus BMI <23, is associated with an increased pancreatic cancer incidence, relative risk of about 1.7, and an inverse relation with moderate activity, relative risk of 0.45 but specifically in people with a BMI of at least 25

    -- so, in terms of diet and exercise, there may be protection from pancreatic cancer from dietary flavonoids, omega-3, D, fruits, veges, physical exercise: see https://pubmed.ncbi.nlm.nih.gov/27538405/

-- coffee and alcohol consumption: studies on alcohol are quite mixed, with possibly a small association in heavy drinkers; coffee seems to lower the incidence of pancreatic cancer in many studies

-- H. pylori infection: several studies have found up to a two-fold increased risk with H Pylori infection

-- Environment: there was a report finding about 10 million new chemical compounds produced per year, translating to 1100 new ones synthesized every hour and 19 per minute, with very little oversight or analysis of the possible ecological/oncological impacts (see https://www.seeker.com/chemical-pollution-is-soaring-faster-than-we-can-measure-it-2231114982.html and https://esajournals.onlinelibrary.wiley.com/doi/abs/10.1002/fee.1450 ). though the numbers of new chemicals vary drastically in the literature, some stating 84,000, some stating at least 50 million have been made over time, and mostly in the last few decades. and an industry-related website suggesting 8,707. but there does seem to be consensus that the EPA and government have been woefully inadequate in testing chemicals for safety, perhaps only a handful each year (eg see https://www.pbs.org/newshour/science/it-could-take-centuries-for-epa-to-test-all-the-unregulated-chemicals-under-a-new-landmark-bill ). there is some evidence that an array of occupational exposures may be associated with pancreatic cancer, including Ionizing radiation, nonchlorinated solvents, pesticides, inorganic dust containing crystalline silica, heat stress, rubber chemicals including acrylonitrile, eg see  https://pubmed.ncbi.nlm.nih.gov/8562625/ , and also mercury https://pubmed.ncbi.nlm.nih.gov/33276658/ . a couple of related issues:

    -- many chemicals are now additives to foods, or to their containers. there are several relatively recent concerning findings (again, the very tip of the iceberg): BPA (bisphenol-A) used in can linings is considered a human carcinogen. and the slew of other additives, such as emulsifiers (so the peanut butter, or mayonnaise, or ... do not separate in the jars) which disrupt the mucous membrane of the colon, disrupting its role in preventing rapid absorption of chemicals. and all of those preservatives used to let bread etc last much longer on the store shelves and homes. and, my guess, the more we assess these additives, the more bad stuff we will find

    -- and, tied into this is the potential for these additives to substantially change our poor, little (actually quite big) gut microbiome, affecting its many protective functions (infections, cancer, gut-brain axis....). for many, many prior blogs on the microbiome, see http://gmodestmedblogs.blogspot.com/search?q=microbiome 

 

Limitations:

-- the SEER database collects information from cancer registries covering 37% of the US population. Unfortunately, unlike many other countries, we do not have a more inclusive database. But, in our fragmented system, this is the best we have.

-- This database relies on accurate coding, and has little data about comorbidities, covariates (e.g. all of the risk factors noted above)

-- The number of younger people with pancreatic cancer (less than 55 years old) makes the statistical analysis of relative risk more inflated

-- and, as a major limitation in my enumeration of pancreatic cancer risk factors, these are all associations assessed by observational studies and cannot be considered causal: smoking seems pretty consistently associated, but many smokers may also not get as much exercise, perhaps be more in occupations with higher use of chemicals, may not eat as many veges, may drink more alcohol when smoking, etc, etc. And we do not know definitively  if decreasing the above risk factors decreases the risk of pancreatic cancer (though a pretty good guess that they do....)

 

so, pancreatic cancers are increasing at a rate of about 1%/year. the major known risk factors seem to explain a minority of the increase. my concern is that the huge amount and increasing numbers of chemicals in the environment (increasing annually at a shocking rate, but without much regulation or federal safety-checking) in all aspects of our lives (air, work environment, water, food chain etc) is really likely to play an important role, for pancreatic and perhaps most other cancers. There was an interesting article suggesting that organic foods seem to lower overall cancer risk (not specifically pancreatic cancer, but see http://gmodestmedblogs.blogspot.com/2018/10/cancer-risk-lower-with-organic-foods.html ) which supports the concept that pesticides and other things used frequently in the food chain are probably not so great, but it is hard to disaggregate eating organic foods from other healthy behaviors in those on organic diets.  we also know that levels of toxins overall are particularly high in the inner city (eg related to air pollution, living on bus or highly trafficked routes...) and with less access to the higher cost organic foods and more access to highly processed foods in the local markets....

 

geoff

 

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