Earlier age of onset in 17 cancers
A recent massive study found that there was earlier age
of cancer onset in 17 of 34 the cancer types assessed (see cancer early
onset increasing LancetPubHlth2024 in dropbox, or Lancet Public Health
2024; 9: e583–93)
Details:
-- Data on the incidence of 34 cancer types in 23,654,000
individuals aged 25-84yo from 2000-2020, from the North American Association of
Central Cancer Registries (which included the Surveillance, Epidemiology, and
End Results, SEER, database) that included 94% of the US population, and cancer
mortality 7,348,137 the US National Center for Health Statistics
--they analyzed the incidence of the 34 most
common cancer types diagnosed between ages 25-84
--they also analyzed the mortality of 25
cancers, but excluded Kaposi's sarcoma (low numbers of deaths); and breast,
esophagus, oral cavity and pharynx (database did not include subtype
classification)
-- data were evaluated by 5-year birth cohort intervals
from 1920-1990, adjusted for age and period effects (period effects reflected
systematic changes in cancer ascertainment or the influence of newly introduced
or improved medical interventions), from 2000 to 2020
--the analysis compared these 5-year intervals of birth
cohorts to the 1955 cohort as the reference, since 1955 was the chronologic
middle of the birth cohorts examined
--main outcomes measured: the incidence rate ratios
(IRRs) and the mortality rate ratios (MRRs) of the selected cancers, comparing
each 5-year birth cohort to the 1955 one
Results:
-- incidence of cancers comparing individuals in the 1990
birth cohort to the 1955 one:
-- small intestine cancers:
IRR (incidence rate ratio) 3.56 (2.96-4.27)
-- kidney and renal pelvis: IRR 2.92
(2.50-3.42)
-- pancreas: IRR 2.61 (2.22-3.07)
-- also:
-- comparing the 1990 birth cohort to the
1955 one: liver and intrahepatic bile duct cancer in females: IRR 2.05
(1.23-3.44)
-- comparing the 1985 birth cohort to
the 1955 one: non-HPV oral or pharyngeal cancer in females: IRR 1.26 (1.14-2.61)
-- overall, the deviations in IRRs from linear trends by
birth cohorts was significant for 8 of 11 cancers (p<0.05) and was
non-significant for thyroid, soft tissue including the heart, and female
esophageal adenocarcinoma
--main outcomes measured: the incidence rate
ratios (IRRs) and the mortality rate ratios (MRRs) of the selected cancers,
comparing each 5-year birth cohort to the 1955 one
Results:
-- incidence of cancers comparing individuals in the 1990
birth cohort to the 1955 one:
-- small intestine cancers:
IRR (incidence rate ratio) 3.56 (2.96-4.27)
-- kidney and renal pelvis: IRR 2.92
(2.50-3.42)
-- pancreas: IRR 2.61 (2.22-3.07)
-- also:
-- comparing the 1990 birth cohort to the
1955 one: liver and intrahepatic bile duct cancer in females: IRR 2.05
(1.23-3.44)
-- comparing the 1985 birth cohort to
the 1955 one: non-HPV oral or pharyngeal cancer in females: IRR 1.26
(1.14-2.61)
-- overall, the deviations in IRRs from linear trends by
birth cohorts was significant for 8 of 11 cancers (p<0.05) and was
non-significant for thyroid, soft tissue including the heart, and female
esophageal adenocarcinoma
-- cancer mortality rates, comparing the 1990 to
1955 birth cohorts (data were available for 8 cancers): overall there was more
diversity with mortality rates decreasing for some (myeloma, leukemia),
plateauing for others (small intestine and thyroid), fluctuated for others
(pancreas and kidney and renal pelvis), and increased in female liver and
intrahepatic bile duct cancer, with mortality rate ratio, MRR, of 1.36
(1.09-1.69)
-- age-specific average annual percentage changes (AAPCs)
in incidence and mortality rates from 2000-2019:
-- among adults aged 25-49yo:
-- pancreatic
cancer: 4.34% for age 25-29
-- small
intestine cancer: 4.22% for age 25-29
-- overall:
-- several cancers increased across all age groups,
though more rapidly in the younger birth cohorts: uterine corpus, estrogen
receptor-positive breast, and gallbladder and other biliary cancers
-- several cancers had increased incidence only in the younger age
groups: non-cardia gastric and colorectal cancers
-- younger males had very large increases in anal cancer, but a smaller
but still significant increase in testicular cancer
-- some cancers decreased in the younger age groups: ovarian
cancer, uterine corpus cancer in women, testicular and anal cancers in men
I will include the many graphs from the study,
since they provide the visuals of what is happening along with lots of
numbers:
Commentary:
-- a prior study by these researchers reported that cancer incidence rates
progressively increased in successive birth cohorts for 8 cancers: 6 of these 8
are obesity-related
-- recent analysis from 13 US registries found higher
rates in thyroid, colorectal, kidney, uterine corps, and leukemia (mostly about
a 2-fold risk) in individuals in "Generation X" (born from
1965-1980): see cancer inc generation JAMA2024 in dropbox, or
doi:10.1001/jamanetworkopen.2024.15731)
-- for a recent blog on early onset colorectal cancer,
with comments on early onset breast cancer, including thoughts about exposures
that might be playing a role (eg, increasing obesity/diabetes, changes in
important lifestyle issues such as diet and exercise, chronic inflammation
associated with an array of medical/psych issues, exposure to environmental
carcinogens, exposure to microplastics, etc): see https://gmodestmedblogs.blogspot.com/2024/04/colon-cancers-earlier-onset.html
-- this study found that 17 of the 34 most common
cancers increased in incidence in progressively younger birth cohorts in the
US, after adjusting for age and period effects.
--the IRR was 2-3 times higher in the 1990
birth cohort than the 1955 one for an array of cancers (small intestine, kidney
and renal pelvis, and pancreatic in men and women; liver and intrahepatic bile
duct in women), increased in younger cohorts after a decline in older birth
cohorts (estrogen-receptor positive breast cancer, uterine corpus cancer,
colorectal cancer, non-cardia gastric cancer, gallbladder and other biliary
cancer, ovarian cancer, as well as testicular cancer and anal cancer and Kaposi
sarcoma in men)
-- of note, 10 of the 17 incident cancers
are obesity-related: colorectal, kidney and renal pelvis, gallbladder and other
biliary, uterine corpus, pancreas, gastric cardia, estrogen-receptor-positive
breast, ovary, myeloma, and liver and intrahepatic bile duct
-- and the cancer MRRs increased alongside the IRRs
in younger birth cohorts for liver and intrahepatic bile duct cancer in women,
uterine corpus, gallbladder and other biliary, testicular and colorectal cancer
(though MRRs declined or stabilized for most cancers)
-- the big question is what has changed to lead to these
increases in cancer in younger people? Likely several things:
-- increases in obesity and diabetes (the
most rapid rise in obesity has been in the 2-19yo age group)
-- likely increases in exposures to
pesticides (for a detailed review of pesticides and the fact that
"pesticide use has expanded extensively in the recent years", see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9428564/)
-- increased exposure to
phytoestrogens/phytochemicals including both those naturally occurring in foods
due to nutritional changes and those in the environment (for a detailed review
of this, along with the potential epigenetic transgenerational inheritance in
future generations, see https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3644519/)
-- increased consumption of fast foods
(and less home cooking of likely healthier ones): fast food consumption has
increased 2.15% in the US between 2011 and 2016, and more recently with a 5.75%
increase from the same quarter from 2022 to 2023. And, the percentage of adults
consuming fast foods varies inversely with age: 44.9% in those 20-39, 37.7%
aged 40-59, 24.1% in those >60
-- decreasing exercise: daily physical
activity in the US has gradually declined in the past 30-40 years
--the mediators of some of
these are likely related to increases in chronic systemic inflammation (which
can be related to increased stress, depression, sleep deprivation) as well as a
less healthy microbiome (eg, see https://gmodestmedblogs.blogspot.com/2021/11/colon-carncer-increased-with-antibiotic.html for
the relationship between increased antibiotic use and colon cancer, as well as https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10376920/).
And the microbiome is affected by diet, exercise, microplastic exposure, and
systemic inflammation (for the latter, see review: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7589951/ ).
A healthy diet and exercise improve the health of the microbiome
--other societal changes may also play
a role (eg, decreasing birth rate being associated with breast cancer)
-- there may also be some factors that have decreased the
likelihood of cancers, such as decreased smoking rates, decreased alcohol
consumption, even decreased oral contraceptives from the 1970s to 1990s (an
inverse association between oral contraceptive use and ovarian cancer risk has
been found), and the initiation of HPV vaccination in kids and young adults
--prior blogs on early onset cancers:
-- https://gmodestmedblogs.blogspot.com/2024/04/colon-cancers-earlier-onset.html reviews
the data on early onset colon cancer in detail with comments on early onset
breast cancer
-- https://gmodestmedblogs.blogspot.com/search?q=early+onset+breast&updated-max=2024-04-15T05:09:00-07:00&max-results=20&start=1&by-date=false reviews
the new USPSTF recommendations decreasing the age of screening mammograms as
well as commentary on likely reasons for its earlier onset
Limitations
-- there was a discordance between IRRs and MRRs, likely
related to earlier detection and improved therapies for incident cancers (for
example, better mammography, more testing for prostate and lung cancer, etc),
leading to decreased mortality. Still not fun to get cancer even if it is
more treatable now....
--we have no information about the cancer
detection method or the stage of cancers detected in the above study (though
they did control for period effects that reflected systematic changes in cancer
ascertainment or the influence of newly introduced or improved medical
interventions, but it is unclear what this really means)
-- there is no information about the specifics of
individuals developing the cancers: of the 10 noted to be
"obesity-related", did they occur in those individuals who actually
had obesity?
-- as with pretty much all studies, health disparities
and social conditions play a huge role in cancer development, related to
differential access to health care, different social environments that might
lead to more or less cancer, different levels of stress and the associated
chronic systemic inflammation, etc
-- and, over such a long time period
as in this study, there are also lots of moving targets over time making it
hard to pin down a clear reason for the increase in cancers in younger people:
unmeasured changes in income inequality/SES, living situations, stress, types
of exercise and specifics of diet, smoking and alcohol consumption, other
substance use disorders, occupational exposures, environmental exposures,
infections (eg hepatitis C, HIV), etc
-- there may well be misclassification of the cancers
reported: how accurate is reporting of HPV-positive vs negative relevant
cancers?
-- there are likely inaccuracies in mortality from death
certificates: a person with cancer who dies may well have their unwitnessed
death attributed incorrectly to their cancer
so,
-- this current trend to earlier onset cancers is quite
troubling and should really lead to strong public health initiatives for cancer
prevention
-- and, the goal should primarily be cancer
prevention, which is better than just earlier detection as per the guidelines
recommending mammograms or colorectal cancer screening at a younger age
-- which all means that there really should be a
concerted effort to deal with very difficult issues:
-- developing a systematic approach to
improving diet and exercise, including access to healthy foods, decreasing the
inner city and rural food deserts, improving access to exercise venues
including safer streets/neighborhoods for people to get outside for walks etc
-- specifically targeting
obesity (and therefore diabetes) prevention
-- perhaps developing support
groups in the community to inspire and teach cooking skills to decrease the
consumption of fast foods
-- more regulation and enforcement around
toxic chemicals that get into the atmosphere and into our food chain
-- continued reinforcement to decrease
smoking, alcohol, and other substance use
-- aggressive campaigns to decrease
unnecessary use of antibiotics in people and animals in order to help protect
the microbiome
-- specific outreach to millennials and
generation Xers, groups with the most profound changes in earlier onset cancers
-- these
groups are less easy to reach through traditional public health messaging: they
tend to be more connected to social media, which may be an important way to
reach out to them
geoff
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