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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