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Cancer in younger adults

Cancer is sometimes referred to as a “disease of aging.” For the most part, this is an apt description. People over the age of 65 represent 16% of the population but comprise more than 60% of cancer diagnoses1.

Unfortunately, cancer is not a disease exclusively of aging. About 80,000 young adults (ages 18-39) are diagnosed with cancer each year in the United States, which is about 4% of cancer diagnoses2. Indeed, here at PHM, about 7% of the cancer patients we have managed have been under 40, and nearly 20% have been under 50.

These data converge with a concerning trend. Overall, cancer diagnoses are falling, but cancer incidence among young adults has been increasing year-over-year for decades3.

Why do some people develop cancer at a younger age?

Cancer is considered a disease of aging because cells acquire more mutations as time progresses. As more cells with more mutations accrue, chances are a cancerous cell will emerge4.

A person is predisposed to getting cancer at an earlier age when something has accelerated the process of accumulating mutated cells. This can occur when the rate of mutations increases, or when the immune system does not eliminate enough mutated cells. Inheriting certain genes (aka family history) is one way. If someone inherits a defect in a gene that normally repairs DNA, more mutations occur earlier in life. A well-known example is the BRCA gene. Women who inherit a BRCA mutation are predisposed to certain cancer decades earlier than women who do not5.

Chronic conditions, infections, exposures to toxic substances, and lifestyle are also factors that can influence mutation accrual6, and some of these are trending in the wrong direction for young adults.

Why is cancer incidence in young adults increasing?

Cancer incidence increases for two reasons. 1) Increased surveillance detects cancers at an earlier age. Or, 2) Something has predisposed more individuals to getting cancer at an earlier age2.

Thyroid cancer is the most commonly diagnosed cancer in young adults, and diagnoses have tripled since 19802. Still, mortality has remained steady, suggesting the disparity is due to increased surveillance of the indolent cancer, rather than a real incidence increase7. However, real incidence has increased for cancers such as breast, kidney, uterine, pancreatic, and colorectal cancer3.

Of these, the clearest example is colorectal cancer, where a rise is observed beginning with those born around 19606,8. Likely reasons include an increase in obesity and diabetes9,10, changes in alcohol and red meat consumption11, and a decrease in physical activity12 in the younger population.

As with inherited mutations, these factors increase incidence of cancer because they increase a person’s likelihood of acquiring extra mutations. Diabetes and obesity can lead to chronic inflammation that promotes cell growth and accelerates the mutational process13,14. Alcohol, in addition to inducing inflammation, is metabolized into a compound called acetaldehyde, which directly damages DNA15. Red meat digestion produces chemicals called N-nitroso-compounds, which also directly damage DNA16. Physical activity has the opposite effect. It reduces body fat, lowers insulin levels, and promotes faster digestion time, which lowers inflammation and lessens the time these chemicals have to damage cells lining the colon17.

Is cancer in younger adults different from older adults?

Cancer in young adults is often diagnosed at later stages and is more likely to progress faster. For example, women who are diagnosed with breast cancer before the age of forty often present with more aggressive sub-types, such as triple-negative or basal-like breast cancer18. Colorectal cancer is more likely to be advanced at diagnosis with a poor prognosis19.

It is not clear why early-onset cancers are more aggressive, but it is logical that the same factors that caused earlier onset could also make it more aggressive—namely, more mutations in a shorter time. Supporting this notion, early-onset cancers have a unique biology characterized by differences in mutation and expression patterns20.

Is treatment different for young adults?

With the possibility of additional decades of life ahead, more intense treatment may be warranted and is usually better tolerated. And post treatment, active surveillance is an important consideration. New analysis suggests those who undergo long-term active monitoring live longer than those who do not21,22.

Furthermore, a young person with cancer may wish to have biological children in the future, so specialists in oncofertility are vital members of a care team. They can help determine if a treatment regimen is likely to damage reproductive organs or gametes, can manage fertility preservation options, and can share what risks could come with conceiving in the future23.

What can be done?

If caught early, most cancers are highly curable. So, if a young person is predisposed to cancer due to a genetic mutation or other high-risk conditions, such as diabetes or obesity, surveillance is crucial. For those patients, procedures such as colonoscopies and mammograms should begin much earlier than the recommended 50 years old24,25. In addition, new tests that measure microscopic cancer in the bloodstream could be indicated. These can detect many cancers earlier than imaging techniques26.  Overall, being aware of one’s baseline cancer risk and taking steps to mitigate it as much as possible using lifestyle changes and surveillance is critical for all young people. 

References

  1. Berger, N. A. et al. Cancer in the elderly. Trans Am Clin Climatol Assoc 117, 147-155; discussion 155-146 (2006).
  2. Miller, K. D. et al. Cancer statistics for adolescents and young adults, 2020. CA Cancer J Clin 70, 443-459, doi:10.3322/caac.21637 (2020).
  3. di Martino, E. et al. Incidence trends for twelve cancers in younger adults-a rapid review. Br J Cancer 126, 1374-1386, doi:10.1038/s41416-022-01704-x (2022).
  4. Tomasetti, C., Li, L. & Vogelstein, B. Stem cell divisions, somatic mutations, cancer etiology, and cancer prevention. Science 355, 1330-1334, doi:10.1126/science.aaf9011 (2017).
  5. Okano, M. et al. The relationship between BRCA-associated breast cancer and age factors: an analysis of the Japanese HBOC consortium database. J Hum Genet 66, 307-314, doi:10.1038/s10038-020-00849-y (2021).
  6. Stoffel, E. M. & Murphy, C. C. Epidemiology and Mechanisms of the Increasing Incidence of Colon and Rectal Cancers in Young Adults. Gastroenterology 158, 341-353, doi:10.1053/j.gastro.2019.07.055 (2020).
  7. Davies, L. & Welch, H. G. Current thyroid cancer trends in the United States. JAMA Otolaryngol Head Neck Surg 140, 317-322, doi:10.1001/jamaoto.2014.1 (2014).
  8. Sung, H., Siegel, R. L., Rosenberg, P. S. & Jemal, A. Emerging cancer trends among young adults in the USA: analysis of a population-based cancer registry. Lancet Public Health 4, e137-e147, doi:10.1016/S2468-2667(18)30267-6 (2019).
  9. Liu, P. H. et al. Association of Obesity With Risk of Early-Onset Colorectal Cancer Among Women. JAMA Oncol 5, 37-44, doi:10.1001/jamaoncol.2018.4280 (2019).
  10. Kim, J. Y. et al. Different risk factors for advanced colorectal neoplasm in young adults. World J Gastroenterol 22, 3611-3620, doi:10.3748/wjg.v22.i13.3611 (2016).
  11. Rosato, V. et al. Risk factors for young-onset colorectal cancer. Cancer Causes Control 24, 335-341, doi:10.1007/s10552-012-0119-3 (2013).
  12. Nguyen, L. H. et al. Sedentary Behaviors, TV Viewing Time, and Risk of Young-Onset Colorectal Cancer. JNCI Cancer Spectr 2, pky073, doi:10.1093/jncics/pky073 (2018).
  13. Xu, C. X., Zhu, H. H. & Zhu, Y. M. Diabetes and cancer: Associations, mechanisms, and implications for medical practice. World J Diabetes 5, 372-380, doi:10.4239/wjd.v5.i3.372 (2014).
  14. Hopkins, B. D., Goncalves, M. D. & Cantley, L. C. Obesity and Cancer Mechanisms: Cancer Metabolism. J Clin Oncol 34, 4277-4283, doi:10.1200/JCO.2016.67.9712 (2016).
  15. Johnson, C. H. et al. Molecular Mechanisms of Alcohol-Induced Colorectal Carcinogenesis. Cancers (Basel) 13, doi:10.3390/cancers13174404 (2021).
  16. Gurjao, C. et al. Discovery and Features of an Alkylating Signature in Colorectal Cancer. Cancer Discov 11, 2446-2455, doi:10.1158/2159-8290.CD-20-1656 (2021).
  17. Oruc, Z. & Kaplan, M. A. Effect of exercise on colorectal cancer prevention and treatment. World J Gastrointest Oncol 11, 348-366, doi:10.4251/wjgo.v11.i5.348 (2019).
  18. Murphy, B. L., Day, C. N., Hoskin, T. L., Habermann, E. B. & Boughey, J. C. Adolescents and Young Adults with Breast Cancer have More Aggressive Disease and Treatment Than Patients in Their Forties. Ann Surg Oncol 26, 3920-3930, doi:10.1245/s10434-019-07653-9 (2019).
  19. Willauer, A. N. et al. Clinical and molecular characterization of early-onset colorectal cancer. Cancer 125, 2002-2010, doi:10.1002/cncr.31994 (2019).
  20. Siddig, A. et al. The Unique Biology behind the Early Onset of Breast Cancer. Genes (Basel) 12, doi:10.3390/genes12030372 (2021).
  21. Schumacher, J. R. et al. Surveillance imaging vs symptomatic recurrence detection and survival in stage II-III breast cancer (AFT-01). J Natl Cancer Inst, doi:10.1093/jnci/djac131 (2022).
  22. Tie, J. et al. Circulating Tumor DNA Analysis Guiding Adjuvant Therapy in Stage II Colon Cancer. N Engl J Med 386, 2261-2272, doi:10.1056/NEJMoa2200075 (2022).
  23. Woodruff, T. K. The Oncofertility Consortium–addressing fertility in young people with cancer. Nat Rev Clin Oncol 7, 466-475, doi:10.1038/nrclinonc.2010.81 (2010).
  24. Monticciolo, D. L. et al. Breast Cancer Screening in Women at Higher-Than-Average Risk: Recommendations From the ACR. J Am Coll Radiol 15, 408-414, doi:10.1016/j.jacr.2017.11.034 (2018).
  25. Lieberman, D. A. et al. Guidelines for colonoscopy surveillance after screening and polypectomy: a consensus update by the US Multi-Society Task Force on Colorectal Cancer. Gastroenterology 143, 844-857, doi:10.1053/j.gastro.2012.06.001 (2012).
  26. Liu, M. C. et al. Sensitive and specific multi-cancer detection and localization using methylation signatures in cell-free DNA. Ann Oncol 31, 745-759, doi:10.1016/j.annonc.2020.02.011 (2020).

Authors

Ross Keller

Ross Keller

Research Director

Dr. Keller is focused on providing decision-grade information to cancer patients regarding the best treatments options. He has experience in genomics, cancer evolution, tumor modeling, and early-stage drug development.