The unknowns surrounding the mysterious rise of cancer in young adults

The increase in cancer among young adults has oncologists on edge. So much so that the European Society for Medical Oncology (ESMO) congress, held recently in Barcelona, gave a talk on the subject to a packed room. Hundreds of oncologists from all over the world attended a lecture delivered by Shuji Ogino, a professor of Epidemiology at Harvard Medical School, on this “emerging global epidemic” that has specialists deeply concerned.

According to a study published in the journal BMJ Oncology, tumors in people under the age of 50 have increased by almost 80% in the past 30 years, but scientists have not yet managed to fully get to the bottom of why. The experts consulted say that current lifestyle habits are playing a significant role but may not explain the whole story. Moreover, according to Ogino, the increase in early-onset cancer is only “the tip of the iceberg” regarding a global rise in chronic diseases over several generations.

“We are seeing an increase of cases in young patients, and we are concerned because it is not always related to a specific cause,” says Ángela Lamarca, an oncologist at the Fundación Jiménez Díaz hospital in Madrid and spokesperson for the ESMO congress. This emerging tendency mostly concerns colorectal cancer, but it also occurs in other areas, such as pancreatic, esophageal, kidney, liver, biliary tract, gallbladder, stomach, head and neck or breast cancer, among others.

“Several studies have been done to analyze whether there is a molecular cause that explains why there are more cases in young patients and, many times, we have been surprised to find that, at the molecular level, young patients have tumors that are very similar to those that occur in older patients. We still need to investigate and understand better if there is something at the molecular level that we have not been able to identify or if it is entirely related to risk factors,” says Lamarca.

The origin of early onset cancer is not clear. There are probably many different contributing factors. Researchers believe that, although more and better detection of certain tumors may be playing a role, this would not explain the overall increase in cases, as some do not have early detection tests and most screening is performed after the age of 50, not before. Family history and hereditary syndromes, on the other hand, may account for a portion of new diagnoses, but these are not among the most frequent. Most cases are sporadic with no familial or hereditary link and remain unexplained.

Lamarca gives the example of pancreatic cancer. Oncologists are seeing cases of pancreatic cancer at 40, when it was previously being detected in people over 65. “We thought that young patients might develop pancreatic cancer because of something that was putting them at greater risk, but we have not always found what that is. It is true that there are hereditary syndromes, such as BRCA [people with mutations in these genes], also associated with breast and ovarian cancer that can explain pancreatic cancer in a young person, but this does not account for all the young patients we find. So, why do these young patients develop pancreatic cancer which is the same as what we see in a 65-year-old when analyzed at a genetic level? We don’t know,” says Lamarca.

What is clear to the scientific community is that unhealthy lifestyle habits play a fundamental role. Western diets, rich in carbohydrates and processed food that lead to obesity clearly contribute, as does a sedentary lifestyle, and toxic habits such as smoking and alcohol, explains David Páez, an oncologist specializing in digestive tumors at the Hospital Sant Pau in Barcelona. “The risk factors are the same as for cancer in older adults, but it is not known whether there is something else influencing the early onset of cancer,” Páez says.

The BMJ Oncology study concludes that “dietary risk factors, alcohol consumption, and tobacco use were the main risk factors for major early-onset cancers.” But it adds that “prospective lifetime cohort studies are needed to explore the etiologies [causes] of early-onset cancers.”

Risk exposures since childhood

What matters is not only current behavior, but also past behavior and the environment in which a person has grown up. And even before birth. Páez points to the key role of the ‘exposome,’ which are all those non-genetic factors to which an individual is exposed throughout their life and which condition their health. “The interaction of these external factors with the genome can influence the appearance of diseases. It is thought that these factors may be altering the immunity of individuals or the composition of the microbiome from the prenatal period.”

Similarly, a group of Harvard researchers, including Ogino, point out that the first phase of carcinogenesis could start very early: “In utero exposures can lead to cellular reprogramming, including epigenetic alterations, which could have long-lasting effects on susceptibility to chronic diseases,” they note. In fact, they suspect that reproductive factors, such as the age of a woman’s first period, breastfeeding, fertility rate, use of oral contraceptives, as well as smoking, diet, alcohol consumption, lifestyle and previous diseases of the mother during pregnancy “could be relevant intrauterine exposures.”

Exposure to long-term risk factors begins early in life. What we see now is the result of decades of exposure

Shuji Ogino, Professor of Epidemiology, Harvard Medical School

In this regard, during the ESMO presentation, Ogino stressed that early-onset cancer is probably influenced by both nature and nurture. “Exposure to long-term risk factors begins early in life,” he says. “What we see now is the result of decades of exposure.” What is also unclear to scientists is the weight of each risk factor at any given time in life and how each factor interacts with others.

Precisely because of the long latency period of cancer and the change in exposure to various environmental and lifestyle factors, experts stress the importance of the birth cohort effect in colon cancer. This means that each generation experiences a higher risk of early-onset cancer than the previous one. In a podcast in the journal Science, Kimmie Ng, a researcher at Dana-Farber Cancer Institute in Boston who has studied the rise of colorectal cancer in young adults, explained that “it’s something that is affecting generation after generation, with people born in 1990 having a significantly higher rate of developing colorectal cancer compared to people born in 1950.”

Kimmie Ng added, “We think it’s due to environmental exposure. To what exactly? We don’t know. Again, we’ve looked at obesity, we’ve also looked at sedentary behavior, higher consumption of sugar, sweets and drinks, lower levels of vitamin D, and they all seem to be associated with increased risk, but I don’t think that’s the whole story.”

Later diagnoses

Scientists are also investigating the specific characteristics of these early-onset tumors. To begin with, these tumors are unpredictable, since there are no early detection tests to anticipate the diagnosis, nor are there screening tests for these age groups. In the consultation room, oncologists point out that the tumors are discovered already in advanced stages: “They are usually detected in symptomatic stages – in the case of colon cancer, for example, when there is bleeding in the stool, abdominal pain or changes in bowel habits. What is seen is a diagnostic delay with respect to older adults and in young people it takes about six months longer to diagnose,” explains Páez.

Some research also warns that these are more aggressive tumors, but it is not clear whether this is due to the biology of the cancer itself, which is more virulent, or to the fact that it is diagnosed in advanced stages. “In colon, it is not clear whether there are molecular differences between tumors in older and younger adults,” says Páez. “The worse prognosis is attributed more to the delay in diagnosis.” An article by researchers at the University Hospital of Navarra, who have designed a study to analyze early-onset cancer in northern Spain, broadens the focus and states that early-onset gastrointestinal tumors “present in advanced clinical stages and with aggressive phenotypes.”

These patients pose new challenges for specialists. The treatment is the same as if they were older adults, but the consequences of this diagnosis differ in the young population, warns Páez: “It is a challenge from the point of view of the possible sequelae resulting from the type of treatment or surgery and their impact on quality of life. And then, the long-term risk of developing another cancer is also greater.” Páez also points to more psychosocial problems, including stigma, mental health issues and the impact on working life as well as on reproductive and sexuality-related issues.

For the time being, the tools to tackle this phenomenon are limited. “Dissemination and awareness” of the situation, avoidance of risk factors and further research is needed to see if it makes sense to lower the age of screening, says Páez. In the U.S., this has been done, but it is still under discussion among scientists. It is also necessary to find tools for early detection.

Pedro Pérez Segura, member of the Standing Committee of the ECO Foundation and head of Medical Oncology at the Hospital Clínico San Carlos in Madrid, also advocates “educating” people about lifestyle: “We are witnessing a new boom in tobacco and alcohol consumption among the younger population. And we are living in an era in which sedentary lifestyles are common. We must reinforce health education to avoid all this and also remember the importance of sun protection because the incidence of skin lesions is also growing.” In the UK, specialists have specifically flagged up the risks of processed foods, which includes ready-made meals and pizzas, which young people tend to consume more of.

Lamarca also insists on the importance of seeing a doctor when symptoms, however minor, are noticed: “If people have symptoms, they should go to the doctor,” she says. “Many times, a young patient may have symptoms, such as weight loss, abdominal pain or other nonspecific things, and they do not give these any importance because they figure: ‘How can it be cancer if I am 40 years old?’ Well, the reality is that there are more and more cases of cancer diagnosed in the younger population and many times they are diagnosed later, precisely because they do not go to the doctor, because they minimize the importance of the symptoms.”

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