There are many reasons why a human cell can go berserk and start to multiply uncontrollably until it produces a malignant tumor. Smoking, for example, causes mutations that can lead a cell to reproduce without restraint. Alcohol, excessive exposure to the sun or even chance can also favor these errors in cell replication. However, the most important variable has always been age: the older one becomes, the greater the risk of these errors taking place, because cells degrade, control mechanisms diminish and the defense system deteriorates. However, something has been changing in the traditional expansion of the disease: while age continues to be a determining factor, the cases among young adults are increasing, and the causes are unclear.
A study recently published in the journal BMJ Oncology estimates that the global incidence of tumors among people under 50 years of age has increased by 79% in three decades. Although the data must be viewed with caution due to the differences between regions (the more developed the country, the higher the incidence of early-onset cancer), the use of different sources of information and the probability of under-reporting in developing countries, experts point to unhealthy habits, poor diet, sedentary lifestyles, pollution, excessive consumption of antibiotics and reproductive factors, among others, as responsible for the increase in early-onset cancer. They also do not rule out the possibility that other, still unknown factors might be prompting this change.
The researchers consulted for this story also mentioned the influence of improvements in early detection and the refinement of diagnostic techniques. César Rodríguez, president of the Spanish Society of Medical Oncology (SEOM), explained in an interview with EL PAÍS that these phenomena always have more that a single cause and, in addition to the impact of the Western lifestyle, “detection at a younger age is also sometimes linked to better diagnostic techniques.” A current digital mammogram, for example, is more precise than those done 30 years ago, the oncologist continues. “The more you refine your diagnostic methods and the ability to perform studies that find a tumor, the sooner you will probably diagnose.”
Andrea Wizner was barely 30 years old when she was diagnosed with a breast tumor. At the beginning of 2020, she noticed “a little lump the size of a chickpea” in her breast, and she told her doctors. She was nervous and fearful, but they reassured her: at her age, it was unlikely to be a tumor. Surely it was nothing but a lump of fat. However, the look on her oncologist’s face when she was given the results of her tests destroyed any wishful thinking she might have had: “That chickpea went on to become an infiltrating ductal carcinoma. That’s when the long-distance race began,” says Wizner, who is now 34.
Wizner wondered why. Why her. “I hadn’t had any previous symptoms, nor had I ever set foot in a hospital in my entire life. I am an athlete. I live on an island [Ibiza] with fresh air… I wondered how it was possible.” She felt fear and uncertainty. Facing a cancer diagnosis at that age is not easy, she admits today. “If you have it at that age, you end up thinking that you must have done something wrong. But I knew that I had done nothing to cause it,” she reflects.
The scientific community is still trying to understand this phenomenon, from its scale to its causes. It is not always possible to establish a direct causality when it comes to cancer, or even what factors may be involved; still, there are some points that experts are already clear about, such as that lifestyle plays a determining role. “Changes in diet, lifestyle and environment since the turn of the 20th century, resulting in increased rates of obesity, physical inactivity, westernized diets and environmental pollution, may have affected the incidence of early-onset cancer. Additionally, alcohol, smoking and detrimental pregnancy exposures may have also [played a role],” the researchers state in the BMJ Oncology article.
All the usual suspects, such as smoking or an unhealthy diet (which are also behind other cardiovascular or metabolic diseases) have been increasing in recent decades and may be taking their toll, the experts suspect. Ana Fernández Montes, who is a member of the Board of Directors of the SEOM and an oncologist at the Ourense University Hospital Complex, also advises paying attention to the exposome. That is, all the environmental exposures — such as diet, lifestyle, microbiome, obesity and environment — with which a person comes into contact throughout their life. “Everything we expose ourselves to will determine the risk,” warns Fernández Montes.
Research published in Nature Reviews Clinical Oncology hypothesizes that, although the reasons for the increase in early-onset cancer are not entirely clear, they are “probably related to changes in risk factor exposures in early life and/or young adulthood from the mid-20th century onwards.” Still, they admit, the “specific effects of individual exposures remain largely unknown.”
Earlier periods and late motherhood
Everything plays a role, for better or for worse. Improvements in early detection, such as screening, may have contributed to this increase in cases, although their influence will surely be limited because most systematic early diagnosis programs are aimed at the older population. One example is breast cancer: although there are screening techniques, in many countries they are only available for women 50 and over. But the BMJ Oncology study warns that the incidence of this early-onset tumor also increased in places where there are no routine screening tests. This suggests, according to the researchers, that, in addition to weight gain and increasingly unhealthy lifestyle habits, a change in reproductive factors may have contributed. Scientists mention, for example, the earlier onset of menstruation, the use of oral contraceptives, the older age at first birth and never breastfeeding.
All of these factors contribute to increasing the risk of cancer. Each variable can add points to the individual risk, although initially it is low, says Xavier Castells, head of Epidemiology and Evaluation at the Hospital del Mar in Barcelona. “When we look at the five-year risk, the most important factor is still age. The average risk of having breast cancer in Europe is 1.3%. A high risk would be 2% or 5%. These are the dimensions that we’re talking about,” explains the doctor, who belongs to the team of experts that draws up the recommendations for breast cancer screening in the EU.
Wizner had to undergo six cycles of chemotherapy, one operation and several sessions of radiotherapy to get rid of the tumor. During the treatment she met women like herself; some were even younger. “There was a 24-year-old. No one is safe today,” she reflects now. The BMJ Oncology study estimates that, in this decade, the incidence of early-onset cancer will increase by approximately 31%, especially among people in the 40-to-49 age bracket.
At the doctor’s office, the overall feeling is the same. “We all feel that we are seeing increasingly younger people. Before, the typical patients with colon cancer that I saw used to be people over 65 years of age; it was very rare to see a 48-year-old patient. Now I have patients aged 36, 40 or 43. Those cases used to be rare,” says Ana Fernández Montes.
Regarding colorectal cancer, a study published in the journal Science points out that this type of early-onset tumor is “increasing globally and anticipated to become the leading cause of cancer death in individuals aged 20 to 49 in the U.S. by 2030.″ The authors admit that the exact reasons remain unknown.
Colorectal cancer has always been associated with aging, which is why screening with a fecal occult blood test is usually done after the age of 50. However, risk factors such as obesity, diabetes or a sedentary lifestyle are also traditionally linked to this disease. Elena Elez, an oncologist at Barcelona’s Vall d’Hebron Hospital and main researcher of the Vall d’Hebron Institute of Oncology (VHIO) colorectal cancer group, points out that 25% of colorectal cancer “has a hereditary component” and, in patients under 40 years of age, that was usually the case: “They had a family history.” But not anymore, warns the scientist, who also highlights the role of all human exposures, even from the prenatal stage.
The role of the microbiome
The experts are looking closely at the microbiome, which is the entire ecosystem of microbes that populate the intestine and take part in key functions of the body such as the defense against foreign agents. No two microbiomes are the same. Everything varies depending on exposure to certain circumstances; for example, if a baby is born by cesarean section or natural birth, the type of diet or the consumption of antibiotics. “Humans are the invading organism of bacteria. The microbiome is modulated with antibiotics, for instance, and these drugs are being more used now and could be having an effect,” explains Fernández Montes.
Elez is part of an international project to study the role of the microbiome, learn if it is a risk factor and, if that is the case, how to modulate it: “There is a type of bacterium, Fusobacterium nucleatum, which is seen most frequently in a type of colorectal cancer. The existence of this bacterium in the tumor and in liver metastases has been shown,” explains the oncologist from Vall d’Hebron. It is not known whether this bacterium or others are transient or if they cause the disease, but the scientific community continues to investigate their potential in the genesis or prognosis of cancer. “Certain bacteria make immunotherapy treatment more effective or have fewer side effects,” emphasizes Elez.
Although the average individual risk is low, both for breast cancer as well as other tumors, the rise of early-onset neoplasms has opened the debate on whether or not it is appropriate to start the screenings earlier or refine these early detection tests to higher risk profiles. The EU advisory group of which Castells is part, for example, has recommended extending the age for breast cancer screening both upwards and downwards: “For women with medium risk, it is being proposed to bring it to 45 and continue until 74, which would increase the target population by 50%. We lowered the age because we believe there have already been enough studies showing a mortality benefit that outweighs the risks [such as false positives or overdiagnosis]. From 40 to 45 it is recommended not to do it, but we are conducting studies to see if it makes sense to start earlier in a subgroup of women,” explains Castells, alluding to women with high breast density (with this type of breast, potential lesions are not well seen on a mammogram), a family history of breast cancer, a personal history of benign lesions or a genetic predisposition.
The scientists admit that there are still many gaps in the research. In fact, Harvard researchers point out that this early-onset cancer “epidemic” might actually be part of something bigger; it could be “just one manifestation (the tip of the iceberg) or an example of an increasing trend towards greater incidences of many chronic diseases in young and/or future generations.”
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