Revealing the more subtle risk factors for early-onset cancers
Written By Charvi Varampati
Introduction
Waiting times are decreasing but are yet to completely recover from the COVID-19 backlog. A rise in various environmental risk factors, an increasing frequency of chronic infections and inflammation, driven by emerging strains of bacteria and viruses; together, these are creating a perfect storm for early-onset cancers to develop and potentially progress further.
According to Cancer Research UK, there has been a 24% rise in the incidence of cancers diagnosed in the 25-49 age group from 1995 to 2024. This highlights a pressing need for addressing earlier-onset cancers as they can have immense physical, social and psychological effects on the individual patient and their family.
Improvements in diagnostics and better access to screening campaigns may have contributed to higher numbers of diagnoses in the younger generation. However, these are unlikely to be the only cause of the rise in early-onset cancer diagnoses. So, what is driving this earlier development of cancers?
Many risk factors may have contributed to the increase in earlier-onset cancers such as air pollution, microplastics and carcinogens (such as those found in tobacco).
Although rates of cancer in young individuals have increased overall, this article will focus on three types of cancer showing the steepest rise: colorectal cancer, breast cancer and gynaecological cancers including cancer of the endometrial lining, ovaries, cervix and vagina).
Role of metabolism
There is widespread knowledge among the general public about the adverse impacts of consuming food with refined sugars and trans fats. What does current research show about how this might relate to cancer?
Research has suggested that ultra-processed foods present in Western diets can disrupt the gut microbiome, impairing the immune response. Carcinogens can increase the number of pro-inflammatory bacteria and can lead to increased permeability of the intestinal membrane, allowing more toxins to enter. Combined with a lack of protective nutrients from fruit and vegetables, mutated cells take advantage of these factors to proliferate rapidly. Therefore, unhealthy diets can predispose younger people to colorectal cancer.
Perhaps less commonly addressed is the impact of metabolism on breast cancer and gynaecological cancers. Metabolic imbalances, particularly those present in obesity and type 2 diabetes, can contribute to increased oestrogen levels. Since oestrogen stimulates the growth of breast tissue and female reproductive tissue, this link is very important to consider. I was informed by a gynae-oncology surgeon that oestrogen levels are released at higher levels by fatty tissue. Therefore, obesity is a major risk factor for cancers in oestrogen-sensitive tissues. Furthermore, the insulin resistance associated with type 2 diabetes also increases production of oestrogen, leading to similar effects.
Infections and inflammation
Another key factor linked to early-onset cancers is the role of infection and inflammation. Following the COVID-19 pandemic, there has been a much greater focus on how infections interact with other health conditions. Persistent infections can lead to chronic inflammation and are linked to immune dysregulation, which is a hallmark of cancer. How can inflammation drive cancer development and progression?
While infections seem to exacerbate cancers, there haven’t been many direct links between a specific infection and cancer development. Further research is being carried out, to investigate this further. The only infection that seems to directly cause cancer is human papillomavirus (HPV), the primary cause of cervical cancer. An effective vaccine is currently available for all children aged 12 to 13.
Rather than the infections themselves, the resulting inflammation seems to be driving cancer development. Bacterial and viral infections can activate inflammatory signalling pathways, stimulating the conversion of proto-oncogenes into oncogenes. Proto-oncogenes are involved in the normal regulation of cell differentiation and growth. Oncogenes are mutated versions of proto-oncogenes which promote dysregulated proliferation.
Surprisingly, inflammation can also be closely linked to diet and metabolism. The dietary inflammatory index (DII) is a scoring system that measures the effect of various foods on inflammatory biomarkers. A paper published in 2018 conducted a systematic review to assess the association between the dietary inflammatory index and gynaecological cancers. The results showed that women who consumed higher-DII diets had an increased risk of early-onset gynaecological cancers, echoing the previous section on metabolism. Pro-inflammatory diets are more likely to lead to oxidative stress, increasing the risk of DNA damage. This happens because reactive oxygen species (oxygen radicals) attack components of DNA inside the cell. These oxygen radicals can oxidise DNA bases and break the strands of DNA, leading to mutations.
Why is considering these risk factors important?
After discussing the role of metabolism and inflammation in promoting the rise in early-onset cancer, it is crucial to understand how these exposures can escalate over time. A 2024 study in the Annals of Oncology highlights that earlier exposures should be considered as they generally have a longer latency. This suggests that exposure to carcinogens from a young age can have a large impact on an individual’s risk of cancer between the ages 25-49. Therefore, it is important to educate the public about these risk factors from a younger age.
What support is available for young people with cancer?
It is vital to ensure that younger patients facing the difficult diagnosis of cancer receive the support they require. There are many charities whose objective is to create a welcoming atmosphere for patients. Maggie’s provides expert medical and psychological support for patients of all ages. Young Lives vs Cancer is a charity that specifically caters to younger cancer patients and provides support via text, email and a helpline.
Being prepared for potentially having difficult conversations is particularly important for young patients with gynaecological cancers. Many young women may value having children but their fertility may be impacted by gynaecological cancers or treatments (such as some surgeries and chemotherapy). The Eve Appeal is a charity that can help to support these patients. Alongside this, the charity also raises awareness about screening programmes.
As well as charities, there are also specific campaigns that aim to raise awareness about early-onset cancer. For example, ‘Be Clear On Cancer’ is a program, led by NHS England, to encourage individuals to approach their GP if they experience any signs or symptoms related to cancer. For colorectal cancer, Bowel Cancer UK’s ‘Never Too Young’ campaign focuses on educating the younger generation about the risks and causes.
As medical students, recognising the impacts of early-onset cancers and knowing how to support patients faced with this difficult diagnosis is vital for improving our practice as future doctors, and for our own health as young people.
Read the rest of the edition here