Author: Helena Bradbury, EMJ, London, UK
Citation: EMJ Oncol. 2024. DOI/10.33590/emjoncol/10304689. https://doi.org/10.33590/emjoncol/10304689.
YOUNG-ONSET COLORECTAL CANCERS
Kimmie Ng, Dana-Farber Cancer Institute, Boston, Massachusetts, USA, opened the presentation by highlighting the incidence rise of young-onset colorectal cancer (CRC). Despite efforts by the United States Preventive Services Task Force (USPSTF) to lower colorectal screening ages, CRC remains the leading cause of cancer deaths among young males, and second among young females.
Throughout her presentation, Ng emphasised the complex interplay between risk factors, and discussed research detailing the association between lifestyle factors, such as obesity and sugar intake, and young-onset CRC. Interestingly, adequate vitamin D intake could be a counter-measure to this, as it minimises the risk for CRC by 50%. Ng went on to explore genetic and epigenetic differences between younger and older-onset CRC, noting the increased TP53 mutation frequency and LINE-1 hypomethylation in younger-onset patients. Commenting on the latter result, Ng stated: “It is also known that LINE-1 hypomethylation may be associated with worse outcomes, and indeed, in the young patients who did harbour LINE-1 hypomethylation, survival was worse.”
The set of unique challenges facing patients with young-onset CRC was a prominent point of discussion. Citing patient focus group and survey results, Ng voiced the mental health and financial concerns experienced by patients following diagnosis, and listed several initiatives launched to directly meet their needs. The Young-Onset Colorectal Cancer Center at Dana-Farber Institute for Cancer, for instance, launched in March 2019, provides multidisciplinary evaluation, cohesive psycho-social support, and personalised treatment. The annual family and patient forum, and quarterly ‘Gut Instincts’ webinar, additionally drive education for both patients and healthcare professionals.
YOUNG-ONSET GASTROINTESTINAL CANCERS
All gastrointestinal tract cancer types have been increasing, most notably appendix, pancreatic, and biliary tract cancers. Ng spoke of the current problems facing patients with non-CRC young-onset cancer, such as limited published information, and smaller patient groups compared to young-onset CRC. According to a 2022 study, established risk factors of pancreatic ductal adenocarcinoma (PDAC), such as smoking, obesity, history of diabetes, tall height, and non-blood O group, have a stronger association with younger-onset than older-onset patients1. Ng emphasised the importance of a healthy lifestyle in early adolescence as a counter factor to this.
With respect to PDAC risk factors, KRAS wild type tumours are prominent in patients with young-onset PDAC. Patients with young-onset PDAC also possess a lower frequency of CDKN2A mutations, and homozygous loss of CDKN2A and SMAD4. Ng explained that more targetable alterations are found within KRAS wild type tumours, giving promising treatment possibilities for patients.
Drawing on oesophagogastric cancer, Ng listed known characteristics of the disease, including higher prevalence in non-White females, and the presence of higher risk histologies such as signet ring cell and diffuse type cancer. Whilst the underlying aetiology remains unknown, subtle genomic differences were again identified between younger and older-onset patients.
FUTURE DIRECTIONS
Ng looked to the future with a powerful sentiment: “We cannot, and will not, be satisfied with the current status quo.” She called for improvements in clinical care and research efforts for young people with gastrointestinal cancers, with suggestions including more specialised centres, universal germline genetic testing for all young patients, and genomic profiling to identify more therapeutic targets.
Finally, she announced that, ‘Beyond CRC cohort study’, a research effort launched at Dana-Farber Institute, aimed to longitudinally track patients with young-onset CRC. Since its creation in December 2023, their social media platform ‘Count Me In’ has also helped connect with over 400 patients, elevating the recruitment and representation of patient groups.
References
- Yuan C et al. The age-dependent association of risk factors with pancreatic cancer. Ann. Oncol. 2022;33(7):693-701.
