Abstract
The incidence of early-onset colorectal cancer (EOCRC; defined as colorectal cancer diagnosed under the age of 50 years) has been rising in Aotearoa New Zealand, and in many countries around the world for the past three decades. The cause of this are unknown. This thesis has a wide scope, and presents a broad range of research investigating several different facets of EOCRC, including the epidemiology, risk factors, microbiology, molecular biology, diagnosis and treatment, and the psychosocial impacts.
The rising incidence of EOCRC is occurring independently to rates of CRC in older adults, evidenced by rising rates of EOCRC in countries where CRC incidence over the age of 50 years is rising, falling or remaining stable. While the most recently published data from Aotearoa New Zealand (reporting on data up to 2012) identifies significant increases in the rates of distal colonic and rectal cancers in young people, it does not report incidence by ethnicity. This thesis aimed to extend that work by reporting on the recent epidemiology of EOCRC in Aotearoa New Zealand by site of disease, sex and ethnicity, and to make predictions for the future should these trends continue.
The second part of the thesis explored possible causes of rising EOCRC incidence in Aotearoa New Zealand. Epidemiological patterns strongly suggest an environmental cause, however the exact nature of the possible drivers and/or mechanism(s) for the rising incidence of EOCRC remain unknown. To address this, the risk associated with well-known dietary and lifestyle risk factors were investigated in young (under 50 years) and older (over 65 years) CRC patients, compared with age-matched healthy population controls. The intestinal microbiota is increasingly being seen as an interface between the environment and the host, and this was also explored by looking for differences in microbial diversity and/or the abundance of specific microbial taxa in the tumour microbiome of EOCRC and older CRC patients. Further, to complement the study of age-related differences in the tumour microbiome, differential gene expression and consensus molecular subtypes were compared to determine if differences in gene expression might improve understanding of the aetiology of early-onset carcinogenesis.
The third part of the thesis explored the diagnosis and treatment of EOCRC. While the increasing incidence of EOCRC is alarming, the crude incidence rates remain low. This coupled with the fact that the symptoms such as rectal bleeding, altered bowel habit and abdominal pain are common and non-specific, means the diagnosis of EOCRC presents unique challenges. Previous research reports a far longer diagnostic intervals (the time from symptom onset, to diagnosis) in younger compared to older patients, leading to the question as to whether this may be contributing to the later stage of diagnosis seen in EOCRC. In this thesis the pathways to diagnosis and diagnostic intervals were compared between EOCRC, and older patients. The relationship between diagnostic intervals and stage of disease was explored, to determine whether decreasing diagnostic intervals has the potential to improve outcomes, and the role of bowel cancer screening in this population was also considered.
Furthermore, current treatment guidelines do not recommend differing management for EOCRC based on age alone. Despite this, evidence suggests that EOCRC patients are often subjected to more intensive treatment regimens than older patients, with no corresponding improvement in survival. This thesis compared the treatment patterns of EOCRC patients with those of a control group aged 60–74 years, highlighting differences in management and their potential impact on patient outcomes.
The final section of this thesis focused on the psychosocial impacts of EOCRC, a relatively underexplored area that holds particular significance given that younger patients often have many decades of life ahead. A systematic review, which examined the psychosocial effects of EOCRC on patient quality of life (QOL), sexual function, emotional distress, social and family dynamics, career, and financial stability, revealed that EOCRC patients are particularly vulnerable to adverse outcomes in these domains. The review also highlighted a paucity of research in this area. To address this gap, a prospective study compared the QOL impacts of EOCRC with those reported by older patients and explored how these effects evolve over time. The study also assessed the interplay between the physical side effect of treatment and the psychological impacts of a cancer diagnosis, and the flow on effects on patient sexual function. Finally, communication between EOCRC patients and healthcare providers regarding sexual health was examined, identifying perceived barriers from both perspectives. This analysis aimed to develop strategies to improve discussions around sexual health, ultimately enhancing the support provided to EOCRC patients.