World Cancer Day – An interview with Professor Richard Martin discussing interdisciplinary cancer research

This interview was originally published by PLOS ONE on 3 February 2023.

World Cancer Day, held every 4 February, is a global initiative led by the Union for International Cancer Control (UICC) to raise awareness, improve education and catalyze action. This year’s theme is ‘Close the Care Gap: Uniting our voices and taking action’.

Each year, PLOS ONE publishes more than 1000 cancer-related research articles from authors across the globe. In celebration of this year’s theme, we interview PLOS ONE author Richard Martin, Professor of Clinical Epidemiology at the University of Bristol and co-lead researcher of the Integrative Cancer Epidemiology Programme. We ask how Open Science can contribute to interdisciplinary cancer research and how engagement with patient communities has increased the impact of their research.

PLOS: You are co-lead Principal Investigator of a CRUK programme grant, the Integrative Cancer Epidemiology Programme (ICEP), can you tell us about the aims of this research programme?

RM: Many studies investigating cancer risk factors are observational and subject to bias. The aim of ICEP is to use biological data, primarily data on genetic variation and gene products including proteins or metabolites, along with novel statistical methods to provide high quality evidence on: the causes of cancer; factors influencing cancer progression; new ways to predict who will develop or die from cancers; and new ways to prevent cancer and its progression, including behavioral and therapeutic interventions. We are focusing on cancers that are common, present late or have poor survival rates. This knowledge will facilitate the development of new interventions to detect, diagnose and treat cancers earlier as well as targeting prevention measures to those most at risk. Patient and public involvement, communication and knowledge exchange is embedded in the programme – we seek input from a “User Reference Group” on all aspects of research study design, particularly on patient and public facing materials.

PLOS: Can you tell us about any exciting projects coming out of ICEP?

RM: Previous studies investigating the role of obesity in cancer risk using classical epidemiological methods have likely downplayed the role of obesity in cancer risk and progression. Our understanding of the major role of obesity and obesity-related mechanisms in cancer development is increasing thanks to the use of newer epidemiological methods such as Mendelian randomization, which suggests that the estimated cancer burden (e.g. 6% in the UK) associated with overweight and obesity may be substantially underestimated: the magnitude of the relative risk when using genetic markers of obesity is about twice as high for several cancers as opposed to a one-off measure of obesity (e.g. body mass index). Genetic data also suggest that obesity may have a causal role in other cancers not previously linked to adiposity, including lung cancer. We have previously published a study of metabolic factors and risk of histological types of lung cancer in PLOS ONE. Here, the Mendelian randomization study design enabled us to interrogate the role of metabolic conditions on lung cancer risk stratified by smoking status to reveal (at that time) novel evidence that genetic susceptibility to obesity influences lung cancer through behavioral effects on smoking patterns. We are now diving deeper into potential mechanisms linking obesity with cancer risk, focusing on the role of insulin and glucose.

PLOS: What are the main challenges facing the interdisciplinary field of cancer research?

RM: Our work relies on successful collaboration between experts in epidemiology, biochemistry, clinical practice, engineering and many other disciplines. One major challenge in working across research disciplines is a mutual understanding of what is driving each discipline, their priorities, and also the barriers in understanding each other’s technical language. Epidemiologists (in general) are concerned with creating robust study designs within free-living populations – ensuring sufficient sample sizes for adequate study power, reducing biases and the relevance of research findings to human populations. This can sometimes conflict, for example, with a biochemist’s interest in uncovering mechanistic understanding, working within rigorously controlled experimental settings. From experience, I can confidently say that epidemiologists can quickly get lost in front of presentations describing biochemical pathways! One possible solution is joint training or placements across research disciplines from an early career stage, along with funders stating the need for this type of work.

PLOS: How do you think open science can help with overcoming these challenges?

RM: Triangulation of research findings – using multiple datasets and methods, each with their own set of biases and limitations, to approach a research question – is critically important to enhance confidence in conclusions. This is because different methods leading to the same results give more confidence in the research findings. If papers and data are Open Access, this facilitates this process of triangulation. It is also vitally important to share ‘null’ findings so that attempts to investigate the mechanisms behind associations observed in populations can be appropriately prioritized.

PLOS: What major improvements in clinical decision making related to cancer have you seen during your career?

RM: In my area of interest (primary and secondary prevention), an important step has been the recognition of the need for randomized controlled trial evidence before introducing a new screening program. We added to the evidence on prostate cancer screening and in 2018 we published results from the Cluster Randomized Trial of PSA Testing for Prostate Cancer (CAP). In this trial primary care practices across the UK were randomized to a single PSA screening intervention or standard practice without screening. We found no meaningful difference in prostate cancer mortality after a median follow-up of 10 years, but did show in a linked trial a range of adverse effects related to biopsy and treatment. Further, more men who had a one off PSA test were diagnosed with low risk prostate cancer that would probably not progress or need treatment – potentially causing unnecessary anxiety. Although longer-term follow-up is under way, these results indicate that the harms are likely to outweigh any potential benefits of screening for prostate cancer using a single PSA test, a conclusion that has been accepted by many policy making bodies around the world.

PLOS: Other than your own research focus, what do you think is the most exciting area in cancer research at the moment?

RM: Although exciting progress has been made in the field of immunotherapy, the treatment of cancer is generally very expensive for the number of life years gained. There is huge benefit to be realized in understanding the mechanisms of cancer initiation and in improving early detection so that cancers with the potential to progress can be diagnosed and treated sooner, before they cause symptoms, and before they become difficult to treat. This is evidenced for example by the success of human papillomavirus (HPV) vaccination in cervical cancer prevention, which will also be seen for other HPV related cancers and important advances in screening for esophageal, bowel and lung cancer. It would be great to see greater advances in behavioral interventions and policies designed to prevent cancer, and there are likely to be a wide range of ubiquitous carcinogens (e.g “everywhere and forever” chemicals, climate, water, infectious agents, indoor/outdoor air pollution, social stressors) that we are yet to fully understand.