British scientists have suggested that proteins in the blood could warn people of cancer more than seven years before diagnosis, according to their research.
The University of Oxford team studied blood samples from more than 44 000 people in the UK Biobank, including more than 4 900 people who subsequently had a cancer diagnosis.
They compared the proteins of people who did and did not go on to be diagnosed with cancer and identified 618 proteins linked to 19 types of cancer, including colon, lung, non-Hodgkin lymphoma and liver, reports The Guardian.
The study, funded by Cancer Research UK and published in Nature Communications, also found 107 proteins associated with cancers diagnosed more than seven years after the patient’s blood sample was collected, and 182 proteins that were strongly associated with a cancer diagnosis within three years.
The authors concluded that some of these proteins could be used to detect cancer much earlier and potentially provide new treatment options, though further research was needed.
Dr Keren Papier, a senior nutritional epidemiologist at Oxford Population Health at the University of Oxford and joint first author of the study, said: “To save more lives from cancer, we need to better understand what happens at the earliest stages of the disease … (and) how the proteins in our blood can affect our risk of cancer. Now we need to study these proteins in depth to see which ones could be reliably used for prevention.”
A second linked study looking at genetic data from more than 300 000 cancer cases found 40 proteins in the blood that influenced someone’s risk of getting nine types of cancer. While altering these proteins may increase or decrease the chances of someone developing cancer, in some cases this could lead to unintended side effects, the authors found.
Dr Karl Smith-Byrne, senior molecular epidemiologist at Oxford Population Health and a senior author of the first paper and first author of the second study, said: “We’ve predicted how the body might respond to drugs that target specific proteins, including many potential side effects. Before any clinical trials take place, we have some early indications of which proteins we might avoid targeting because of unintended side effects.
“This research brings us closer to being able to prevent cancer with targeted drugs – once thought impossible but now much more attainable.”
Professor Ruth Travis, senior molecular epidemiologist at Oxford Population Health and a senior author of both studies, said: “To be able to prevent cancer, we need to understand the factors driving the earliest stages of its development. These studies are important because they provide many new clues about the causes and biology of multiple cancers, including insights into what’s happening years before a cancer is diagnosed.”
Mark Lawler, the chair in translational cancer genomics and professor of digital health at Queen’s University Belfast, said: “The data are impressive – finding evidence of cancer before it has manifested itself clinically provides a critical window of opportunity to treat with a greater chance for success, or even more importantly, to achieve the holy grail of preventing cancer before it can even occur.
“More work needs to be done, but this is an important step forward in a disease that affects one in two of UK citizens during their lives.”
Study 1 details
Identifying proteomic risk factors for cancer using prospective and exome analyses of 1463 circulating proteins and risk of 19 cancers in the UK Biobank
Keren Papier, Joshua Atkins, Ruth Travis et al.
Published in Nature on 15 May 2024
Abstract
The availability of protein measurements and whole exome sequence data in the UK Biobank enables investigation of potential observational and genetic protein-cancer risk associations. We investigated associations of 1463 plasma proteins with incidence of 19 cancers and 9 cancer subsites in UK Biobank participants (average 12 years follow-up). Emerging protein-cancer associations were further explored using two genetic approaches, cis-pQTL and exome-wide protein genetic scores (exGS). We identify 618 protein-cancer associations, of which 107 persist for cases diagnosed more than seven years after blood draw, 29 of 618 were associated in genetic analyses, and four had support from long time-to-diagnosis ( > 7 years) and both cis-pQTL and exGS analyses: CD74 and TNFRSF1B with NHL, ADAM8 with leukaemia, and SFTPA2 with lung cancer. We present multiple blood protein-cancer risk associations, including many detectable more than seven years before cancer diagnosis and that had concordant evidence from genetic analyses, suggesting a possible role in cancer development.
Study 2 details
Identifying therapeutic targets for cancer among 2074 circulating proteins and risk of nine cancers
Joshua Atkins, Ricardo Cortez Penha, James McKay et al.
Published in Nature on 29 April 2024
Abstract
Circulating proteins can reveal key pathways to cancer and identify therapeutic targets for cancer prevention. We investigate 2,074 circulating proteins and risk of nine common cancers (bladder, breast, endometrium, head and neck, lung, ovary, pancreas, kidney, and malignant non-melanoma) using cis protein Mendelian randomisation and colocalisation. We conduct additional analyses to identify adverse side-effects of altering risk proteins and map cancer risk proteins to drug targets. Here we find 40 proteins associated with common cancers, such as PLAUR and risk of breast cancer [odds ratio per standard deviation increment: 2.27, 1.88-2.74], and with high-mortality cancers, such as CTRB1 and pancreatic cancer [0.79, 0.73-0.85]. We also identify potential adverse effects of protein-altering interventions to reduce cancer risk, such as hypertension. Additionally, we report 18 proteins associated with cancer risk that map to existing drugs and 15 that are not currently under clinical investigation. In sum, we identify protein-cancer links that improve our understanding of cancer aetiology. We also demonstrate that the wider consequence of any protein-altering intervention on well-being and morbidity is required to interpret any utility of proteins as potential future targets for therapeutic prevention.
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