Also associated with increased risk of death from any cause in those with the disease

Loneliness and social isolation are linked to a heightened risk of death from cancer as well as from all causes among those with the disease, finds a pooled data analysis of the available research published online in the open access journal BMJ Oncology.

Globally, new cases of cancer are projected to rise to 35 million, and associated deaths to 18.5 million by 2050, note the researchers.

Loneliness is relatively common among people with cancer, and while loneliness is associated with various health issues, including cognitive problems, sleep disorders, immune system dysfunction, and pain, it’s not clear if it might also be linked to a heightened risk of death from cancer, they add.

To explore this further, the researchers scoured research databases for relevant studies published up to September 2024. Out of an initial haul of 148, 16 involving 1,635,051 patients (average age 63) were reviewed, 13 of which were included in a pooled data analysis.

The studies were carried out in Canada, England, Finland, France, Ireland, Japan and the USA and included many different types of cancer.

The potential impact of loneliness (as measured most often by the Social Network Index and UCLA Loneliness Scale) on death from any cause was reported for 1,570,918 patients in 12 studies, and pooled data analysis showed that it was associated with a 34% heightened risk, after adjusting for small study sizes.

The potential impact of loneliness on death from cancer was reported for 2,142,338 patients in nine studies, and pooled data analysis showed that it was associated with an 11% heightened risk of death from the disease, after adjusting for small study sizes.

The three studies excluded from pooled data analysis due to differing outcome measures also consistently reported strong associations between social isolation and a heightened risk of death.

“These findings collectively suggest that loneliness and social isolation may influence cancer outcomes beyond traditional biological and treatment-related factors,” suggest the researchers.

But the variations in study design, methodology, and outcome measures; the limited allowance made for potentially influential factors; and the fact that the included studies were all observational in nature, warrant cautious interpretation of the findings, they highlight.

Nevertheless, they go on to say: “Despite these limitations, our findings are consistent with prior research linking psychosocial stressors to adverse health outcomes. Social isolation and loneliness are thought to increase mortality risk in patients with cancer through interconnected biological, psychological, and behavioural mechanisms.”

They add: “Biologically, the stress response triggered by loneliness may lead to immune dysregulation and heightened inflammatory activity, ultimately contributing to disease progression.”

And they explain: “Psychosocially, the unique burden of cancer survivorship often includes forms of isolation stemming directly from disease and treatment experiences, including the inability of loved ones to fully understand cancer-associated fears, stigma around visible treatment effects, and survivorship-related anxieties.

“Treatment-induced physical changes (fatigue, cognitive impairments) may further limit social participation, while prolonged medicalisation of life can erode pre-illness identity and community connections.”

And they conclude that if the findings are confirmed in further methodologically sound studies, they would indicate the need to routinely incorporate psychosocial assessments and targeted interventions into cancer care to improve outcomes.

14/10/2025

Notes for editors
Research: Impact of loneliness on cancer mortality: a systematic review and meta- analysis Doi: 10.1136/bmjonc-2025-000840
Journal: BMJ Oncology

Link to Academy of Medical Sciences press release labelling system http://press.psprings.co.uk/AMSlabels.pdf

Externally peer reviewed? Yes
Evidence type: Systematic review + meta analysis
Subjects: People

The post Loneliness and social isolation linked to heightened risk of death in those with cancer first appeared on BMJ Group.

May be time to reassess use of PARP inhibitor drugs in these patients, say researchers
Findings pave way for refining genetic testing and personalised treatment in prostate cancer

Mutations in the BRCA1 gene that are either inherited (germline) or acquired (somatic) might not be key to the initiation of prostate cancer, as previously thought, suggests the first study of its kind, published online in the open access journal BMJ Oncology.

If confirmed in further studies, the findings suggest that it may be time to reassess current treatment with PARP (poly(ADP-ribose) polymerase) inhibitor drugs, which block the ability of cells, including cancer cells, to repair DNA damage, in men with BRCA1 genetic variants, say the researchers.

A linked editorial suggests that the findings pave the way for greater refinement of genetic testing and personalised treatment for men with prostate cancer.

Prostate cancer is the most common cancer in men, and genetic variants in DNA damage repair and response genes are known to have a role in disease progression.

For example, men with inherited or acquired mutations in BRCA2 or ATM genes are at heightened risk of aggressive disease and have worse outcomes than those who don’t have these mutations, explain the researchers.

To try and quantify the contribution of inherited and acquired mutations in different DNA repair and response genes in men with prostate cancer, the researchers reviewed the genetic test results of 450 men with the disease in North West England between 2022 and 2024.

The men had either been tested for germline (166), somatic (280), or both types (4) of genetic variants of BRCA1, BRCA2, ATM, CDK12, and PALB2 genes, with a view to starting them on PARP inhibitor treatment.

In 340 cases, the men’s cancer had spread elsewhere (metastasised). Their average age was 69, but ranged between 38 and 87.

Among those in this group who weren’t tested, based on high risk—age or family history—at least 18 (just over 5%) had a germline BRCA2 variant, but only 1 had a germline BRCA1 (0.3%) variant. And of the 263 screened for germline ATM variants, 7(3%) tested positive.

Among the 124 undergoing germline testing based on high risk, their average age was 56 (range 34–77). Again, germline BRCA2 variation predominated, with 8 (8%) testing positive, but only one (less than 1%) testing positive for a germline BRCA1 variant.

Germline BRCA 1 and BRCA 2 test results were available for all 450 men. These revealed 27 germline BRCA2 variants (6%), but only 2 germline BRCA1 variants (0.5%), and one of these probably wasn’t the driver as an ATM mutation was also present, note the researchers.

Six ATM germline variants were found among the 328 men tested for this genetic mutation. And among the 97 men tested for germline PALB2 variants just 1 was found in a man in his 70s with a strong family history of breast cancer.

Of those tested for CHEK2 (122), for Lynch (69), or for RAD51C/D (15) genetic mutations, none was found.

Somatic test results were available for 280 men whose cancer had spread elsewhere.  Overall, 31 (11%) had an identifiable BRCA2 genetic variant. Of these, 16 (6%) were confirmed germline and 11 (4%) were confirmed somatic. Variant type was unclear in 4.

This indicates that BRCA2 variants, somatic and germline, have a major role in prostate cancer progression affecting at least 1 in 10 carriers with the disease, say the researchers.

BRCA1 variants, on the other hand, don’t seem to be major contributors to disease initiation or progression, with only 1 somatic variant and 1 germline variant found in combination with a germline ATM variant in one case where the disease had spread elsewhere.

Both germline and somatic ATM mutations were also associated with disease spread as 16 out of the 263 (6%) tumour samples tested had an ATM genetic variant identified, 5 (2%) of which were germline, 7 (2.5%) of which were somatic, while 4 were indeterminate.

And the data suggest that somatic CDK12 and somatic and germline BRCA2 should no longer be considered mutually exclusive, as they have been previously.

The researchers acknowledge that only 217 tumour samples were tested for all genetic variants, and that they were unable to classify all those identified as either somatic or germline. And as the BRCA1 variant carriers were tested relatively recently, the longer term outcomes for these men aren’t yet known, they point out.

“Even if there is a signal for non-metastatic prostate cancer in BRCA1, this may not justify PSA [prostate specific antigen] screening, given the high rates of overdiagnosis,” say the researchers.

“It may be time, therefore, to question whether BRCA1 should be considered to be a prostate cancer predisposing gene, given its very low prevalence in the present study of somatic mutations,” they suggest.

In a linked editorial, Drs Fumihiko Urabe and Kosuke Takemura, of, respectively, The Jikei University School of Medicine, Minato, Japan, and The Cancer Institute Hospital of JFCR, Tokyo, Japan agree that treatment options may need to be revised in light of the study findings.

“[They] reinforce the role of BRCA2 and ATM as key determinants of aggressive prostate cancer phenotypes. The limited involvement of BRCA1 suggests that tumours harbouring BRCA1 variants may not rely on homologous repair deficiency, potentially limiting their responsiveness to PARP [inhibitor]-based therapies,” write the authors.

They add: “CDK12 mutations, previously considered mutually exclusive with BRCA2, were observed in conjunction with BRCA2 mutations, suggesting a potential for dual targeted therapies combining PARP [inhibitors] and immunotherapy.”

And conferring the same potential for aggressive disease on both BRCA1 and BRCA2 is probably no longer appropriate, they suggest.

“Although many prior clinical studies have categorised BRCA1 and BRCA2 mutations together as a single group (BRCA1/2), this research leads to the conclusion that BRCA1 and BRCA2 should be analysed separately,” they say.

“If post hoc analyses of previous clinical trials that grouped BRCA1/2 mutations reveal differing therapeutic effects, it may necessitate reevaluating the interpretation of BRCA1 and BRCA2 mutations in prostate cancer,” they add.

Although further research in more diverse groups of patients is warranted, the study findings “pave the way for refining genetic testing strategies and personalised treatment approaches in prostate cancer,” they conclude.

25/02/2025

Notes for editors
Research: UK-based clinical testing programme for somatic and germline BRCA1/2, ATM and CDK12 mutations in prostate cancer: first results Doi 10.1136/bmjonc-2024-000592
Editorial: Evaluating the genetic landscape of prostate cancer: new insights from BRCA1/2, ATM and CDK12 mutations Doi: 10.1136/bmjonc-2024-000717

Journal: BMJ Oncology

External funding: Cancer Research UK ACED Alliance Early Detection Centre (research)

Link to Academy of Medical Sciences press release labelling system
http://press.psprings.co.uk/AMSlabels.pdf  

Externally peer reviewed? Yes (research); No (editorial)
Evidence type: Observational
Subjects: People

The post BRCA1 gene mutations may not be key to prostate cancer initiation, as previously thought first appeared on BMJ Group.

Could kickstart new generation of screening tests for early cancer detection, say researchers

A sex-specific panel of 10 proteins can pick up 18 different early stage cancers, representing all the major organs of the human body, finds a proof of concept study published in the open access journal BMJ Oncology. 

The findings could kick-start a new generation of screening tests for early detection of the disease, say the researchers, particularly as there are many sex specific differences in cancer—including age at occurrence, cancer types, and genetic alterations—points out a linked editorial.

Cancer accounts for 1 in every 6 deaths around the globe, with nearly 60% of these deaths caused by cancers for which no screening test exists, note the researchers.

What’s more, even existing screening tests have considerable drawbacks, including invasiveness, expense, and low levels of accuracy for early stage disease, they add.

Specific blood proteins could be used for early detection and ongoing monitoring, but the currently available options lack sensitivity—accuracy of picking up those with cancer—and specificity—accuracy of excluding those without cancer, say the researchers.

To explore the potential use of plasma proteins, including those that are currently barely detectable, as biological signatures of solid tumours in specific organs, the researchers collected plasma samples from 440 people diagnosed with 18 different types of cancer before treatment, and from 44 healthy blood donors.

They then measured more than 3000 proteins strongly associated with cancer chemical pathways in each sample, using a technology deploying antibodies and a statistical algorithm in a 2-step process.

The first step involved detecting the biological signature of any cancer, and the second step involved identifying the tissue of origin and cancer subtypes—small cell and non-small cell cancers of the lung, for example.

Through a process of elimination, a panel of 10 sex specific proteins emerged that were differentially expressed among the plasma samples from cancer patients and healthy people.

The fact that these protein signatures differed significantly between men and women suggests that they are most likely sex-specific for all cancers, say the researchers.

By themselves, each individual protein was only moderately accurate at picking up early stage disease, but when combined with the other proteins in a panel they were highly accurate.

These proteins were able to pick up stage I-III disease and all types of cancer, but were particularly effective at picking up early stage disease.

They identified 93% of stage 1 cancers among the men and 84% of stage 1 cancers among the women, with 99% specificity and 90% sensitivity in the men and 85% sensitivity and 99% specificity in the women.

A panel of 150 proteins were able to identify the tissue of origin of most cancers in more than 80% of cases in both men and women. 

Analysis of the plasma protein amounts showed that almost all of them were present at very low levels, highlighting the importance of low-level proteins to pick up pre-cancerous and early stage disease before a tumour has yet to have any substantial systemic impact, say the researchers.

They acknowledge the relatively small sample size of their study and the lack of information on co-existing conditions, potentially limiting the wider applicability of their findings. And despite advancements in proteomic techniques, the full range of proteins produced by a particular cell or organ isn’t yet known, they add.

Nevertheless they conclude: “Our new generation protein-based plasma test has shown high sensitivity in detecting a variety of early stage tumours in asymptomatic patients, making it a strong candidate for use as a population-wide screening tool that is not currently achievable with existing tests or techniques.” 

In a linked editorial, Dr Holli Loomans-Kropp, of the College of Medicine, The Ohio State University, adds: “Although several problems need to be addressed before MCED [multi-cancer early detection] tests can be deployed at a population scale, a method to improve on current issues of sensitivity and specificity may be use of sex-specific detection panels.”

She continues: “Demonstrable sex-specific differences in cancer—including age of onset, cancer types and genetic alterations—suggest this approach would be useful. 

“The widespread use of MCEDs may be a way down the road, but perhaps employing a strategy like sex-specific MCED panels could get the field moving a little faster.”

Notes for editors
Research: Novel proteomics-based plasma test for early detection of multiple cancers in the general population doi: 10.1136/bmjonc-2023-000073
Editorial: Multi-cancer early detection tests: a strategy for improvement doi: 10.1136/bmjonc-2023-000184
Journal: BMJ Oncology

Funding: None declared

Link to Academy of Medical Sciences press release labelling system
http://press.psprings.co.uk/AMSlabels.pdf

Externally peer reviewed? Yes (research); No (Editorial)
Evidence type: Case-control study
Subjects: People

The post Sex-specific panel of 10 proteins can pick up 18 different early stage cancers first appeared on BMJ Group.

New cases have risen 79%, overall, with fastest rise in windpipe and prostate cancers
Heaviest death toll for cancers of breast, windpipe, lung, bowel, and stomach

There’s been a striking 79% increase in new cases of cancer among the under 50s around the world over the past three decades (1990-2019), finds research published today in the open access journal BMJ Oncology.

Breast cancer accounted for the highest number of ‘early onset’ cases in this age group in 2019. But cancers of the windpipe (nasopharynx) and prostate have risen the fastest since 1990, the analysis reveals. Cancers exacting the heaviest death toll and compromising health the most among younger adults in 2019 were those of the breast, windpipe, lung, bowel, and stomach.

The findings upend received wisdom about the types of cancers typically affecting the under 50s, a linked editorial suggests.

While cancer tends to be more common in older people, the evidence suggests that cases among the under 50s have been rising in many parts of the world since the 1990s. But most of these studies have focused on regional and national differences; and few have looked at the issue from a global perspective or the risk factors for younger adults, say the researchers. 

In a bid to plug these knowledge gaps, they drew on data from the Global Burden of Disease 2019 Study for 29 cancers in 204 countries and regions.

They looked at the incidence (new cases), deaths, health consequences (disability-adjusted life years or DALYs) and contributory risk factors for all those aged 14 to 49 to estimate annual percentage change between 1990 and 2019.

In 2019, new cancer diagnoses among the under 50s totalled 3.26 million, an increase of 79% on the 1990 figure. Overall, breast cancer accounted for the largest number of these cases and associated deaths at 13.7 and 3.5/100,000 of the global population, respectively. 

But new cases of early onset windpipe and prostate cancers rose the fastest between 1990 and 2019, with estimated annual percentage changes of 2.28% and 2.23%, respectively. At the other end of the spectrum, early onset liver cancer fell by an estimated 2.88% every year.

More than 1 million (1.06) under 50s died of cancer in 2019, an increase of just under 28% on the 1990 figure. After cancer of the breast, cancers exacting the highest death toll and subsequent poor health were those of the windpipe, lung, stomach, and bowel, with the steepest increases in deaths among people with kidney or ovarian cancer.

The highest rates of early onset cancers in 2019 were in North America, Australasia, and Western Europe. But low to middle income countries were also affected, with the highest death rates among the under 50s in Oceania, Eastern Europe, and Central Asia.

And in low to middle income countries, early onset cancer had a much greater impact on women than on men, in terms of both deaths and subsequent poor health.

Based on the observed trends for the past three decades, the researchers estimate that the global number of new early onset cancer cases and associated deaths will rise by a further 31% and 21%, respectively, in 2030, with those in their 40s the most at risk. 

Genetic factors are likely to have a role, say the researchers. But diets high in red meat and salt, and low in fruit and milk; alcohol consumption; and tobacco use are the main risk factors underlying the most common cancers among the under 50s, with physical inactivity, excess weight, and high blood sugar contributory factors, the data indicate.

The researchers acknowledge various limitations to their findings: principally, the variable quality of cancer registry data in different countries may have led to under-reporting and under-diagnosis, they suggest. And it’s still not clear to what extent screening and early life exposure to environmental factors may be influencing the observed trends, they add.

But, point out doctors from the Centre for Public Health, Queen’s University Belfast, in a linked editorial: “The findings…challenge perceptions of the type of cancer diagnosed in younger age groups.”

They emphasise: “Full understanding of the reasons driving the observed trends remains elusive, although lifestyle factors are likely contributing, and novel areas of research such as antibiotic usage, the gut microbiome, outdoor air pollution and early life exposures are being explored.” 

They conclude: “Prevention and early detection measures are urgently required, along with identifying optimal treatment strategies for early-onset cancers, which should include a holistic approach addressing the unique supportive care needs of younger patients.” 

They add: “There is a pressing need for partnership, collaboration and resource distribution at a global level in order to achieve these aims.”

05/09/2023

Notes for editors
Research: Global trends in incidence, death, burden and risk factors of early-onset cancer from 1990 to 2019  doi 10.1136/bmjonc-2023-000049
Editorial: Shifting tides: the rising tide of early onset cancers demands attention doi 10.1136/bmjonc-2023-000106
Journal: BMJ Oncology

Funding: (Research) Natural Science Fund for Distinguished Young Scholars of Zhejiang Province; National Nature Science Foundation of China

Link to Academy of Medical Sciences press release labelling system http://press.psprings.co.uk/AMSlabels.pdf

Externally peer reviewed? Yes (research); No (editorial)
Evidence type: Observational (data analysis); Opinion
Subjects: People

The post Global surge in cancers among the under 50s over past three decades first appeared on BMJ Group.