Showing papers by "Cancer Research UK published in 2021"

Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction

Abstract: Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84–5.29) for men of European ancestry to 3.74 (95% CI, 3.36–4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14–2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71–0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction.

The Impact of COVID-19 on Cancer Symptom Experience and Help-Seeking Behaviour in the United Kingdom: A Cross-Sectional Population Survey

Abstract: Background: The impact of COVID-19 on timely symptomatic diagnosis of cancer is likely to be considerable. We examined symptom help-seeking behaviour in the UK population during the pandemic. Methods: A population-based sample of 7,543 UK adults aged 18+ was recruited online between August and September 2020. Measures included experiences and perceptions of 15 potential cancer symptoms, help-seeking barriers and behaviour. Multivariable logistic regression was used to model correlates of help-seeking behaviour in participants who experienced at least one potential cancer symptom during the previous six months. Qualitative interviews were conducted with a purposive sample of 30 survey participants and analysed thematically. Findings: Frequently endorsed help-seeking barriers included worries about wasting the doctor’s time (15·4%), putting strain on healthcare services (12·6%) and not wanting to be seen making a fuss (12·0%). Of 3,025 (40·1%) participants who experienced a potential cancer symptom, 44·8% (1,355/3,025) had not contacted their General Practitioner (GP). Odds of seeking help were higher among participants with disability (95% CI 1·11-1·71, aOR=1·38) and who experienced more potential cancer symptoms (95% CI 1·56-1·82, aOR=1·68) and lower among those who perceived COVID-19 as the cause of symptom(s) experienced (95% CI 0·25-0·52, aOR=0·36). Qualitative data revealed a reluctance to contact the GP due to concerns about catching or transmitting COVID-19. Participants were fearful of seeking help in hospitals and described putting their health concerns on hold to avoid burdening healthcare services. When experienced, remote GP consultations were well received. Interpretation: Many people stayed away from healthcare services during the first six months of the UK pandemic, despite experiencing potential cancer symptoms. National campaigns are needed to signal that cancer cannot wait and that services are open safely for those with unusual or persistent symptoms. Trial Registration: ISRCTN17782018 Funding Statement: Economic and Social Research Council as part of UK Research and Innovation’s Rapid Response to COVID-19 (ES/V00591X/1). Declaration of Interests: The authors declare no conflict of interest. Ethics Approval Statement: Ethical approval was granted by the School of Medicine Research Ethics Committee, Cardiff University (ref 20.68).

A conservative finite element ALE scheme for mass-conservative reaction-diffusion equations on evolving two-dimensional domains

Abstract: Mass-conservative reaction-diffusion systems have recently been proposed as a general framework to describe intracellular pattern formation. These systems have been used to model the conformational...

Impact of COVID-19 pandemic on weight and BMI among UK adults: a longitudinal analysis of data from the HEBECO study

Abstract: BackgroundCOVID-19-related restrictions impacted weight and weight-related factors during the initial months of the pandemic. However, longitudinal analyses are scarce. MethodsAn online, longitudinal study was conducted among self-selected UK adults (n=1,818), involving three surveys during 2020 (May-June, August-September, November-December), covering height, weight and sociodemographic, COVID-19-related and behavioural measures. Data were analysed using generalised estimating equations. ResultsSelf-reported average weight and body mass index (BMI) significantly increased from May-June to August-September (74.95kg to 75.33kg, 26.22kg/m2 to 26.36kg/m2, both p<0.001), and then significantly decreased to November-December (to 75.06kg, 26.27kg/m2, both p<0.01), comparable to May-June levels (p=0.274/0.204). However, there was great interindividual variation, with 37.0%/26.7% reporting an increase and 34.5%/26.3% reporting a decrease in weight/BMI greater than 0.5kg/0.5kg/m2, respectively from May-June to November-December. The average weight/BMI increase was 3.64kg (95% confidence interval: 3.32,3.97)/1.64kg/m2 (1.49,1.79), and the average weight/BMI decrease was 3.59kg (3.34,3.85)/1.53kg/m2 (1.42,1.63). In fully adjusted models, increase in weight/BMI across surveys was significantly negatively associated with initial BMI, and positively associated with monthly high fat, salt and sugar (HFSS) snacks intake and alcohol consumption, and for BMI only, older age. However, associations were time-varying, such that lower initial BMI, higher HFSS snacks intake and high-risk alcohol consumption were associated with maintenance of increased weight/BMI from August-September to November-December. ConclusionThe average weight/BMI of UK adults increased during the early pandemic months, before returning to baseline levels in November-December 2020. However, this masks substantial interindividual variation in weight/BMI trajectories, indicating vulnerabilities associated with changes in food and alcohol consumption throughout the pandemic. What is currently known from previous studiesO_LISmall increases in average weight/BMI have been reported (1.57kg/0.31kg/m2) during the initial three months of the pandemic. C_LIO_LIChanges in weight/BMI during the early months were not uniform, with significant proportions increasing (11.2-72.4%) as well as decreasing (7.2-51.4%) weight/BMI. C_LIO_LIWeight/BMI change has been associated with several sociodemographic, lifestyle and behavioural factors. C_LIO_LIWhether these weight/BMI changes persist over longer durations of the pandemic, and the factors associated with any long-term weight/BMI change is largely unknown. C_LI What this paper addsO_LIIn UK adults, average weight/BMI first increased and then decreased from May to December 2020 during the pandemic, but this masks large interindividual variability in average changes. C_LIO_LIInitial BMI at the start of the pandemic and health behavioural factors such as alcohol consumption and high fat, salt and sugar (HFSS) snacks intake were significantly associated with a change in weight/BMI. C_LIO_LIThe strength of the association of alcohol consumption, initial BMI and HFSS snacks intake with weight/BMI change was dependent on the stage of the pandemic, with more pronounced differences becoming apparent during the latter part of 2020. C_LI

Publisher Correction: Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction (Nature Genetics, (2021), 53, 1, (65-75), 10.1038/s41588-020-00748-0)

Abstract: In the version of this article originally published, the names of the equally contributing authors and jointly supervising authors were switched. The correct affiliations are: “These authors contributed equally: David V. Conti, Burcu F. Darst. These authors jointly supervised this work: David V. Conti, Rosalind A. Eeles, Zsofia Kote-Jarai, Christopher A. Haiman.” The error has been corrected in the HTML and PDF versions of the article.

Impact of COVID-19 pandemic on diet behaviour among UK adults: a longitudinal analysis of the HEBECO study

Abstract: COVID-19 pandemic restrictions impacted dietary habits during the initial months of the pandemic, but long-term effects are unclear. In this longitudinal study, self-selected UK adults (n=1,733) completed three online surveys (May-June, August-September and November-December 2020, with a retrospective pre-pandemic component in the baseline survey), self-reporting sociodemographics, lifestyle and behaviours, including high fat, salt and sugar (HFSS) snacks, HFSS meals and fruit and vegetable (FV) intake. Data were analysed using generalised estimating equations. Monthly HFSS snacks portion intake increased from pre-pandemic levels (48.3) in May-June (57.6, p<0.001), decreased in August-September (43.7, p<0.001), before increasing back to pre-pandemic levels in November-December (49.2, p<0.001). 48.5% self-reported increased (25.9 [95% confidence interval: 24.1, 27.8]) and 47.7% self-reported decreased (24.1 [22.4,26.0]) monthly HFSS snacks portion intakes in November-December compared with pre-pandemic levels. Monthly HFSS meals portion intake decreased from pre-pandemic levels (7.1) in May-June (5.9, p<0.001), being maintained in August-September (5.9, p=0.897), and then increasing again in November-December (6.6, p<0.001), to intakes that remained lower than pre-pandemic levels (p=0.007). 35.2% self-reported increased (4.8 [4.3, 5.3]) and 44.5% self-reported decreased (5.1 [4.6,5.6]) monthly HFSS meals portion intakes in November-December compared with pre-pandemic levels. The proportion meeting FV intake recommendations was stable from pre-pandemic through to August-September (70%), but decreased in November-December 2020 (67%, p=0.034). Increased monthly HFSS snacks intake was associated with female gender, lower quality of life, and - in a time-varying manner - older age and higher HFSS meals intake. Increased monthly HFSS meals intake was associated with female gender, living with adults only and higher HFSS snacks intake. Reduced FV intake was associated with higher body mass index (BMI) and lower physical activity. These results suggest large interindividual variability in dietary change during the first year of the pandemic, with important public health implications in individuals experiencing persistent increases in unhealthy diet choices, associated with BMI, gender, quality of life, living conditions, physical activity and other dietary behaviours. What is currently known from previous studiesO_LIThe introduction of lockdown restrictions impacted on diet behaviours during the initial months of the pandemic. C_LIO_LIChanges in dietary behaviours have been wide ranging, with individuals making healthy and unhealthy dietary changes in high fat, salt and sugar (HFSS) snacks, HFSS meals and fruit and vegetable (FV) intake. C_LIO_LIThese dietary changes are associated with multiple sociodemographic, lifestyle and behavioural factors. C_LIO_LIWhether dietary changes persist across longer periods of the pandemic, and which factors are associated with any long-term dietary behaviour change is yet to be identified. C_LI What this paper addsO_LIAverage UK adult intakes of HFSS snacks and meals fluctuated across the pandemic, with the former returning to pre-pandemic levels and the latter remaining below pre-pandemic levels. C_LIO_LIFV intake was stable until the end of 2020, when the proportion meeting recommended intakes declined. C_LIO_LIAcross the first year of the pandemic, being female and having a lower quality of life were associated with an increase in HFSS snacks intake, whereas the association of age and HFSS meals intake with HFSS snacks intake varied across the pandemic. Living with adults only and having a higher intake of HFSS snacks were associated with an increase in HFSS meals intake. A higher BMI and lower physical activity level were associated with reduced FV intake. C_LI

Open letter to the prime minister and secretary of state on the second anniversary of England's announcement that it would be smoke-free by 2030.

Abstract: Two years ago today the government announced its ambition to make England smoke-free by 2030.12 This includes making smoked tobacco obsolete, with smokers quitting or moving to reduced risk products like e-cigarettes. Despite acknowledging that it would be “extremely challenging,” there is still no sign to date of the “bold action” the government promised to deliver this crucial public health objective. Although we are a world leader in tobacco control, the current rate of decline in smoking is insufficient to deliver the ambition.3 Indeed, since it was announced over 200 000 children under 16 in England have started smoking,4 two thirds of …

Hotspot ESR1 mutations are multimodal and contextual drivers of breast cancer metastasis

Abstract: Constitutively active estrogen receptor- (ER/ESR1) mutations have been identified in approximately one third of ER+ metastatic breast cancer. Although these mutations are known mediators of endocrine resistance, their potential role in promoting metastatic disease has not yet been mechanistically addressed. In this study, we show the presence of ESR1 mutations exclusively in distant, but not local recurrences. In concordance with transcriptomic profiling of ESR1 mutant tumors, genome-edited Y537S and D538G cell models have a reprogrammed cell adhesive gene network via alterations in desmosome/gap junction genes and the TIMP3/MMP axis, which functionally confers enhanced cell-cell contacts while decreased cell-ECM adhesion. Context-dependent migratory phenotypes revealed co-targeting of Wnt and ER as vulnerability. Mutant ESR1 exhibits non-canonical regulation of several metastatic pathways including secondary transactivation and de novo FOXA1-driven chromatin remodeling. Collectively, our data supports evidence for ESR1 mutation-driven metastases and provides insight for future preclinical therapeutic strategies. SignificanceContext and allele-dependent transcriptome and cistrome reprogramming in genome-edited ESR1 mutation cell models elicit diverse metastatic phenotypes, including but not limited to alterations in cell adhesion and migration. The gain-of-function mutations can be pharmacologically targeted, and thus may be key components of novel therapeutic treatment strategies for ER-mutant metastatic breast cancer.