Amanda J. Cross

Background: The English National Health Service Lynch syndrome-Bowel Cancer Screening Programme (LS-BCSP) which launched in 2023 is a novel, nationally coordinated, quality-assured surveillance programme. We report the first two-year outcomes from the LS-BCSP, evaluating colonoscopy quality and colorectal neoplasia detection rates stratified by patient factors.Methods: LS patients are captured in a national LS registry maintained by the National Disease Registration Service (NDRS), which informs the LS-BCSP. Programme data were extracted to evaluate colonoscopy quality indicators and detection rates for adenoma (ADR), advanced adenoma (AADR), serrated lesions (SLDR), and colorectal cancer (CRCDR). Factors associated with uptake and neoplasia outcomes were assessed using multivariable logistic regression.Findings: Between July 2023 and September 2025, 5933/8327 (71.2%) eligible LS individuals attended a diagnostic test. Median age was 51 (IQR 40-61) years and 58.7% were female. Gene variants comprised MLH1 (25.0%), MSH2/EPCAM (33.7%), MSH6 (26.1%) and PMS2 (15.2%). Diagnostic test uptake improved with lower socio-economic deprivation but was unexpectedly lower among MLH1/MSH2 carriers.Overall, 5900 episodes comprising 6192 colonoscopies were analysed. Complete colonoscopies, adequate bowel preparation and adequate tolerance were achieved in 98.7%, 97.6% and 95.7% of procedures, respectively. ADR, AADR, SLDR, and CRCDR were 33.4%, 5.5%, 28.2% and 1.4%, respectively. Of 88 CRCs diagnosed among 83 patients, 62.5% were Stage I-II.Increasing age, male sex, gene variant, BMI≥30kg/m2, and current smoking were independently associated with adenoma and advanced adenoma detection. Furthermore, increasing age (OR=1.03, 95%CI:1.01-1.05), male sex (OR=1.83, 95%CI:1.20-2.83), and MLH1 (OR=13.55, 95%CI:4.15-83.68) and MSH2/EPCAM (OR=10.30, 95%CI:3.14-63.20) variants were associated with CRC detection.Interpretation: The world’s first quality-assured national LS surveillance programme with ascertainment from a national LS registry demonstrates that high-quality colonoscopy can be delivered consistently at population-level, achieving completion, bowel preparation and tolerance rates >95%. Early LS-BCSP outcomes establish internationally relevant benchmarks for quality and neoplasia detection in LS.

Background: Processed meat and unprocessed red meat are considered carcinogenic and ‘probably carcinogenic’ to humans, respectively, but findings for bladder cancer remain inconsistent. Objectives: We assessed associations between processed meat and unprocessed red meat intake and bladder cancer risk using data from the Pooling Project of Prospective Studies of Diet and Cancer. Methods: Associations with bladder cancer risk were assessed using individual-level data from 30 cohort studies from North America, Europe, Australia and Asia. Diet was assessed at enrolment using validated food frequency questionnaires or diet histories. Following a pre-specified analysis plan, study- and sex-specific hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox regression, adjusted for smoking status and duration and other potential confounders, and pooled using inverse-variance-weighted random-effects meta-analysis. Results: During median follow-up across cohorts of 8–29 years, among 2,575,971 participants, 20,780 were diagnosed with bladder cancer. Processed meat intake was associated with increased bladder cancer risk (HR comparing ≥40 with <5 g/day = 1.08; 95% CI: 1.02–1.15; HR per 20 g/day = 1.02; 95% CI: 1.00–1.03). Weaker evidence of association with increased risk was also observed for unprocessed red meat (HR comparing ≥100 with <20 g/day = 1.06; 95% CI: 1.00–1.13; HR per 50 g/day = 1.01; 95% CI: 0.99–1.03). There was no evidence of heterogeneity by study, sex, or region. Conclusions: Higher intakes of processed meat and unprocessed red meat were associated with a small increase in risk of bladder cancer. These findings are consistent with existing public health recommendations to limit consumption of red and processed meat.

Summary: Background: Sugar sweetened beverages (SSBs), artificially sweetened beverages (ASBs), and fruit and vegetable juices are consumed worldwide, yet their associations with cancer remain unclear. Methods: Within World Cancer Research Fund International’s Global Cancer Update Programme (CUP Global), we conducted a systematic review by searching PubMed and Embase until September 2024 for cohort studies of SSBs, ASBs, and juices and cancer risk. Meta-analyses were conducted to calculate the relative risks (RRs) and 95% CIs per 1 serving/day (355 mL for SSBs/ASBs; 177 mL for juices). Evidence was graded by the CUP Global Expert Panel. The CUP Global standard protocol was registered at: https://osf.io/7utbm/ . Findings: We identified 158 publications from 51 cohorts. There was evidence of a probable causal positive association for SSBs, including carbonated SSBs, with pancreatic cancer incidence (RR 1.09 [95% CI 1.01–1.16]; I ² =8%, n=18 studies), and for SSBs with colorectal cancer incidence (RR 1.07 [95% CI 1.00–1.14]; I ² =41%, n=13). Limited suggestive evidence supported positive associations of SSBs with ovarian (RR 1.61 [95%CI 1.03–2.53]; I ² =0%, n=2), endometrial (RR 1.21 [95%CI 1.03-1.42]; I ² =0%, n=3), and postmenopausal breast cancer incidence (RR 1.05 [95%CI 1.00-1.10] ; I ² =0%, n=6), and of carbonated ASBs with leukaemia incidence (RR 1.29 [95%CI 1.01-1.64]; I ² =0%, n=2). There was evidence of a probable causal positive association for orange juice with different types of skin cancer including melanoma (RR 1.21 [95%CI 1.08-1.34]; I ² =0%, n=4), and basal (RR 1.12 [95%CI 1.06-1.17]; I ² =46%, n=2) and squamous cell carcinoma (RR 1.13 [95%CI 1.04-1.24]; I ² =0%, n=2). An interactive evidence platform is available at: https://teacup.cc.ic.ac.uk/soft-drinks-cancer.html . Interpretation: This review provides evidence supporting probable causal associations of SSBs with pancreatic and colorectal cancers, and of orange juice with skin cancers, with additional suggestive evidence for SSBs with other obesity-related cancers, extending concerns about sugary drink consumption beyond cardiometabolic health to cancer risk. Funding: World Cancer Research Fund network of charities (American Institute for Cancer Research; World Cancer Research Fund; Wereld Kanker Onderzoek Fonds).

Background: The 2018 World Cancer Research Fund (WCRF)/American Institute for Cancer Research Third Expert Report (TER) on diet, adiposity, physical activity and risk of 19 cancers could be enhanced with new data. A framework is needed to prioritize future systematic reviews. Methods: We searched PubMed (January 2019-February 2024) for meta-analyses, pooled analyses, randomized controlled trials (RCTs), Mendelian randomization (MR) studies, and large (>100,000 participants) cohort studies. We assessed TER findings using conditional power (CP) and fail-safe number (FSN) statistics. We developed an exposure-based prioritization score (PS) by awarding or subtracting points considering the quantity, statistical significance, direction, and novelty of associations. Results: We compared 366 meta-analyses, 121 pooled analyses, 19 RCTs, 174 MR studies, and 391 cohort studies covering 151 exposures and 28 cancers with 1,371 TER meta-analyses. Based on CP, non-significant TER associations likely to become significant with additional evidence included folate and colorectal, waist circumference and lung, total fat and ovarian, tea and ovarian, and red meat and kidney cancers. The FSN indicated that most significant TER associations are unlikely to change with additional evidence. The median PS was 6 (range: −15 to 163), with top scores observed for anthropometric measurements (PS _height =40 to PS _BMI =163), physical activity (PS=100), sedentary behavior (PS=64), alcohol (PS=52), tea (PS=36), dietary fiber (PS=31), milk/dairy (PS=29), micronutrients (PS _retinol =27 to PS _iron =38), vitamins (PS _B12 =22 to PS _vitD =91), soy (PS=24), isoflavones (PS=23), and sugar-sweetened beverages (PS=22). Conclusions and Impact: The prioritization framework can help identify impactful systematic reviews to complement TER conclusions and enhance our understanding of emerging research.

Background: Obesity is a growing global epidemic, contributing to heightened risks of multiple chronic diseases, including cancer. Evidence links obesity to several malignancies, including upper gastrointestinal cancers such as oesophageal, gastric, and liver. As the need for effective weight loss intensifies, bariatric surgery is increasingly performed, and procedures have evolved, with Roux-en-Y gastric bypass and sleeve gastrectomy being the most commonly performed surgeries. Given the physiological changes after surgery, the authors conducted a systematic review and meta-analysis to examine the impact of bariatric surgery on upper gastrointestinal cancers. Methods: Eligible studies investigating bariatric surgery and upper gastrointestinal cancer incidence were identified through MEDLINE, Embase, and citation tracking up to July 2025. Studies reporting on oesophageal, gastric, liver, pancreatic, gallbladder, biliary tract, or small intestinal cancer were included. Random-effects models were used to estimate pooled relative risks (RR) and 95% confidence intervals. Results: Across 20 included studies, including 1,173,113 patients undergoing bariatric surgery and 4,600,719 patients not undergoing surgery, bariatric surgery, compared with no surgery, was inversely associated with overall upper gastrointestinal cancer risk (RR 0.58, 95% confidence interval (c.i.) 0.48 to 0.71). Specifically, inverse associations were observed for oesophageal (RR 0.63, 95% c.i. 0.40 to 0.98), liver (RR 0.47, 95% c.i. 0.35 to 0.61), and gallbladder cancer (RR 0.33, 95% c.i. 0.17 to 0.65). No significant associations were found for gastric or pancreatic cancers. There were too few studies for biliary tract and small intestinal cancers to allow meta-analyses. Conclusion: Bariatric surgery appears to reduce the risk of oesophageal, liver, and gallbladder cancers, supporting a role in both weight management and cancer prevention. Standardization in reporting surgical procedures is needed to clarify effects by bariatric surgery type.

Objectives: Colorectal cancer screening with flexible sigmoidoscopy focuses on the distal colorectum, but it is unclear which distal polyp characteristics are associated with future proximal colon cancer incidence. We examined associations between distal adenoma or hyperplastic polyp characteristics and long-term incident proximal colon cancer. Methods: In secondary, observational analyses of UK Flexible Sigmoidoscopy Screening Trial data, we obtained data on the number and size of distal hyperplastic polyps (n=4872) and adenomas (n=4581), adenoma histology and dysplasia from endoscopy and pathology reports for screened asymptomatic participants. Adjusted HRs and 95% CIs for the association between distal polyp characteristics and proximal colon cancer incidence were estimated using multivariable Cox proportional hazard models. Results: Over a median of 20.7 years of follow-up (IQR 16.5–21.7), 110 proximal colon cancers were diagnosed among participants with distal adenomas and 96 were diagnosed among those with only distal hyperplastic polyps detected at baseline. Larger adenoma size (6–9 mm vs ≤5 mm: HR 1.67 (95%CI: 1.07 to 2.59) and ≥10 mm vs ≤5 mm: HR 2.08 (95%CI: 0.98 to 4.43); p=0.037) and high-grade (vs low-grade) adenoma dysplasia (HR 2.82, 95% CI: 1.34 to 5.93; p=0.012) at baseline were positively associated with proximal colon cancer incidence. No associations were observed for distal adenoma number overall or histology, or the number or size of hyperplastic polyps and proximal colon cancer incidence. Conclusions: We found some evidence that larger distal adenomas and those with high-grade dysplasia at baseline were positively associated with proximal colon cancer incidence. Larger studies are needed to confirm these findings. Trial registration number: ISRCTN28352761 .

Background Recommendations for the first postpolypectomy surveillance colonoscopy (SC1), based on stratifying postpolypectomy colorectal cancer (CRC) risk, are well established. Limited data inform recommendations for surveillance beyond SC1. Objective We investigated which patient groups need surveillance beyond SC1. Design Retrospective analysis of patients who underwent colonoscopy with polypectomy at 17 UK hospitals, mostly from 2000 to 2010, and had ≥1 surveillance colonoscopies. Cancer and death data were collected through 2017. We examined patients in groups defined by risk at baseline and SC1, applying risk definitions from the 2020 UK postpolypectomy surveillance guidelines: ‘low risk, low risk’ (LR-LR), ‘high risk, low risk’ (HR-LR), ‘low risk, high risk’ (LR-HR) and ‘high risk, high risk’ (HR-HR). We examined CRC incidence after SC1, censoring at any second surveillance colonoscopy (SC2), and after SC2 through end of follow-up. We compared incidence with general population incidence using standardised incidence ratios (SIRs). Results Analyses included 10 508 patients: LR-LR=6587 (63%), HR-LR=3272 (31%), LR-HR=248 (2%) and HR-HR=401 (4%). Median follow-up from SC1 was 8.0 years and 151 CRCs were diagnosed. Compared with the general population, CRC incidence after SC1 was lower in the LR-LR group (SIR 0.48, 95% CI 0.34 to 0.67), non-significantly different in the HR-LR (SIR 1.17, 0.85 to 1.58) or LR-HR (SIR 2.51, 0.81 to 5.85) groups, but higher in the HR-HR group (SIR 2.84, 1.30 to 5.39). After SC2, CRC incidence in the HR-HR group was no longer higher than in the general population (SIR 1.86, 0.89 to 3.42). Conclusion Patients with high-risk findings at both baseline and SC1 needed an SC2, while those with low-risk findings at SC1 did not, regardless of their baseline findings.

Objective: Colorectal cancer (CRC) screening enables resection of polyp precursor lesions, preventing cancer or detecting it earlier. Post-polypectomy, people can remain at increased CRC risk, prompting surveillance colonoscopy. Less invasive faecal immunochemical tests (FIT) could reduce the burden of surveillance colonoscopy. We investigated whether changes in FIT values over multiple rounds were associated with advanced colorectal neoplasia (ACN) detection. Methods: A cohort of men and women aged 60–72 years deemed intermediate risk by the 2002 UK adenoma surveillance guidelines and scheduled for three yearly colonoscopies were recruited (January 2012–December 2013) within the English Bowel Cancer Screening Programme and offered a quantitative FIT at 1, 2 and 3 years post-baseline colonoscopy for a prospective analysis within a diagnostic accuracy study. Participants positive (≥40 µg haemoglobin/g faeces) at 1 year or 2 years were offered early colonoscopy and excluded, otherwise, colonoscopy was offered at 3 years. Only those who completed three FIT rounds and attended the 3-year colonoscopy were included. Participants were grouped based on changes between FIT rounds, with changes defined as absolute differences ≥4 µg/g, and positivity at round 3. Results: Among 4412 participants, the largest group (n=2773) was the no change category, which had the lowest ACN detection rate (4.7%, 95% CI: 3.9 to 5.5). The serial increase group with a positive round 3 value (n=46) had the highest ACN detection rate (32.6%, 95% CI: 19.5 to 48.0). Conclusion: No change in FIT result across multiple rounds was associated with a low ACN detection rate, while a serial increase was associated with higher ACN detection rates. Further research should consider if sequential rounds of FIT could be used for stratifying individual risk.

Objectives: Colonoscopy surveillance is often performed in post-polypectomy cohorts, likely altering colorectal cancer (CRC) outcomes, but this is often not addressed in CRC incidence analyses. We examined CRC incidence post-endoscopic screening, accounting for surveillance. Methods: We examined UK Flexible Sigmoidoscopy Screening Trial participants who had no, low-risk, or high-risk (≥10 mm, ≥3 adenomas, adenomas with villous features/high-grade dysplasia) distal polyps at screening. Participants with high-risk polyps had an index colonoscopy and 81% had ≥1 surveillance colonoscopies post-screening; <1% of those with no/low-risk polyps had an index or surveillance colonoscopy. We examined CRC incidence over 21 years by anatomic subsite and sex. Standardised incidence ratios (SIRs) compared incidence to general population incidence. Results: Of 39,417 participants, 29,792 (76%), 8162 (21%), and 1463 (4%) had no, low-risk, and high-risk polyps, respectively. In the high-risk group, all-site CRC incidence was non-significantly different from that in the general population, when including all participants, just those who attended surveillance, or just those who did not attend surveillance (SIRs: 0.81 [95% confidence interval: 0.60–1.07]; 0.75 [0.54–1.03]; 1.12 [0.56–2.01], respectively). Without surveillance, compared to the general population, distal cancer incidence was lower among women and men without polyps (SIRs: 0.30 [0.24–0.37]; 0.24 [0.20–0.29], respectively) and women and men with low-risk polyps (SIRs: 0.52 [0.34–0.76]; 0.27 [0.19–0.37], respectively); proximal cancer incidence was lower among men without polyps (SIR: 0.75 [0.64–0.88]), non-significantly different among women without polyps (SIR: 1.07 [0.93–1.22]) and men with low-risk polyps (SIR: 1.22 [0.98–1.51]), but higher among women with low-risk polyps (SIR: 2.22 [1.77–2.76]). Conclusions: Women with low-risk distal polyps at flexible sigmoidoscopy screening had double the risk of proximal colon cancer, compared to the general population.