Menopausal hormone therapy and breast cancer risk: a population-based cohort study of 1.3 million women in Norway.

BACKGROUND: It is important to monitor the association between menopausal hormone therapy (HT) use and breast cancer (BC) risk with contemporary estimates, and specifically focus on HT types and new drugs. METHODS: We estimated hazard ratios (HR) of BC risk according to HT type, administration route and individual drugs, overall and stratified by body mass index (BMI), molecular subtype and detection mode, with non-HT use as reference. RESULTS: We included 1,275,783 women, 45+ years, followed from 2004, for a median of 12.7 years. Oral oestrogen combined with daily progestin was associated with the highest risk of BC (HR 2.42, 95% confidence interval (CI) 2.31-2.54), with drug-specific HRs ranging from Cliovelle®: 1.63 (95% CI 1.35-1.96) to Kliogest®: 2.67 (2.37-3.00). Vaginal oestradiol was not associated with BC risk. HT use was more strongly associated with luminal A cancer (HR 1.97, 95% CI 1.86-2.09) than other molecular subtypes, and more strongly with interval (HR 2.00, 95% CI: 1.83-2.30) than screen-detected (HR 1.33, 95% CI 1.26-1.41) BC in women 50-71 years. HRs for HT use decreased with increasing BMI. CONCLUSIONS: The use of oral and transdermal HT was associated with an increased risk of BC. The associations varied according to HT type, individual drugs, molecular subtype, detection mode and BMI.

Low-Dose Aspirin and Prevention of Colorectal Cancer: Evidence From a Nationwide Registry-Based Cohort in Norway.

INTRODUCTION: To examine the association between low-dose aspirin use and risk of colorectal cancer (CRC). METHODS: In this nationwide cohort study, we identified individuals aged 50 years or older residing for 6 months or more in Norway in 2004-2018 and obtained data from national registers on drug prescriptions, cancer occurrence, and sociodemographic factors. Multivariable Cox regression models were used to estimate the association between low-dose aspirin use and CRC risk. In addition, we calculated the number of CRC potentially averted by low-dose aspirin use. RESULTS: We included 2,186,390 individuals. During the median follow-up of 10.9 years, 579,196 (26.5%) used low-dose aspirin, and 38,577 (1.8%) were diagnosed with CRC. Current use of aspirin vs never use was associated with lower CRC risk (hazard ratio [HR] 0.87, 95% confidence interval [CI] 0.84-0.90). The association was more pronounced for metastatic CRC (HR 0.79; 95% CI 0.74-0.84) than regionally advanced (HR 0.89; 95% CI 0.85-0.92) and localized CRC (HR 0.93; 95% CI 0.87-1.00; P heterogeneity = 0.001). A significant trend was found between duration of current use and CRC risk: HR 0.91 (95% CI 0.86-0.95) for <3 years, HR 0.85 (0.80-0.91) for ≥3 and <5 years, and HR 0.84 (0.80-0.88) for ≥5 years of use vs never use ( P trend < 0.001). For past use, HR were 0.89 (95% CI 0.84-0.94) for <3 years, 0.90 (0.83-0.99) for ≥3 and <5 years, and 0.98 (0.91-1.06) for ≥5 years since last use vs never use ( P -trend < 0.001). We estimated that aspirin use averted 1,073 cases of CRC (95% CI 818-1,338) in the study period. DISCUSSION: In this nationwide cohort, use of low-dose aspirin was associated with a lower risk of CRC.

Lifestyle changes in middle age and risk of cancer: evidence from the European Prospective Investigation into Cancer and Nutrition.

In this study, we aimed to provide novel evidence on the impact of changing lifestyle habits on cancer risk. In the EPIC cohort, 295,865 middle-aged participants returned a lifestyle questionnaire at baseline and during follow-up. At both timepoints, we calculated a healthy lifestyle index (HLI) score based on cigarette smoking, alcohol consumption, body mass index and physical activity. HLI ranged from 0 (most unfavourable) to 16 (most favourable). We estimated the association between HLI change and risk of lifestyle-related cancers-including cancer of the breast, lung, colorectum, stomach, liver, cervix, oesophagus, bladder, and others-using Cox regression models. We reported hazard ratios (HR) with 95% confidence intervals (CI). Median time between the two questionnaires was 5.7 years, median age at follow-up questionnaire was 59 years. After the follow-up questionnaire, we observed 14,933 lifestyle-related cancers over a median follow-up of 7.8 years. Each unit increase in the HLI score was associated with 4% lower risk of lifestyle-related cancers (HR 0.96; 95%CI 0.95-0.97). Among participants in the top HLI third at baseline (HLI > 11), those in the bottom third at follow-up (HLI ≤ 9) had 21% higher risk of lifestyle-related cancers (HR 1.21; 95%CI 1.07-1.37) than those remaining in the top third. Among participants in the bottom HLI third at baseline, those in the top third at follow-up had 25% lower risk of lifestyle-related cancers (HR 0.75; 95%CI 0.65-0.86) than those remaining in the bottom third. These results indicate that lifestyle changes in middle age may have a significant impact on cancer risk.

Lower participation among immigrants in colorectal cancer screening in Norway.

Introduction: Organized cancer screening programs should be equally accessible for all groups in society. We assessed differences in participation in colorectal cancer (CRC) screening among different immigrant groups. Methods: Between 2012 and 2019, 140,000 individuals aged 50 to 74 years were randomly invited to sigmoidoscopy or repeated faecal immunochemical test (FIT) in a CRC screening trial. In this study, we included 46,919 individuals invited to sigmoidoscopy and 70,018 invited to the first round of FIT between 2012 and 2017. We examined difference in participation between non-immigrants and immigrants, and within different immigrant groups by geographic area of origin, using logistic regression models, adjusted for several sociodemographic factors and health factors. Results: In total, we included 106,695 non-immigrants and 10,242 immigrants. The participation rate for FIT was 60% among non-immigrants, 58% among immigrants from Western countries and 37% among immigrants from non-Western countries. The participation rate for sigmoidoscopy was 53% among non-immigrants, 48% among immigrants from Western countries and 23% among immigrants from non-Western countries. Compared to non-immigrants, multivariate adjusted odds ratio for non-participation in FIT screening was 1.13 (95% confidence interval 1.04-1.23) and 1.82 (1.69-1.96) for immigrants from Western and non-Western countries. The corresponding numbers in sigmoidoscopy screening were 1.34 (1.21-1.48) and 2.83 (2.55-3.14). The lowest participation was observed in immigrants from Eastern Europe, Northern Africa and Western Asia, and South-Central Asia. Conclusion: Participation in CRC screening in Norway was particularly low among non-Western immigrants, which could put them at increased risk for late stage diagnosis of CRC. Participation was lower in sigmoidoscopy screening than in FIT screening, especially among immigrants from non-Western countries.

Sentinel Lymph Node Biopsy vs No Axillary Surgery in Patients With Small Breast Cancer and Negative Results on Ultrasonography of Axillary Lymph Nodes: The SOUND Randomized Clinical Trial.

Importance: Sentinel lymph node biopsy (SLNB) is the standard of care for axillary node staging of patients with early breast cancer (BC), but its necessity can be questioned since surgery for examination of axillary nodes is not performed with curative intent. Objective: To determine whether the omission of axillary surgery is noninferior to SLNB in patients with small BC and a negative result on preoperative axillary lymph node ultrasonography. Design, Setting, and Participants: The SOUND (Sentinel Node vs Observation After Axillary Ultra-Sound) trial was a prospective noninferiority phase 3 randomized clinical trial conducted in Italy, Switzerland, Spain, and Chile. A total of 1463 women of any age with BC up to 2 cm and a negative preoperative axillary ultrasonography result were enrolled and randomized between February 6, 2012, and June 30, 2017. Of those, 1405 were included in the intention-to-treat analysis. Data were analyzed from October 10, 2022, to January 13, 2023. Intervention: Eligible patients were randomized on a 1:1 ratio to receive SLNB (SLNB group) or no axillary surgery (no axillary surgery group). Main Outcomes and Measures: The primary end point of the study was distant disease-free survival (DDFS) at 5 years, analyzed as intention to treat. Secondary end points were the cumulative incidence of distant recurrences, the cumulative incidence of axillary recurrences, DFS, overall survival (OS), and the adjuvant treatment recommendations. Results: Among 1405 women (median [IQR] age, 60 [52-68] years) included in the intention-to-treat analysis, 708 were randomized to the SLNB group, and 697 were randomized to the no axillary surgery group. Overall, the median (IQR) tumor size was 1.1 (0.8-1.5) cm, and 1234 patients (87.8%) had estrogen receptor-positive ERBB2 (formerly HER2 or HER2/neu), nonoverexpressing BC. In the SLNB group, 97 patients (13.7%) had positive axillary nodes. The median (IQR) follow-up for disease assessment was 5.7 (5.0-6.8) years in the SLNB group and 5.7 (5.0-6.6) years in the no axillary surgery group. Five-year distant DDFS was 97.7% in the SLNB group and 98.0% in the no axillary surgery group (log-rank P = .67; hazard ratio, 0.84; 90% CI, 0.45-1.54; noninferiority P = .02). A total of 12 (1.7%) locoregional relapses, 13 (1.8%) distant metastases, and 21 (3.0%) deaths were observed in the SLNB group, and 11 (1.6%) locoregional relapses, 14 (2.0%) distant metastases, and 18 (2.6%) deaths were observed in the no axillary surgery group. Conclusions and Relevance: In this randomized clinical trial, omission of axillary surgery was noninferior to SLNB in patients with small BC and a negative result on ultrasonography of the axillary lymph nodes. These results suggest that patients with these features can be safely spared any axillary surgery whenever the lack of pathological information does not affect the postoperative treatment plan. Trial Registration: ClinicalTrials.gov Identifier: NCT02167490.

Using administrative healthcare data to evaluate drug repurposing opportunities for cancer: the possibility of using beta-blockers to treat breast cancer.

Introduction: Cancer registries and hospital electronic medical records are commonly used to investigate drug repurposing candidates for cancer. However, administrative data are often more accessible than data from cancer registries and medical records. Therefore, we evaluated if administrative data could be used to evaluate drug repurposing for cancer by conducting an example study on the association between beta-blocker use and breast cancer mortality. Methods: A retrospective cohort study of women aged ≥50 years with incident breast cancer was conducted using a linked dataset with statewide hospital admission data and nationwide medication claims data. Women receiving beta blockers and first-line anti-hypertensives prior to and at diagnosis were compared. Breast cancer molecular subtypes and metastasis status were inferred by algorithms from commonly prescribed breast cancer antineoplastics and hospitalization diagnosis codes, respectively. Subdistribution hazard ratios (sHR) and corresponding 95% confidence intervals (CIs) for breast cancer mortality were estimated using Fine and Gray's competing risk models adjusted for age, Charlson comorbidity index, congestive heart failure, myocardial infraction, molecular subtype, presence of metastasis at diagnosis, and breast cancer surgery. Results: 2,758 women were hospitalized for incident breast cancer. 604 received beta-blockers and 1,387 received first-line antihypertensives. In total, 154 breast cancer deaths were identified over a median follow-up time of 2.7 years. We found no significant association between use of any beta-blocker and breast-cancer mortality (sHR 0.86, 95%CI 0.58-1.28), or when stratified by beta-blocker type (non-selective, sHR 0.42, 95%CI 0.14-1.25; selective, sHR 0.95, 95%CI 0.63-1.43). Results were not significant when stratified by molecular subtypes (e.g., triple negative breast cancer (TNBC), any beta blocker, sHR 0.16, 95%CI 0.02-1.51). Discussion: It is possible to use administrative data to explore drug repurposing opportunities. Although non-significant, an indication of an association was found for the TNBC subtype, which aligns with previous studies using registry data. Future studies with larger sample size, longer follow-up are required to confirm the association, and linkage to clinical data sources are required to validate our methodologies.

Low-dose aspirin, statins, and metformin and survival in patients with breast cancers: a Norwegian population-based cohort study.

BACKGROUND: Previous studies assessed the prognostic effect of aspirin, statins, and metformin in breast cancer (BC) patients, with inconclusive results. METHODS: We performed a nationwide population-based cohort study to evaluate if post-diagnostic use of low-dose aspirin, statins, and metformin was associated with BC-specific survival. Women aged ≥ 50 years and diagnosed with BC in 2004-2017, who survived ≥ 12 months after diagnosis (follow-up started 12 months after diagnosis), were identified in the Cancer Registry of Norway. The Norwegian Prescription Database provided information on prescriptions. Multivariable Cox proportional hazard models were used to estimate hazard ratios (HR) and 95% confidence intervals (CI) for the association between post-diagnostic use and BC-specific survival, overall and by oestrogen receptor (ER) status. RESULTS: A total of 26,190 patients were included. Of these, 5324 (20%), 7591 (29%), and 1495 (6%) were post-diagnostic users of low-dose aspirin, statins, and metformin, respectively. The median follow-up was 6.1 years, and 2169 (8%) patients died from BC. HRs for use, compared to no use, were estimated at 0.96 (95% CI 0.85-1.08) for low-dose aspirin (ER+: HR = 0.97, 95% CI 0.83-1.13; ER-: HR = 0.97, 95% CI 0.73-1.29, p value for interaction = 0.562), 0.84 (95% CI 0.75-0.94) for statins (ER+: HR = 0.95, 95% CI 0.82-1.09; ER-: HR = 0.77, 95% CI 0.60-1.00, p value for interaction = 0.259), and 0.70 (95% CI 0.51-0.96) for metformin (compared to use of non-metformin antidiabetics) (ER+: HR = 0.67, 95% CI 0.45-1.01; ER-: HR = 1.62, 95% CI 0.72-3.62, p value for interaction = 0.077). CONCLUSION: We found evidence supporting an association between post-diagnostic use of statins and metformin and survival, in patients with BC. Our findings indicate potential differences according to ER status.

Antimuscarinics and lung cancer survival: A Norwegian population-based cohort study.

OBJECTIVES: Epidemiological studies have reported an association between antimuscarinics and reduced risk of cancer, including lung cancer (LC). However, the potential association between antimuscarinic use and LC prognosis has not previously been assessed. In a large population-based cohort, we aimed to investigate the association between the use of antimuscarinics and LC-specific survival. MATERIALS AND METHODS: Norwegian residents, aged ≥ 50 years, and diagnosed with LC between 2005 and 2018, were identified in the Cancer Registry of Norway, and information on filled prescriptions was obtained from the Norwegian Prescription Database. We used Cox proportional hazard models to estimate hazard ratios (HR) and 95 % confidence intervals (CI) for the association between peri-diagnostic and post-diagnostic use of antimuscarinics and LC-specific survival. RESULTS: We included 26,693 patients with incident primary invasive LC. Of these, 466 (1.7 %) were peri-diagnostic users, and 877 (3.3 %) were post-diagnostic users of antimuscarinics, respectively. During a median follow-up of nine months, 18,088 (67.8 %) patients died due to LC. In the overall LC population, the HRs for the association between the use of antimuscarinics, compared to no use, were estimated at 1.01 (95 %CI: 0.90-1.12) for peri-diagnostic use, and 0.84 (95 %CI: 0.77-0.92) for post-diagnostic use. The association with post-diagnostic use was observed in many subgroups defined by sex, age, smoking status, histopathology, and stage, except for patients with unspecified or other histopathology than small cell LC and non-small cell LC, and for patients with local disease. The association was observed in patients treated with chemotherapy (HR = 0.75, 95 %CI: 0.64-0.88), but not in those not treated with chemotherapy (HR = 1.00, 95 %CI: 0.86-1.17; p for interaction: 0.007). CONCLUSION: Our results suggest a possible association between use of antimuscarinics and longer LC-specific survival. More studies are warranted to investigate the use of antimuscarinics to possibly prolong LC prognosis.

Overall lifestyle changes in adulthood are associated with cancer incidence in the Norwegian Women and Cancer Study (NOWAC) - a prospective cohort study.

BACKGROUND: Cancer is a leading cause of premature death worldwide and incidence is expected to rise in the coming decades. Many cohort studies, measuring lifestyle factors at one time-point, have observed that overall healthy lifestyles were inversely related to cancer incidence. However, there is little knowledge on the impact of lifestyle modification within adulthood. METHODS: Using the Norwegian Women and Cancer study, two repeated self-reported assessments of lifestyle behaviours were used to calculate healthy lifestyle index scores at each time-point (N = 66 233). The associations between change in healthy lifestyle index score and lifestyle-related cancer incidence, including alcohol-, tobacco-, obesity-, and reproductive-related, and site-specific breast and colorectal cancer incidence were estimated using Cox proportional hazard regression models. To assess nonlinearity in the dose-response relationships, restricted cubic spline models were used. RESULTS: Independent of baseline lifestyle, positive lifestyle changes were inversely related to the incidence of overall lifestyle-related cancers, as well as alcohol-related, tobacco-related, obesity-related, and reproductive-related cancers, but not breast and colorectal site-specific cancers. An association between lifestyle worsening and cancer incidence compared to stable lifestyle was observed. CONCLUSIONS: This study provides evidence that overall lifestyle changes among cancer-free women between the ages of 41 and 76 impact the incidence of many cancer types. Regardless of baseline lifestyle, there was a negative dose-response relationship between magnitude of positive lifestyle change and the incidence of overall lifestyle-related cancers. We observed that underlying this trend was an especially clear association between lifestyle worsening and increased risk compared to stable lifestyle. For adult women, maintaining a stable healthy lifestyle and lifestyle improvement are important for preventing the occurrence of many cancer types.

Beta-blockade enhances anthracycline control of metastasis in triple-negative breast cancer.

Beta-adrenergic blockade has been associated with improved cancer survival in patients with triple-negative breast cancer (TNBC), but the mechanisms of these effects remain unclear. In clinical epidemiological analyses, we identified a relationship between beta-blocker use and anthracycline chemotherapy in protecting against TNBC progression, disease recurrence, and mortality. We recapitulated the effect of beta-blockade on anthracycline efficacy in xenograft mouse models of TNBC. In metastatic 4T1.2 and MDA-MB-231 mouse models of TNBC, beta-blockade improved the efficacy of the anthracycline doxorubicin by reducing metastatic development. We found that anthracycline chemotherapy alone, in the absence of beta-blockade, increased sympathetic nerve fiber activity and norepinephrine concentration in mammary tumors through the induction of nerve growth factor (NGF) by tumor cells. Moreover, using preclinical models and clinical samples, we found that anthracycline chemotherapy up-regulated ß2-adrenoceptor expression and amplified receptor signaling in tumor cells. Neurotoxin inhibition of sympathetic neural signaling in mammary tumors using 6-hydroxydopamine or genetic deletion of NGF or ß2-adrenoceptor in tumor cells enhanced the therapeutic effect of anthracycline chemotherapy by reducing metastasis in xenograft mouse models. These findings reveal a neuromodulatory effect of anthracycline chemotherapy that undermines its potential therapeutic impact, which can be overcome by inhibiting ß2-adrenergic signaling in the tumor microenvironment. Supplementing anthracycline chemotherapy with adjunctive ß2-adrenergic antagonists represents a potential therapeutic strategy for enhancing the clinical management of TNBC.

Low-dose aspirin and risk of breast cancer: a Norwegian population-based cohort study of one million women.

Several studies evaluated the association between aspirin use and risk of breast cancer (BC), with inconsistent results. We identified women aged ≥ 50 years residing in Norway between 2004 and 2018, and linked data from nationwide registries; including the Cancer Registry of Norway, the Norwegian Prescription Database, and national health surveys. We used Cox regression models to estimate the association between low-dose aspirin use and BC risk, overall and by BC characteristics, women's age and body mass index (BMI), adjusting for sociodemographic factors and use of other medications. We included 1,083,629 women. During a median follow-up of 11.6 years, 257,442 (24%) women used aspirin, and 29,533 (3%) BCs occurred. For current use of aspirin, compared to never use, we found an indication of a reduced risk of oestrogen receptor-positive (ER +) BC (hazard ratio [HR] = 0.96, 95% confidence interval [CI]: 0.92-1.00), but not ER-negative BC (HR = 1.01, 95%CI: 0.90-1.13). The association with ER + BC was only found in women aged ≥ 65 years (HR = 0.95, 95%CI: 0.90-0.99), and became stronger as the duration of use increased (use of ≥ 4 years HR = 0.91, 95%CI: 0.85-0.98). BMI was available for 450,080 (42%) women. Current use of aspirin was associated with a reduced risk of ER + BC in women with BMI ≥ 25 (HR = 0.91, 95%CI: 0.83-0.99; HR = 0.86, 95%CI: 0.75-0.97 for use of ≥ 4 years), but not in women with BMI < 25.Use of low-dose aspirin was associated with reduced risk of ER + BC, in particular in women aged ≥ 65 years and overweight women.

Association between use of low-dose aspirin and detection of colorectal polyps and cancer in a screening setting.

BACKGROUND: The possible protective effect of aspirin on risk of colorectal cancer (CRC) is still highly debated. METHODS: We used data from Bowel Cancer Screening in Norway, a trial randomizing individuals from general population, aged 50-74 years, to flexible sigmoidoscopy or faecal immunochemical test (FIT), to study the association between aspirin use and detection of CRC and two CRC precursors: adenomas and advanced serrated lesions (ASL). Prescriptions of low-dose aspirin were obtained from Norwegian prescription database. Logistic regression was used to estimate odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: Among 64,889 screening participants (24,159 sigmoidoscopy, 40,730 FIT), 314 (0.5%) had CRC, 6,208 (9.6%) adenoma and 659 (1.0%) ASL. Overall and short-term use (<3 years) of low-dose aspirin, versus no use, were not associated with any colorectal lesion. Long-term use (≥3 years) was associated with lower detection of CRC (overall OR 0.66, 95%CI 0.46-0.93; sigmoidoscopy: 0.56, 0.33-0.97; FIT: 0.72, 0.45-1.15), adenomas in sigmoidoscopy arm (overall OR 0.95, 95%CI 0.87-1.03; sigmoidoscopy: 0.89, 0.80-0.99; FIT: 1.03, 0.89-1.18), but not ASLs. We did not observe significant differences in the effect of aspirin according to the location of colorectal lesions. CONCLUSION: Our results suggest that long-term use of aspirin might have a protective effect against adenomas and colorectal cancer, but not ASLs.

Colonoscopy quality improvement after initial training: A cross-sectional study of intensive short-term training.

Background and study aims High-quality is crucial for the effectiveness of colonoscopy and can be achieved by high-quality training and verified with assessment of key performance indicators (KPIs) for colonoscopy such as cecum intubation rate (CIR), adenoma detection rate (ADR) and adequate polyp resection. Typically, trainees achieve adequate CIR after 275 procedures, but little is known about learning curves for KPIs after initial training. Methods This cross-sectional study includes work-up colonoscopies after a positive screening test with fecal occult blood testing (FIT) or sigmoidoscopy, performed by either trainees after 300 training colonoscopies or by consultants. Outcome measures were KPIs. We assessed inter-endoscopist variation in trainees and learning curves for trainees as a group. We also compared KPIs for trainees and consultants as a group.  Results Data from 6,655 colonoscopies performed by 21 trainees and 921 colonoscopies performed by 17 consultants were included. Most trainees achieved target standards for main KPIs. With time, trainees shortened cecum intubation time and withdrawal time without decreasing their ADR, reduced the proportion of painful colonoscopies, and increased the adequate polyp resection rate (all P  < 0.01). Compared to consultants, trainees had higher CIR (97.7 % vs. 96.3 %, P  = 0.02), ADR after positive FIT (57.6 % vs. 50.3 %, P  < 0.01), and proximal ADR after sigmoidoscopy screening (41.1 % vs. 29.8 %; P  < 0.01), higher adequate polyp resection rate (94.9 % vs. 93.1 %, P  = 0.01) and fewer serious adverse events (0.65 % vs. 1.41 %, P  = 0.02). Conclusions Trainees performed high-quality colonoscopies and achieved international target standards. Several KPIs continuously improved after initial training. Trainees outperformed consultants on several KPIs.

Type and Severity of Mental Illness and Participation in Colorectal Cancer Screening.

INTRODUCTION: The effectiveness of colorectal cancer screening programs depends on the participation rate. This study examined the association between type and severity of mental illness and colorectal cancer screening participation. METHODS: Between 2012 and 2017, a total of 46,919 individuals were invited to sigmoidoscopy screening in Norway, and 70,019 were invited to fecal immunochemical testing. In 2022, logistic regression was used to evaluate the association between the use of antipsychotics, anxiolytics, hypnotics, and antidepressants in the year preceding the screening invitation and screening participation, adjusted for demographic and socioeconomic factors. Defined daily doses of individual drugs were used to assess dose‒response relationships. RESULTS: Overall, 19.2% (24.8% of women, 13.4% of men) of all invitees used at least 1 psychotropic medication. Nonparticipation in the 2 arms combined was associated with the use of anxiolytics (60.7% in users vs 43.2% in nonusers; OR=1.53; 95% CI=1.45, 1.62) and antipsychotics (64.3% vs 43.8%; OR=1.41; 95% CI=1.30, 1.53) and increased with higher doses for both drugs. Hypnotics and antidepressants were only weakly associated with nonparticipation in higher doses. Participation rates were 57.3%, 52.3%, 42.9%, and 35.4% in those prescribed 0, 1, 2, and 3-4 classes of psychotropic medications, respectively. The associations between the use of psychotropic medications and nonparticipation were similar for the 2 screening tests. CONCLUSIONS: These findings show significant disparities in colorectal cancer screening participation for individuals with mental illness, independent of the screening method. Moreover, screening participation varied depending on the type and severity of mental illness. Targeted interventions are warranted to ensure that people with mental illness are supported to access the benefits of colorectal cancer screening.

Changes in Lifestyle and Risk of Colorectal Cancer in the European Prospective Investigation Into Cancer and Nutrition.

INTRODUCTION: We investigated the impact of changes in lifestyle habits on colorectal cancer (CRC) risk in a multicountry European cohort. METHODS: We used baseline and follow-up questionnaire data from the European Prospective Investigation into Cancer cohort to assess changes in lifestyle habits and their associations with CRC development. We calculated a healthy lifestyle index (HLI) score based on smoking status, alcohol consumption, body mass index, and physical activity collected at the 2 time points. HLI ranged from 0 (most unfavorable) to 16 (most favorable). We estimated the association between HLI changes and CRC risk using Cox regression models and reported hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: Among 295,865 participants, 2,799 CRC cases were observed over a median of 7.8 years. The median time between questionnaires was 5.7 years. Each unit increase in HLI from the baseline to the follow-up assessment was associated with a statistically significant 3% lower CRC risk. Among participants in the top tertile at baseline (HLI > 11), those in the bottom tertile at follow-up (HLI ≤ 9) had a higher CRC risk (HR 1.34; 95% CI 1.02-1.75) than those remaining in the top tertile. Among individuals in the bottom tertile at baseline, those in the top tertile at follow-up had a lower risk (HR 0.77; 95% CI 0.59-1.00) than those remaining in the bottom tertile. DISCUSSION: Improving adherence to a healthy lifestyle was inversely associated with CRC risk, while worsening adherence was positively associated with CRC risk. These results justify and support recommendations for healthy lifestyle changes and healthy lifestyle maintenance for CRC prevention.

Impact of time between faecal immunochemical tests in colorectal cancer screening on screening results: A natural experiment.

Repeated rounds of faecal immunochemical testing (FIT) for occult blood is a common method for screening for colorectal cancer (CRC). However, the time interval between FIT rounds is not thoroughly investigated. In a CRC screening trial in South-Eastern Norway, individuals were invited for biennial FIT between 2012 and 2019. The positivity threshold was >15 mcg haemoglobin/g faeces (mcg/g). Due to organizational challenges, the interval between screening rounds randomly varied between 1.5 and 3.5 years, forming a natural experiment. We investigated the detection rate of CRC and advanced neoplasia (AN: CRC or advanced adenoma) at the subsequent round (FIT2 ), according to the faecal haemoglobin concentration (f-Hb) at the initial screening round (FIT1 ), and time between the two screening rounds. 18 522 individuals with negative FIT1 who attended FIT2 were included in this study. 245 AN were detected at FIT2 , of which 34 were CRC. The CRC detection rate at FIT2 for participants with FIT1  = 0 mcg/g was 0.09% while it was 0.28% for participant with 0 > FIT1 ≤ 15 mcg/g; odds ratio (OR) 3.22, 95% CI 1.49-6.95. For each 3 months' increment between FITs, the OR for detecting CRC was 1.33 (95% CI 0.98-1.79), while the OR was 1.13 (1.02-1.26) for AN. Individuals with FIT1 -value of 0 mcg/g, had a lower AN detection rate compared with participants with 0 > FIT1 ≤ 15 mcg/g, irrespective of time between tests. Although CRC and AN detection rates increase with increasing time interval between FITs, individuals with undetectable f-Hb at first screen have substantially lower risk of CRC at the next screening round compared with individuals with detectable f-Hb.

Baseline and lifetime alcohol consumption and risk of skin cancer in the European Prospective Investigation into Cancer and Nutrition cohort (EPIC).

Experimental evidence suggests that alcohol induces cutaneous carcinogenesis, yet epidemiological studies on the link between alcohol intake and skin cancer have been inconsistent. The European Prospective Investigation into Cancer and Nutrition (EPIC) is a prospective cohort initiated in 1992 in 10 European countries. Alcohol intake at baseline and average lifetime alcohol intake were assessed using validated country-specific dietary and lifestyle questionnaires. Hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated in Cox models. A total of 14 037 skin cancer cases (melanoma: n = 2457; basal-cell carcinoma (BCC): n = 8711; squamous-cell carcinoma (SCC): n = 1928; unknown: n = 941) were identified among 450 112 participants (average follow-up: 15 years). Baseline alcohol intake was positively associated with SCC (>15 vs 0.1-4.9 g/day: HR = 1.44, 95% CI = 1.17-1.77; Ptrend  = .001), BCC (HR = 1.12, 95% CI = 1.01-1.23; Ptrend  = .04), and melanoma risks in men (HR = 1.17, 95% CI = 0.95-1.44; Ptrend  = .17), while associations were more modest in women (SCC: HR = 1.09, 95% CI = 0.90-1.30; Ptrend  = .13; BCC: HR = 1.08, 95% CI = 1.00-1.17, Ptrend  = .03; melanoma: HR = 0.93, 95% CI = 0.80-1.08, Ptrend  = .13). Associations were similar for lifetime alcohol intake, with an attenuated linear trend. Lifetime liquor/spirit intake was positively associated with melanoma (fourth vs first quartile: HR = 1.47, 95% CI = 1.08-1.99; Ptrend  = .0009) and BCC risks in men (HR = 1.17, 95% CI = 1.04-1.31; Ptrend  = .14). Baseline and lifetime intakes of wine were associated with BCC risk (HR = 1.25 in men; HR = 1.11-1.12; in women). No statistically significant associations were found between beverage types and SCC risk. Intake of beer was not associated with skin cancer risk. Our study suggests positive relationships between alcohol intake and skin cancer risk, which may have important implications for the primary prevention of skin cancer.

The impact of driving time on participation in colorectal cancer screening with sigmoidoscopy and faecal immunochemical blood test.

BACKGROUND: High participation rates are important for a colorectal cancer (CRC) screening programme to be effective. Having a long travelling distance to screening centres may impede participation. METHODS: We analysed the association between driving time from home address to screening centre and participation among individuals invited to screening with faecal immunochemical test (FIT) (n = 68,624) or sigmoidoscopy (n = 46,076) in a randomized trial in Norway in 2012-17. Two screening centres were involved. We fitted multiple logistic regression models, adjusted for demographic, socioeconomic and health characteristics, and reported odds ratios (OR) with 95% confidence intervals (CI). RESULTS: Participation rates were 58.9 % (n = 40,445) for FIT and 51.9 % (n = 23,911) for sigmoidoscopy. In sigmoidoscopy, participation was 56.9 % and 47.9 % in those living < 20 and > 60 min by car from the screening centres, respectively. For each 10 min driving time increase, OR for participating in sigmoidoscopy screening was 0.93 (95 % CI 0.91-0.95). There was a significant difference between the two screening centres (p-value for heterogeneity <0.001). Participation in FIT screening were 61.2 % and 57.1 % in those with < 20 and > 60 min driving time, respectively, and the OR was 0.98 (95 % CI 0.96-0.99) for each 10 min increase (heterogeneity between screening methods, P-value <0.001). Among those with a positive FIT, compliance to colonoscopy was higher in those living < 20 compared to > 60 min from the centres (95.1 % vs. 92.9 %, respectively, OR 0.86; 95 % CI 0.77-0.93 for each 10 min increase). CONCLUSIONS: Driving time to screening centre was a significant predictor of participation, mainly in sigmoidoscopy. There were local differences in the impact of driving time on participation. Driving time also affected compliance to colonoscopy after a positive FIT. When planning a CRC screening programme, one should consider offering people living far from screening sites special assistance to facilitate their participation.