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 identifed 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 receptorpositive (ER+) BC (hazard ratio [HR]=0.96, 95% confdence 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

Impact of the Mobile Game FightHPV on Cervical Cancer Screening Attendance: Retrospective Cohort Study

Background: The wide availability of mobile phones has made it easy to disseminate health-related information and make it accessible. With gamification, mobile apps can nudge people to make informed health choices, including attending cervical cancer screening. Objective: This matched retrospective cohort study examined the association between exposure to the FightHPV mobile app gamified educational content and having a cervical exam in the following year. Methods: Women aged 20 to 69 years who signed an electronic consent form after downloading the FightHPV app in 2017 (intervention group) were matched 1:6 with women of the same age and with the same screening history (reference group) in 2015. To estimate the impact of exposure to the FightHPV app, we estimated cumulative incidence and hazard ratios (HRs) with 95% CIs. We used data from the Norwegian Cervical Cancer Screening Program database and Statistics Norway to determine screening participation and outcomes, respectively. Results: We matched 3860 women in the control group to 658 women in the intervention group; 6 months after enrollment, 29.6% (195/658) of the women in the intervention group and 15.21% (587/3860) of those in the reference group underwent a cervical exam (P<.01). Women exposed to the FightHPV app were 2 times more likely to attend screening (adjusted HR 2.3, 95% CI 2.0-2.7), during which they were 13 times more likely to be diagnosed with high-grade abnormality (adjusted HR 12.7, 95% CI 5.0-32.5) than the women in the reference group. Conclusions: Exposure to the FightHPV app significantly increased cervical cancer screening attendance across the various analyses and improved detection of women with high risk for cervical cancer. For the first time, we demonstrated the effectiveness of gamification combined with mobile technology in cancer prevention by empowering women to make active health-related decisions. Gamification can significantly improve the understanding of complicated scientific concepts behind interventions and increase the acceptance of proposed cancer control measures.publishedVersio

HPV testing for cervical cancer in Romania: High-risk HPV prevalence among ethnic subpopulations and regions

Background: Romania has had one of the highest rates of cervical cancer incidence and mortality in Europe for decades. Data on the high-risk human papillomavirus (hrHPV) prevalence within the Romanian population are crucial for cervical cancer intervention in high risk groups. The aim of this study was to determine the prevalence of hrHPV infection in Romania, identifying high-risk areas for cervical cancer prevention efforts. Methods: The target population of this study were women of all forms in Romania, including ethnic minorities, women from urban and rural areas, and women in various regions. Women with no history of precancerous or cancerous lesions were offered hrHPV screening. The specimens were tested with Hybrid Capture 2 (HC2) DNA test. Age-standardized hrHPV prevalence rates with 95% confidence intervals (CI) were estimated. Results: hrHPV results of 2060 women aged 18 to 70 years were analyzed. The highest hrHPV prevalence rates were observed among: Romanians (17.9%; 95 CI: 15.5–20.7%), Hungarians (16.6%; 95% CI: 13.1–20.8%), Russians (15.6%; 95% CI: 11.3–21.3%), women living in North (19.2%; 95% CI: 16.5–22.3%), and West regions (23.0%; 95 CI: 18.6–28.0%), and women living in urban areas (20.0%; 95 CI: 18.5–28.0%). hrHPV prevalence rates were lower for the Roma population (7.8%; 95% CI: 4.7–12.5%). Conclusions: These hrHPV prevalence rates in a high cervical cancer incidence country provide baseline information for targeted cervical cancer intervention strategies as well as a baseline to measure the impact of hrHPV vaccination in the future

Drug Use and Cancer Risk: A Drug-Wide Association Study (DWAS) in Norway

Background: Population-based pharmaco-epidemiologic studies are used to assess postmarketing drug safety and discover beneficial effects of off-label drug use. We conducted a drug-wide association study (DWAS) to screen for associations between prescription drugs and cancer risk. Methods: This registry-based, nested case–control study, 1:10 matched on age, sex, and date of diagnosis of cases, comprises approximately 2 million Norwegian residents, including their drug history from 2004 to 2014. We evaluated the association between prescribed drugs, categorized according to the anatomical therapeutic chemical (ATC) classification system, and the risk of the 15 most common cancer types, overall and by histology. We used stratified Cox regression, adjusted for other drug use, comorbidity, county, and parity, and explored dose–response trends. Results: We found 145 associations among 1,230 drug–cancer combinations on the ATC2-level and 77 of 8,130 on the ATC4-level. Results for all drug–cancer combinations are presented in this article and an online tool (https://pharmacoepi.shinyapps.io/drugwas/). Some associations have been previously reported, that is, menopausal hormones and breast cancer risk, or are likely confounded, that is, chronic obstructive pulmonary diseases and lung cancer risk. Other associations were novel, that is, inverse association between proton pump inhibitors and melanoma risk, and carcinogenic association of propulsives and lung cancer risk. Conclusions: This study confirmed previously reported associations and generated new hypotheses on possible carcinogenic or chemopreventive effects of prescription drugs. Results from this type of explorative approach need to be validated in tailored epidemiologic and preclinical studies. Impact: DWAS studies are robust and important tools to define new drug–cancer hypotheses

Drug Use and Cancer Risk: A Drug-Wide Association Study (DWAS) in Norway*

Background: Population-based pharmaco-epidemiologic studies are used to assess postmarketing drug safety and discover beneficial effects of off-label drug use. We conducted a drug-wide association study (DWAS) to screen for associations between prescription drugs and cancer risk. Methods: This registry-based, nested case–control study, 1:10 matched on age, sex, and date of diagnosis of cases, comprises approximately 2 million Norwegian residents, including their drug history from 2004 to 2014. We evaluated the association between prescribed drugs, categorized according to the anatomical therapeutic chemical (ATC) classification system, and the risk of the 15 most common cancer types, overall and by histology. We used stratified Cox regression, adjusted for other drug use, comorbidity, county, and parity, and explored dose–response trends. Results: We found 145 associations among 1,230 drug–cancer combinations on the ATC2-level and 77 of 8,130 on the ATC4-level. Results for all drug–cancer combinations are presented in this article and an online tool (https://pharmacoepi.shinyapps.io/drugwas/). Some associations have been previously reported, that is, menopausal hormones and breast cancer risk, or are likely confounded, that is, chronic obstructive pulmonary diseases and lung cancer risk. Other associations were novel, that is, inverse association between proton pump inhibitors and melanoma risk, and carcinogenic association of propulsives and lung cancer risk. Conclusions: This study confirmed previously reported associations and generated new hypotheses on possible carcinogenic or chemopreventive effects of prescription drugs. Results from this type of explorative approach need to be validated in tailored epidemiologic and preclinical studies. Impact: DWAS studies are robust and important tools to define new drug–cancer hypotheses

Menopausal hormone therapy and colorectal cancer: a linkage between nationwide registries in Norway.

Objectives: With the present study, we aimed to investigate the association between menopausal hormone therapy (HT) and risk of colorectal cancer (CRC). Setting: Cohort study based on the linkage of Norwegian population-based registries. Participants: We selected 466822 Norwegian women, aged 55–79, alive and residing in Norway as of 1 January 2004, and we followed them from 2004 to 2008. Each woman contributed person-years at risk as non-user, current user and/or past HT user. Outcome measures: The outcome of interest was adenocarcinoma of the colorectal tract, overall, by anatomic site and stage at diagnosis. Incidence rate ratios (RRs) with 95%CIs were estimated by Poisson regression and were used to evaluate the association between HT and CRC incidence. Results: During the median follow-up of 4.8 years, 138 655 (30%) women received HT and 3799 (0.8%) incident CRCs occurred. Current, but not past, use of HT was associated with a lower risk of CRC (RR 0.88; 95% CI 0.80 to 0.98). RRs for localised, regionally advanced and metastatic CRC were 1.13 (95% CI 0.91 to 1.41), 0.81 (95% CI 0.70 to 0.94) and 0.79 (95% CI 0.62 to 1.00), respectively. RRs for current use of oestrogen therapy (ET) were 0.91 (95%CI 0.80 to 1.04) while RR for current use of combined oestrogen–progestin therapy (EPT) was 0.85 (95% CI 0.70 to 1.03), as compared with no use of HT. The same figures for ET and EPT in oral formulations were 0.83 (95% CI 0.68 to 1.03) and 0.86 (95% CI 0.71 to 1.05), respectively. Conclusions: In our nationwide cohort study, HT use lowered the risk of CRC, specifically the most advanced CRC

Menopausal hormone therapy and colorectal cancer: a linkage between nationwide registries in Norway.

Objectives: With the present study, we aimed to investigate the association between menopausal hormone therapy (HT) and risk of colorectal cancer (CRC). Setting: Cohort study based on the linkage of Norwegian population-based registries. Participants: We selected 466822 Norwegian women, aged 55–79, alive and residing in Norway as of 1 January 2004, and we followed them from 2004 to 2008. Each woman contributed person-years at risk as non-user, current user and/or past HT user. Outcome measures: The outcome of interest was adenocarcinoma of the colorectal tract, overall, by anatomic site and stage at diagnosis. Incidence rate ratios (RRs) with 95% CIs were estimated by Poisson regression and were used to evaluate the association between HT and CRC incidence. Results: During the median follow-up of 4.8 years, 138 655 (30%) women received HT and 3799 (0.8%) incident CRCs occurred. Current, but not past, use of HT was associated with a lower risk of CRC (RR 0.88; 95% CI 0.80 to 0.98). RRs for localised, regionally advanced and metastatic CRC were 1.13 (95% CI 0.91 to 1.41), 0.81 (95% CI 0.70 to 0.94) and 0.79 (95% CI 0.62 to 1.00), respectively. RRs for current use of oestrogen therapy (ET) were 0.91 (95% CI 0.80 to 1.04) while RR for current use of combined oestrogen–progestin therapy (EPT) was 0.85 (95% CI 0.70 to 1.03), as compared with no use of HT. The same figures for ET and EPT in oral formulations were 0.83 (95% CI 0.68 to 1.03) and 0.86 (95% CI 0.71 to 1.05), respectively. Conclusions: In our nationwide cohort study, HT use lowered the risk of CRC, specifically the most advanced CRC

Anthropometric factors and Breslow thickness: prospective data on 2570 cases of cutaneous melanoma in the population-based Janus Cohort

Background Breslow thickness is the most important prognostic factor of localized cutaneous melanoma (CM), but associations with anthropometric factors have been sparsely and incompletely investigated. Objectives To examine prediagnostic body mass index (BMI), body surface area (BSA), and height, weight and weight change in relation to Breslow thickness, overall and by anatomical site and histological subtype; and to assess possible nonlinear associations between these anthropometric factors and Breslow thickness. Methods CMs in the Janus Cohort were identified between 1972 and 2014. Linear regression was used to estimate geometric mean ratios (GMRs) of Breslow thickness with 95% confidence intervals (CIs) according to anthropometric factors. Restricted cubic splines in generalized linear models predicted adjusted mean Breslow thickness, and were used to assess possible nonlinear relationships. Results Of 2570 cases of CM, obese patients had a GMR of 1·16 (95% CI 1·04–1·30) of Breslow thickness vs. normal‐weight patients. For BSA and weight, quintile 5 showed GMRs of 1·13 (95% CI 1·00–1·27) and 1·17 (95% CI 1·03–1·33) of Breslow thickness vs. quintile 1, respectively. Associations seemed restricted to superficial spreading melanomas and CMs on the trunk and lower limbs. The associations plateaued at an adjusted mean Breslow thickness of about 2·5 mm (BMI 29 kg m−2, BSA 2·05 m2 and weight 90 kg), before declining for the highest values. No associations were found for height and weight change. Conclusions This large case‐series of incident CM demonstrated positive associations between BMI, BSA, weight and Breslow thickness, and suggested that behavioural or other mechanisms apply at high values. This is the peer reviewed version of the article, which has been published in final form at Wiley. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.

Prediagnostic serum 25-hydroxyvitamin D and melanoma risk

Abstract Previous studies of serum 25-hydroxyvitamin D (25(OH)D) in relation to melanoma have shown conflicting results. We conducted a nested case–control study of 708 cases and 708 controls, using prediagnostically collected serum, to study 25(OH)D and melanoma risk in the population-based Janus Serum Bank Cohort. Stratified Cox regression was used to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) adjusted for ultraviolet radiation (UVR) indicators and stratified by ambient UVB of residence and body mass index (BMI). Non-linear associations were studied by restricted cubic splines. Missing data were handled with multiple imputation by chained equations. We found an HR of melanoma risk of 1.01 (95% CI: 0.99, 1.04) and an HR imputed of 1.02 (95% CI: 1.00, 1.04) per 5-nmol/L increase. The spline model showed exposure-risk curves with significantly reduced melanoma risk between 60 and 85 nmol/L 25(OH)D (reference 50 nmol/L). Non-significant J-shaped curves were found in sub-analyses of subjects with high ambient UVB of residence and of subjects with BMI &lt; 25 kg/m 2 . Our data did not yield persuasive evidence for an association between 25(OH)D and melanoma risk overall. Serum levels within the medium range might be associated with reduced risk, an association possibly mediated by BMI