Publications by authors named "Hans-Olov Adami"

442 Publications

A comprehensive risk score for effective risk stratification and screening of nasopharyngeal carcinoma.

Nat Commun 2021 08 31;12(1):5189. Epub 2021 Aug 31.

State Key Laboratory of Oncology in South China, Collaborative Innovation Center for Cancer Medicine, Guangdong Key Laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy, Sun Yat-sen University Cancer Center, Guangzhou, P. R. China.

Using Epstein-Barr virus (EBV)-based markers to screen populations at high risk for nasopharyngeal carcinoma (NPC) is an attractive preventive approach. Here, we develop a comprehensive risk score (CRS) that combines risk effects of EBV and human genetics for NPC risk stratification and validate this CRS within an independent, population-based dataset. Comparing the top decile with the bottom quintile of CRSs, the odds ratio of developing NPC is 21 (95% confidence interval: 12-37) in the validation dataset. When combining the top quintile of CRS with EBV serology tests currently used for NPC screening in southern China, the positive prediction value of screening increases from 4.70% (serology test alone) to 43.24% (CRS plus serology test). By identifying individuals at a monogenic level of NPC risk, this CRS approach provides opportunities for personalized risk prediction and population screening in endemic areas for the early diagnosis and secondary prevention of NPC.
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http://dx.doi.org/10.1038/s41467-021-25402-zDOI Listing
August 2021

Cancer outcomes research-a European challenge: measures of the cancer burden.

Mol Oncol 2021 May 18. Epub 2021 May 18.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.

In a mission that aims to improve cancer control throughout Europe, the European Academy of Cancer Sciences has defined two key indicators of progress: within one to two decades, overall cancer-specific 10-year survival should reach 75%, and in each country, overall cancer mortality rates should be convincingly declining. To lay the ground for assessment of progress and to promote cancer outcomes research in general, we have reviewed the most common population-based measures of the cancer burden. We emphasize the complexities and complementary approaches to measure cancer survival and the novel opportunities for improved assessment of quality of life. We propose that: incidence and mortality rates are standardized to the European population; net survival is used as the measure of prognosis but with proper adjustments for confounding when temporal trends in overall cancer survival are assessed; and cancer-specific quality of life is measured by a combination of existing questionnaires and utilizes emerging communication technologies. We conclude that all measures are important and that a meaningful interpretation also requires a deep understanding of the larger clinical and public health context.
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http://dx.doi.org/10.1002/1878-0261.13012DOI Listing
May 2021

Dietary patterns and risk of nasopharyngeal carcinoma: a population-based case-control study in southern China.

Am J Clin Nutr 2021 08;114(2):462-471

Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.

Background: Dietary factors, such as consumption of preserved foods, fresh vegetables, and fruits, have been linked to the risk of nasopharyngeal carcinoma (NPC). However, little is known about associations between dietary patterns and the risk of NPC in NPC-endemic areas.

Objectives: We aimed to evaluate whether dietary patterns are associated with NPC risk.

Methods: We studied 2554 newly diagnosed NPC patients aged 20-74 y living in 3 endemic regions of southern China, and 2648 population-based controls frequency-matched to case patients by age, sex, and region, between 2010 and 2014. Dietary components were derived from food frequency data in adulthood and adolescence using principal component analysis. Four dietary components were identified and highly similar in adulthood and adolescence. We used multivariable unconditional logistic regression to calculate ORs with 95% CIs for the association between dietary patterns and NPC risk.

Results: Compared with the lowest quartile, individuals in the highest quartile of the "plant-based factor" in adulthood had a 52% (OR: 0.48; 95% CI: 0.38, 0.59) decreased risk of NPC, and those in the highest quartile of the "animal-based factor" had a >2-fold (OR: 2.26; 95% CI: 1.85, 2.77) increased risk, with a monotonic dose-response trend (P-trend < 0.0001). Similar but weaker associations were found in adolescence. High intakes of the "preserved-food factor" were associated with increased NPC risk in both periods, although stronger associations were found in adolescence. Results from joint analysis and sensitivity analyses indicated that dietary factors in adulthood might be more stable and robust predictors of NPC risk than those in adolescence.

Conclusions: Our results deliver compelling evidence that plant- and animal-based dietary factors are associated with NPC risk, and provide more insights on the associations of diets and cancer risk that may assist healthy diet recommendations.
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http://dx.doi.org/10.1093/ajcn/nqab114DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8326029PMC
August 2021

The Evolving Epidemiology of Nasopharyngeal Carcinoma.

Cancer Epidemiol Biomarkers Prev 2021 06 13;30(6):1035-1047. Epub 2021 Apr 13.

Department of Epidemiology, Harvard T.H. Chan School of Public Health, Boston, Massachusetts.

Background: The epidemiology of nasopharyngeal carcinoma (NPC) has long been a source of fascination due to the malignancy's striking geographic distribution, the involvement of the oncogenic Epstein-Barr virus (EBV), the unique association with intake of Chinese-style salt-preserved fish, and etiologic heterogeneity by histologic subtype.

Methods: This review summarizes the current epidemiologic literature on NPC, highlighting recent results from our population-based case-control study in southern China.

Results: Findings from our case-control study provide new insight into the epidemiology of NPC, including a diminished role of Chinese-style salt-preserved fish, a profound impact of EBV genetic sequence variation, modest positive associations with passive smoking and household air pollution, and possible effects of oral health and the oral microbiome. Recent findings from other studies include a protective association with infectious mononucleosis, suggesting a causal role of early EBV infection; familial risk conferred by shared genetic variation in the host antibody-mediated immune response to EBV infection; and an unclear association with occupational exposure to formaldehyde.

Conclusions: To shed further light on the interplay of environmental, genetic, and viral causes of NPC, large pooled studies must accumulate sufficient cases with detailed exposure data.

Impact: New epidemiologic findings have reshaped the causal model for NPC.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1702DOI Listing
June 2021

Occupational exposures and risk of nasopharyngeal carcinoma in a high-risk area: A population-based case-control study.

Cancer 2021 Aug 6;127(15):2724-2735. Epub 2021 Apr 6.

Department of Medical Epidemiology and Biostatistics, Karolinska Institute, Stockholm, Sweden.

Background: The potential role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas.

Methods: The authors conducted a population-based case-control study, consisting of 2514 incident NPC cases and 2586 randomly selected population controls, in southern China from 2010 to 2014. Occupational history and other covariates were self-reported using a questionnaire. Multivariate logistic regression was used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with occupational exposures. Restricted cubic splines were used to evaluate potentially nonlinear duration-response relations.

Results: Individuals who had exposure to occupational dusts (OR, 1.45; 95% CI, 1.26-1.68), chemical vapors (OR, 1.37; 95% CI, 1.17-1.61), exhausts/smokes (OR, 1.42; 95% CI, 1.25-1.60), or acids/alkalis (OR, 1.56; 95% CI, 1.30-1.89) in the workplace had an increased NPC risk compared with those who were unexposed. Risk estimates for all 4 categories of occupational exposures appeared to linearly increase with increasing duration. Within these categories, occupational exposure to 14 subtypes of agents conferred significantly higher risks of NPC, with ORs ranging from 1.30 to 2.29, including dust from metals, textiles, cement, or coal; vapor from formaldehyde, organic solvents, or dyes; exhaust or smoke from diesel, firewood, asphalt/tar, vehicles, or welding; and sulfuric acid, hydrochloric acid, nitric acid, and concentrated alkali/ammonia.

Conclusions: Occupational exposures to dusts, chemical vapors, exhausts/smokes, or acids/alkalis are associated with an excess risk of NPC. If the current results are causal, then the amelioration of workplace conditions might alleviate the burden of NPC in endemic areas.

Lay Summary: The role of occupational exposures in the development of nasopharyngeal carcinoma (NPC) remains unclear, particularly in high-incidence areas. The authors conducted a population-based study with 2514 incident NPC cases and 2586 population controls in southern China and observed that occupational exposures were associated with an increased risk of NPC. Duration-response trends were observed with increasing duration of exposure. These findings provide new evidence supporting an etiologic role of occupational exposures for NPC in a high-incidence region.
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http://dx.doi.org/10.1002/cncr.33536DOI Listing
August 2021

Association of the Age at Menarche with Site-Specific Cancer Risks in Pooled Data from Nine Cohorts.

Cancer Res 2021 04 5;81(8):2246-2255. Epub 2021 Apr 5.

Division of Cancer Epidemiology and Genetics, National Institutes of Health, Rockville, Maryland.

The average age at menarche declined in European and U.S. populations during the 19th and 20th centuries. The timing of pubertal events may have broad implications for chronic disease risks in aging women. Here we tested for associations of recalled menarcheal age with risks of 19 cancers in 536,450 women [median age, 60 years (range, 31-39 years)] in nine prospective U.S. and European cohorts that enrolled participants from 1981 to 1998. Cox regression estimated multivariable-adjusted HRs and 95% confidence intervals (CI) for associations of the age at menarche with risk of each cancer in each cohort and random-effects meta-analysis was used to generate summary estimates for each cancer. Over a median 10 years of follow-up, 60,968 women were diagnosed with a first primary incident cancer. Inverse linear associations were observed for seven of 19 cancers studied. Each additional year in the age at menarche was associated with reduced risks of endometrial cancer (HR = 0.91; 95% CI, 0.89-0.94), liver cancer (HR = 0.92; 95% CI, 0.85-0.99), melanoma (HR = 0.95; 95% CI, 0.93-0.98), bladder cancer (HR = 0.96; 95% CI, 0.93-0.99), and cancers of the colon (HR = 0.97; 95% CI, 0.96-0.99), lung (HR = 0.98; 95% CI, 0.96-0.99), and breast (HR = 0.98; 95% CI, 0.93-0.99). All but one of these associations remained statistically significant following adjustment for baseline body mass index. Similarities in the observed associations between menarche and seven cancers suggest shared underlying causes rooted early in life. We propose as a testable hypothesis that early exposure to sex hormones increases mid-life cancer risks by altering functional capacities of stem cells with roles in systemic energy balance and tissue homeostasis. SIGNIFICANCE: Age at menarche is associated with risk for seven cancers in middle-aged women, and understanding the shared underlying causal pathways across these cancers may suggest new avenues for cancer prevention.
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http://dx.doi.org/10.1158/0008-5472.CAN-19-3093DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8137527PMC
April 2021

Randomized Trial for Weight Loss Using a Digital Therapeutic Application.

J Diabetes Sci Technol 2021 Mar 19:19322968211000815. Epub 2021 Mar 19.

Faculty of Medicine, University of Iceland and Children's Medical Centre, Landspitali University Hospital, Reykjavik, Iceland.

Background: Smartphones present a near-ubiquitous channel through which structured lifestyle change can reduce risk or progression of the most common noncommunicable diseases. We explored whether a digital structured lifestyle program enhances weight loss.

Methods: We randomized overweight and obese participants attending a four-month lifestyle change program to either standard weekly coaching sessions (controls), or standard treatment supplemented with a digital therapeutic mobile application (intervention). Changes in body mass index after four months were the main outcome measure. Odds ratios of achieving 5% weight loss were estimated with unconditional logistic regression.

Results: Of 234 eligible persons, 146 (62%) agreed to participate, were block-randomized, showed up for the baseline measures, and constituted the intention-to-treat (ITT) sample ( = 95 intervention group,  = 51 control group). In the intervention group, 70 (74%) downloaded the mobile application and completed the program (intervention per-protocol). Significant weight loss and BMI reduction were observed for both the intention-to-treat intervention group ( < 0.05,  = 0.01) and the per-protocol intervention group ( < 0.0001,  < 0.0001). For the intervention per-protocol group, the odds ratio of achieving 5% weight loss, compared to not treated per-protocol, was 3.3 (95% CI 1.3-8.2), adjusting for age and weight at baseline.Attendance to weekly coaching sessions decreased by 18% during the program in the control group while it increased by 3% amongst the per-protocol group ( = 0.004).

Conclusions: These preliminary findings support the benefit of a digital therapeutic to enhance weight reduction and attendance in a structured lifestyle change program. Larger trials of longer duration are needed to confirm these findings.
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http://dx.doi.org/10.1177/19322968211000815DOI Listing
March 2021

Residence characteristics and risk of nasopharyngeal carcinoma in southern China: A population-based case-control study.

Environ Int 2021 06 27;151:106455. Epub 2021 Feb 27.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Epidemiology and Health Statistics & Key Laboratory of Ministry of Education for Gastrointestinal Cancer, Fujian Medical University, Fuzhou, China. Electronic address:

Objectives: Given the role of exposures related to residence in the development of nasopharyngeal carcinoma (NPC) has not been well explored, present study aims to investigate the magnitude and pattern of associations for NPC with lifelong residential exposures.

Materials And Methods: We carried out a multi-center, population-based case-control study with 2533 incident NPC cases and 2597 randomly selected population controls in southern China between 2010 and 2014. We performed multivariate logistic regression to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the risk of NPC associated with residential exposures.

Results: Compared with those living in a building over lifetime, risk of NPC was higher for individuals living in a cottage (OR: 1.56; 95% CI: 1.34-1.81) or in a boat (3.87; 2.07-7.21). NPC risk was also increased in individuals using wood (1.34; 1.03-1.75), coal (1.70; 1.17-2.47), or kerosene (3.58; 1.75-7.36) vs. using gas/electricity as cooking fuel; using well water (1.57; 1.34-1.83), river water (1.80; 1.47-2.21), or spring/pond/stream water (2.03; 1.70-2.41) vs. tap water for source of drinking water; living in houses with smaller-sized vs. larger windows in the bedroom (3.08; 2.46-3.86), hall (1.89; 1.55-2.31) or kitchen (1.67; 1.34-2.08); and increasing exposure to cooking smoke [(1.53; 1.20-1.94) for high exposure)] or burned incense [(1.59; 1.31-1.95) for daily use)]. Weighted Cox regression analysis corroborated these results.

Conclusion: Poorer residential conditions and household air pollution are associated with an increased risk of NPC. Large-scale studies in other populations or longitudinal studies are warranted to further corroborate these findings.
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http://dx.doi.org/10.1016/j.envint.2021.106455DOI Listing
June 2021

Deep learning and cancer biomarkers: recognising lead-time bias.

Lancet 2021 01;397(10270):194

Clinical Effectiveness Research Group, University of Oslo and Oslo University Hospital, Oslo 0318, Norway.

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http://dx.doi.org/10.1016/S0140-6736(20)32402-8DOI Listing
January 2021

Effects of alcohol consumption and smoking on risk for RA: results from a Swedish prospective cohort study.

RMD Open 2021 01;7(1)

Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.

Objective: Several, but not all studies, have shown a dose-dependent inverse association with alcohol consumption and rheumatoid arthritis (RA), whereas smoking is an established risk factor for RA. We aimed to study the association between alcohol consumption and RA incidence and investigate a potential interaction between alcohol and smoking habits, regarding RA incidence.

Methods: We used a prospective cohort study, based on 41 068 participants with detailed assessment of alcohol intake, smoking and potential confounders at baseline in 1997. We ascertained a total of 577 incident cases of RA during a mean of 17.7 years of follow-up through linkage to nationwide and essentially complete databases. Multivariate Cox proportional hazards models were used to estimate HR with 95% CI. Interaction on the additive scale between alcohol and smoking was estimated by calculating the attributable proportion due to interaction (AP).

Results: Overall, alcohol consumption was associated with a 30% reduced incidence of RA (HR 0.69, 95% CI 0.55 to 0.86) with a dose-response relationship (p value for trend <0.001) which remained significant after stratification by age and smoking habits. The positive association between smoking and RA incidence was reduced with increasing alcohol consumption (p value for trend <0.001). A synergistic effect was observed between alcohol and smoking (AP 0.40, 95% CI 0.15 to 0.64), indicating that 40% of the cases among the double exposed are due to the interaction per se.

Conclusions: Our findings suggest an inverse association between alcohol consumption and RA incidence, and a synergistic effect between alcohol and smoking.
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http://dx.doi.org/10.1136/rmdopen-2020-001379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7797247PMC
January 2021

Dietary Antioxidants and the Risk of Parkinson Disease: The Swedish National March Cohort.

Neurology 2021 02 6;96(6):e895-e903. Epub 2021 Jan 6.

From the Department of Statistics and Quantitative Methods (E.H., R.B.), University of Milano-Bicocca, Milan; Institute for Biomedicine, Eurac Research (E.H.), Affiliated Institute of the University of Lübeck, Bolzano, Italy; Clinical Epidemiology Division, Department of Medicine (Solna) (Y.T.L., S.B.), and Department of Medical Epidemiology and Biostatistics (W.Y., H.-O.A., R.B.), Karolinska Institutet, Stockholm; Obesity Center, Academic Specialist Center (Y.T.L.), Stockholm Health Services, Sweden; Functional Food and Metabolic Stress Prevention Laboratory, Faculty of BioSciences and Technology for Food, Agriculture and Environment (M.S.), University of Teramo, Italy; and Clinical Effectiveness Research Group, Institute of Health (H.-O.A.), University of Oslo, Norway.

Objective: To determine whether high baseline dietary antioxidants and total nonenzymatic antioxidant capacity (NEAC) is associated with a lower risk of Parkinson disease (PD) in men and women, we prospectively studied 43,865 men and women from a large Swedish cohort.

Methods: In the Swedish National March Cohort, 43,865 men and women aged 18-94 years were followed through record linkages to National Health Registries from 1997 until 2016. Baseline dietary vitamin E, vitamin C, and beta-carotene intake, as well as NEAC, were assessed by a validated food frequency questionnaire collected at baseline. All exposure variables were adjusted for energy intake and categorized into tertiles. Multivariable Cox proportional hazard regression models were fitted to estimate hazard ratios (HRs) with 95% confidence intervals (CIs) for PD.

Results: After a mean follow-up time of 17.6 years, we detected 465 incidence cases of PD. In the multivariable adjusted model, dietary vitamin E (HR 0.68, 95% CI 0.52-0.90; for trend 0.005) and vitamin C (HR 0.68, 95% CI 0.52-0.89; for trend 0.004) were inversely associated with the risk of PD when comparing participants in the highest vs the lowest tertiles of exposure. No association was found with estimated intake of dietary beta-carotene or NEAC.

Conclusion: Our findings suggest that dietary vitamin E and C intake might be inversely associated with the risk of PD. No association was found with dietary beta-carotene or NEAC.

Classification Of Evidence: This study provides Class III evidence that dietary vitamin E and C intake are inversely associated with the risk of PD.
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http://dx.doi.org/10.1212/WNL.0000000000011373DOI Listing
February 2021

Intake of Alcohol and Tea and Risk of Nasopharyngeal Carcinoma: A Population-Based Case-Control Study in Southern China.

Cancer Epidemiol Biomarkers Prev 2021 03 10;30(3):545-553. Epub 2020 Dec 10.

Department of Cancer Prevention Center, Sun Yat-sen University Cancer Center, Guangzhou, China.

Background: The potential effect of alcohol or tea intake on the risk of nasopharyngeal carcinoma (NPC) remains controversial.

Methods: In a population-based case-control study in southern China, we assessed alcohol or tea intake from 2,441 histopathologically confirmed NPC cases and 2,546 controls. We calculated mean daily ethanol (g/day) and tea intake (mL/day). Fully adjusted ORs with 95% confidence intervals (CI) were estimated using logistic regression; potential dose-response trends were evaluated using restricted cubic spline analysis.

Results: Compared with nondrinkers, no significantly increased NPC risk in men was observed among current alcohol drinkers overall (OR, 1.08; 95% CI, 0.93-1.25), nor among current heavy drinkers (OR for ≥90 g/day ethanol vs. none, 1.32; 95% CI, 0.95-1.84) or former alcohol drinkers. Current tea drinking was associated with a decreased NPC risk (OR, 0.73; 95% CI, 0.64-0.84). Compared with never drinkers, those with the low first three quintiles of mean daily current intake of tea were at significantly lower NPC risk (OR, 0.53, 0.68, and 0.65, respectively), but not significant for the next two quintiles. Current daily tea intake had a significant nonlinear dose-response relation with NPC risk.

Conclusions: Our study suggests no significant association between alcohol and NPC risk. Tea drinking may moderately reduce NPC risk, but the lack of a monotonic dose-response association complicates causal inference.

Impact: Tea drinking might be a healthy habit for preventing NPC. More studies on biological mechanisms that may link tea with NPC risk are needed.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1244DOI Listing
March 2021

Neighborhood greenness and burden of non-communicable diseases in Sub-Saharan Africa: A multi-country cross-sectional study.

Environ Res 2021 05 31;196:110397. Epub 2020 Oct 31.

Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, USA; Channing Division of Network Medicine, Brigham & Women's Hospital, Harvard Medical School, Boston, USA.

Population growth, demographic transitions and urbanization in sub-Saharan Africa (SSA) will increase non-communicable disease (NCD) burden. We studied the association between neighborhood greenness and NCDs in a multi-country cross-sectional study. Among 1178 participants, in adjusted models, a 0.11 unit NDVI increase was associated with lower BMI (β: -1.01, 95% CI: -1.35, -0.67), and lower odds of overweight/obesity (aOR: 0.73, 95% CI: 0.62, 0.85), diabetes (aOR: 0.77, 95% CI: 0.62, 0.96), and having ≥3 allostatic load components compared to none (aOR: 0.66, 95% CI: 0.52, 0.85). Except for diabetes, these remained statistically significant after Bonferroni correction. We observed no association between NDVI and hypertension or cholesterol. Our findings are consistent with health benefits of neighborhood greenness reported in other countries, suggesting greening strategies could be considered as part of broader public health interventions for NCDs.
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http://dx.doi.org/10.1016/j.envres.2020.110397DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8085185PMC
May 2021

Body size and weight change over adulthood and risk of breast cancer by menopausal and hormone receptor status: a pooled analysis of 20 prospective cohort studies.

Eur J Epidemiol 2021 Jan 30;36(1):37-55. Epub 2020 Oct 30.

Epidemiology and Prevention Group, Research Center for Cancer Prevention and Screening, National Cancer Center, Tokyo, Japan.

Associations between anthropometric factors and breast cancer (BC) risk have varied inconsistently by estrogen and/or progesterone receptor (ER/PR) status. Associations between prediagnostic anthropometric factors and risk of premenopausal and postmenopausal BC overall and ER/PR status subtypes were investigated in a pooled analysis of 20 prospective cohorts, including 36,297 BC cases among 1,061,915 women, using multivariable Cox regression analyses, controlling for reproductive factors, diet and other risk factors. We estimated dose-response relationships and tested for nonlinear associations using restricted cubic splines. Height showed positive, linear associations for premenopausal and postmenopausal BC risk (6-7% RR increase per 5 cm increment), with stronger associations for receptor-positive subtypes. Body mass index (BMI) at cohort baseline was strongly inversely associated with premenopausal BC risk, and strongly positively-and nonlinearly-associated with postmenopausal BC (especially among women who never used hormone replacement therapy). This was primarily observed for receptor-positive subtypes. Early adult BMI (at 18-20 years) showed inverse, linear associations for premenopausal and postmenopausal BC risk (21% and 11% RR decrease per 5 kg/m, respectively) with stronger associations for receptor-negative subtypes. Adult weight gain since 18-20 years was positively associated with postmenopausal BC risk, stronger for receptor-positive subtypes, and among women who were leaner in early adulthood. Women heavier in early adulthood generally had reduced premenopausal BC risk, independent of later weight gain. Positive associations between height, baseline (adult) BMI, adult weight gain and postmenopausal BC risk were substantially stronger for hormone receptor-positive versus negative subtypes. Premenopausal BC risk was positively associated with height, but inversely with baseline BMI and weight gain (mostly in receptor-positive subtypes). Inverse associations with early adult BMI seemed stronger in receptor-negative subtypes of premenopausal and postmenopausal BC.
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http://dx.doi.org/10.1007/s10654-020-00688-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7847460PMC
January 2021

Pregnancy outcomes and risk of endometrial cancer: A pooled analysis of individual participant data in the Epidemiology of Endometrial Cancer Consortium.

Int J Cancer 2021 05 17;148(9):2068-2078. Epub 2020 Nov 17.

Department of Clinical and Biological Sciences, University of Turin, Orbassano, Italy.

A full-term pregnancy is associated with reduced endometrial cancer risk; however, whether the effect of additional pregnancies is independent of age at last pregnancy is unknown. The associations between other pregnancy-related factors and endometrial cancer risk are less clear. We pooled individual participant data from 11 cohort and 19 case-control studies participating in the Epidemiology of Endometrial Cancer Consortium (E2C2) including 16 986 women with endometrial cancer and 39 538 control women. We used one- and two-stage meta-analytic approaches to estimate pooled odds ratios (ORs) for the association between exposures and endometrial cancer risk. Ever having a full-term pregnancy was associated with a 41% reduction in risk of endometrial cancer compared to never having a full-term pregnancy (OR = 0.59, 95% confidence interval [CI] 0.56-0.63). The risk reduction appeared the greatest for the first full-term pregnancy (OR = 0.78, 95% CI 0.72-0.84), with a further ~15% reduction per pregnancy up to eight pregnancies (OR = 0.20, 95% CI 0.14-0.28) that was independent of age at last full-term pregnancy. Incomplete pregnancy was also associated with decreased endometrial cancer risk (7%-9% reduction per pregnancy). Twin births appeared to have the same effect as singleton pregnancies. Our pooled analysis shows that, while the magnitude of the risk reduction is greater for a full-term pregnancy than an incomplete pregnancy, each additional pregnancy is associated with further reduction in endometrial cancer risk, independent of age at last full-term pregnancy. These results suggest that the very high progesterone level in the last trimester of pregnancy is not the sole explanation for the protective effect of pregnancy.
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http://dx.doi.org/10.1002/ijc.33360DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7969437PMC
May 2021

Assessment of cancer screening effectiveness in the era of screening programs.

Eur J Epidemiol 2020 Oct 14;35(10):891-897. Epub 2020 Sep 14.

Department of Epidemiology, Harvard T. H. Chan School of Public Health, Boston, MA, USA.

Whilst the benefit of detecting and removing cancer precursors in the cervix and the large bowel is unequivocally documented, the balance between benefit and harm due to screening for early detection of breast and prostate cancer remains uncertain after 30-50 years of randomized control trials (RCTs). Concomitantly, traditional RCTs become increasingly unfeasible due to low compliance, contamination of control groups, difficulties to enroll screening naïve individuals, and prohibitively high costs. Therefore, we have systematically reviewed pros and cons with alternative study designs to quantify screening effectiveness. Whilst traditional RCTs should remain gold standard whenever feasible, observational cohort and case-control studies are unlikely to provide the valid evidence needed for health policy decisions. Instead, we advocate two methodological approaches that are novel in assessment of cancer screening effectiveness. One-the difference-in-difference design, well established in health policy and public health research-has a sophisticated ecologic design which unfortunately is feasible only in few countries. Another implies that sequential RCTs become embedded whenever population-based screening programs are implemented.
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http://dx.doi.org/10.1007/s10654-020-00684-7DOI Listing
October 2020

Towards a cancer mission in Horizon Europe: recommendations.

Mol Oncol 2020 08;14(8):1589-1615

European Cancer Patient Coalition, Brussels, Belgium.

A comprehensive translational cancer research approach focused on personalized and precision medicine, and covering the entire cancer research-care-prevention continuum has the potential to achieve in 2030 a 10-year cancer-specific survival for 75% of patients diagnosed in European Union (EU) member states with a well-developed healthcare system. Concerted actions across this continuum that spans from basic and preclinical research through clinical and prevention research to outcomes research, along with the establishment of interconnected high-quality infrastructures for translational research, clinical and prevention trials and outcomes research, will ensure that science-driven and social innovations benefit patients and individuals at risk across the EU. European infrastructures involving comprehensive cancer centres (CCCs) and CCC-like entities will provide researchers with access to the required critical mass of patients, biological materials and technological resources and can bridge research with healthcare systems. Here, we prioritize research areas to ensure a balanced research portfolio and provide recommendations for achieving key targets. Meeting these targets will require harmonization of EU and national priorities and policies, improved research coordination at the national, regional and EU level and increasingly efficient and flexible funding mechanisms. Long-term support by the EU and commitment of Member States to specialized schemes are also needed for the establishment and sustainability of trans-border infrastructures and networks. In addition to effectively engaging policymakers, all relevant stakeholders within the entire continuum should consensually inform policy through evidence-based advice.
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http://dx.doi.org/10.1002/1878-0261.12763DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400777PMC
August 2020

Subspecies Niche Specialization in the Oral Microbiome Is Associated with Nasopharyngeal Carcinoma Risk.

mSystems 2020 Jul 7;5(4). Epub 2020 Jul 7.

Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden

Oral health and changes in the oral microbiome have been associated with both local and systemic cancer. Poor oral hygiene is a known risk factor for nasopharyngeal carcinoma (NPC), a virally associated head and neck cancer endemic to southern China. We explored the relationship between NPC and the oral microbiome using 16S rRNA sequencing in a study of 499 NPC patients and 495 population-based age and sex frequency-matched controls from an area of endemicity of Southern China. We found a significant reduction in community richness in cases compared to that in controls. Differences in the overall microbial community structure between cases and controls could not be explained by other potential confounders; disease status explained 5 times more variation in the unweighted UniFrac distance than the next most explanatory variable. In feature-based analyses, we identified a pair of coexcluding amplicon sequence variants (ASVs) which were strongly associated with NPC status and differed by a single nucleotide. The variant an individual carried was also associated with the overall microbial community based on beta diversity. Co-occurrence analysis suggested the two ASVs sit at the center of two coexcluding clusters of closely related organisms. Our results suggest there are differences in the oral microbiomes between NPC patients and healthy controls, and these may be associated with both a loss of microbial diversity and niche specialization among closely related commensals. The relationship between oral health and the risk of nasopharyngeal carcinoma (NPC) was previously established. However, the role of oral microbiome has not been evaluated in the disease in a large epidemiological study. This paper clearly establishes a difference in the oral microbiomes between NPC patients and healthy controls which cannot be explained by other confounding factors. It furthermore identifies a pair of closely related coexcluding organisms associated with the disease, highlighting the importance of modern methods for single-nucleotide resolution in 16S rRNA sequence characterization. To the best of our knowledge, this is one of the first examples of cancer-associated niche specialization of the oral microbiome.
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http://dx.doi.org/10.1128/mSystems.00065-20DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7343305PMC
July 2020

Prospective study of job stress and risk of infections in Swedish adults.

Occup Environ Med 2020 10 23;77(10):681-690. Epub 2020 Jun 23.

Department of Medicine, Clinical Epidemiology Unit, Karolinska Institutet, Stockholm, Sweden.

Objectives: Psychological stress may influence both susceptibility and severity of infections. Although work-related stress is a widespread concern among many employees, few studies have been conducted with the focus on work stressors and infections. We therefore aimed to investigate this association in a prospective cohort study.

Methods: Our study included 25 029 employed individuals who filled-out a questionnaire in September 1997 and were followed through record linkages until retirement or December 2016. Work stress was assessed at baseline using a Swedish version of the Demand-Control Questionnaire, whereas hospital contacts related to infections were identified from the National Patient Register. We fitted extensions of the standard Cox model to account for recurrent infections.

Results: In total, we observed 8257 infections. Individuals in the third tertile of job demand had a 13% higher hazard of infections (HR=1.13; 95% CI=1.03 to 1.24) compared with individuals in the first tertile, specifically an increased incidence of upper respiratory tract infections (HR=1.15; 95% CI=1.00 to 1.33) and urinary tract infections (HR=1.31; 95% CI=1.09 to 1.57) was found. Employees with the highest job control (third tertile) had no lower risk of infections than individuals in the lowest tertile (HR=1.02; 95% CI=0.92 to 1.13). When combining the demand and control dimensions into job strain scale, no association between high job strain and infections was observed (HR=1.08; 95% CI=0.97 to 1.21).

Conclusion: High job demand, but not low job control, is associated with an increased occurrence of infections. No difference was observed in workers with high strain jobs compared with those with low strain jobs.
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http://dx.doi.org/10.1136/oemed-2020-106489DOI Listing
October 2020

Breast Cancer Screening and Diagnosis.

Ann Intern Med 2020 06;172(12):839-840

University of Strathclyde Institute of Global Public Health, International Prevention Research Institute, Lyon, France (P.A.).

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http://dx.doi.org/10.7326/L20-0252DOI Listing
June 2020

Associations between reproductive factors and biliary tract cancers in women from the Biliary Tract Cancers Pooling Project.

J Hepatol 2020 10 11;73(4):863-872. Epub 2020 May 11.

Epidemiology Branch, National Institute of Environmental Health Sciences, Research Triangle Park, NC, USA.

Background & Aims: Gallbladder cancer (GBC) is known to have a female predominance while other biliary tract cancers (BTCs) have a male predominance. However, the role of female reproductive factors in BTC etiology remains unclear.

Methods: We pooled data from 19 studies of >1.5 million women participating in the Biliary Tract Cancers Pooling Project to examine the associations of parity, age at menarche, reproductive years, and age at menopause with BTC. Associations for age at menarche and reproductive years with BTC were analyzed separately for Asian and non-Asian women. Hazard ratios (HRs) and 95% CIs were estimated using Cox proportional hazards models, stratified by study.

Results: During 21,681,798 person-years of follow-up, 875 cases of GBC, 379 of intrahepatic bile duct cancer (IHBDC), 450 of extrahepatic bile duct cancer (EHBDC), and 261 of ampulla of Vater cancer (AVC) occurred. High parity was associated with risk of GBC (HR ≥5 vs. 0 births 1.72; 95% CI 1.25-2.38). Age at menarche (HR per year increase 1.15; 95% CI 1.06-1.24) was associated with GBC risk in Asian women while reproductive years were associated with GBC risk (HR per 5 years 1.13; 95% CI 1.04-1.22) in non-Asian women. Later age at menarche was associated with IHBDC (HR 1.19; 95% CI 1.09-1.31) and EHBDC (HR 1.11; 95% CI 1.01-1.22) in Asian women only.

Conclusion: We observed an increased risk of GBC with increasing parity. Among Asian women, older age at menarche was associated with increased risk for GBC, IHBDC, and EHBDC, while increasing reproductive years was associated with GBC in non-Asian women. These results suggest that sex hormones have distinct effects on cancers across the biliary tract that vary by geography.

Lay Summary: Our findings show that the risk of gallbladder cancer is increased among women who have given birth (especially women with 5 or more children). In women from Asian countries, later age at menarche increases the risk of gallbladder cancer, intrahepatic bile duct cancer and extrahepatic bile duct cancer. We did not see this same association in women from Western countries. Age at menopause was not associated with the risk of any biliary tract cancers.
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http://dx.doi.org/10.1016/j.jhep.2020.04.046DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7901003PMC
October 2020

Genetically Determined Height and Risk of Non-hodgkin Lymphoma.

Front Oncol 2019 28;9:1539. Epub 2020 Jan 28.

Interdisciplinary Department of Medicine, University of Bari, Bari, Italy.

Although the evidence is not consistent, epidemiologic studies have suggested that taller adult height may be associated with an increased risk of some non-Hodgkin lymphoma (NHL) subtypes. Height is largely determined by genetic factors, but how these genetic factors may contribute to NHL risk is unknown. We investigated the relationship between genetic determinants of height and NHL risk using data from eight genome-wide association studies (GWAS) comprising 10,629 NHL cases, including 3,857 diffuse large B-cell lymphoma (DLBCL), 2,847 follicular lymphoma (FL), 3,100 chronic lymphocytic leukemia (CLL), and 825 marginal zone lymphoma (MZL) cases, and 9,505 controls of European ancestry. We evaluated genetically predicted height by constructing polygenic risk scores using 833 height-associated SNPs. We used logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI) for association between genetically determined height and the risk of four NHL subtypes in each GWAS and then used fixed-effect meta-analysis to combine subtype results across studies. We found suggestive evidence between taller genetically determined height and increased CLL risk (OR = 1.08, 95% CI = 1.00-1.17, = 0.049), which was slightly stronger among women (OR = 1.15, 95% CI: 1.01-1.31, = 0.036). No significant associations were observed with DLBCL, FL, or MZL. Our findings suggest that there may be some shared genetic factors between CLL and height, but other endogenous or environmental factors may underlie reported epidemiologic height associations with other subtypes.
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http://dx.doi.org/10.3389/fonc.2019.01539DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6999122PMC
January 2020

Adult weight change and premenopausal breast cancer risk: A prospective pooled analysis of data from 628,463 women.

Int J Cancer 2020 09 15;147(5):1306-1314. Epub 2020 Feb 15.

Albert Einstein College of Medicine, Bronx, NY.

Early-adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual-level data from 17 prospective studies to investigate the association of weight change with premenopausal breast cancer risk, considering strata of initial weight, timing of weight change, other breast cancer risk factors and breast cancer subtype. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained using Cox regression. Among 628,463 women, 10,886 were diagnosed with breast cancer before menopause. Models adjusted for initial weight at ages 18-24 years and other breast cancer risk factors showed that weight gain from ages 18-24 to 35-44 or to 45-54 years was inversely associated with breast cancer overall (e.g., HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.95-0.98) and with oestrogen-receptor(ER)-positive breast cancer (HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.94-0.98). Weight gain from ages 25-34 was inversely associated with ER-positive breast cancer only and weight gain from ages 35-44 was not associated with risk. None of these weight gains were associated with ER-negative breast cancer. Weight loss was not consistently associated with overall or ER-specific risk after adjusting for initial weight. Weight increase from early-adulthood to ages 45-54 years is associated with a reduced premenopausal breast cancer risk independently of early-adulthood weight. Biological explanations are needed to account for these two separate factors.
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http://dx.doi.org/10.1002/ijc.32892DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7365745PMC
September 2020

Evaluation of the antibody response to the EBV proteome in EBV-associated classical Hodgkin lymphoma.

Int J Cancer 2020 08 14;147(3):608-618. Epub 2019 Nov 14.

Division of Cancer Epidemiology and Genetics, National Cancer Institute, Rockville, MD.

The humoral immune response to Epstein-Barr virus (EBV) in classical Hodgkin lymphoma (cHL) stratified by EBV tumor status is unclear. We examined IgG and IgA antibody responses against 202 protein sequences representing 86 EBV proteins using a microarray and sera from 139 EBV-positive cHL cases, 70 EBV-negative cHL cases and 141 population-based controls frequency matched to EBV-positive cHL cases on sex and age by area (UK, Denmark and Sweden). We leveraged existing data on the proportion of circulating B-cells infected by EBV and levels of serum CCL17, a chemokine secreted by cHL tumor cells, from a subset of the cHL cases in the UK. Total IgG but not IgA response level was significantly different between EBV-positive cHL cases and controls. The distinct serological response included significant elevations in 16 IgG antibodies and 2 IgA antibodies, with odds ratios observed for the following EBV proteins: LMP1 (oncogene), BcLF1 (VCAp160, two variants) and BBLF1 (two variants). Our cHL IgG signature correlated with the proportion of circulating EBV-infected B-cells, but not serum CCL17 levels. We observed no differences in the anti-EBV antibody profile between EBV-negative cHL cases and controls. BdRF1(VCAp40)-IgG and BZLF1(Zta)-IgG were identified as the serological markers best able to distinguish EBV-positive from EBV-negative cHL tumors. Our results support the hypothesis that differences in the EBV antibody profile are specific to patients with EBV-positive cHL and are not universally observed as part of a systematically dysregulated immune response present in all cHL cases.
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http://dx.doi.org/10.1002/ijc.32741DOI Listing
August 2020

Age at natural menopause and risk of incident cardiovascular disease: a pooled analysis of individual patient data.

Lancet Public Health 2019 11 3;4(11):e553-e564. Epub 2019 Oct 3.

School of Public Health, University of Queensland, Brisbane, QLD, Australia. Electronic address:

Background: Early menopause is linked to an increased risk of cardiovascular disease mortality; however, the association between early menopause and incidence and timing of cardiovascular disease is unclear. We aimed to assess the associations between age at natural menopause and incidence and timing of cardiovascular disease.

Methods: We harmonised and pooled individual-level data from 15 observational studies done across five countries and regions (Australia, Scandinavia, the USA, Japan, and the UK) between 1946 and 2013. Women who had reported their menopause status, age at natural menopause (if postmenopausal), and cardiovascular disease status (including coronary heart disease and stroke) were included. We excluded women who had hysterectomy or oophorectomy and women who did not report their age at menopause. The primary endpoint of this study was the occurrence of first non-fatal cardiovascular disease, defined as a composite outcome of incident coronary heart disease (including heart attack and angina) or stroke (including ischaemic stroke or haemorrhagic stroke). We used Cox proportional hazards models to estimate multivariate hazard ratios (HRs) and 95% CIs for the associations between age at menopause and incident cardiovascular disease event. We also adjusted the model to account for smoking status, menopausal hormone therapy status, body-mass index, and education levels. Age at natural menopause was categorised as premenopausal or perimenopausal, younger than 40 years (premature menopause), 40-44 years (early menopause), 45-49 years (relatively early), 50-51 years (reference category), 52-54 years (relatively late), and 55 years or older (late menopause).

Findings: Overall, 301 438 women were included in our analysis. Of these 301 438 women, 12 962 (4·3%) had a first non-fatal cardiovascular disease event after menopause, of whom 9369 (3·1%) had coronary heart disease and 4338 (1·4%) had strokes. Compared with women who had menopause at age 50-51 years, the risk of cardiovascular disease was higher in women who had premature menopause (age <40 years; HR 1·55, 95% CI 1·38-1·73; p<0·0001), early menopause (age 40-44 years; 1·30, 1·22-1·39; p<0·0001), and relatively early menopause (age 45-49 years; 1·12, 1·07-1·18; p<0·0001), with a significantly reduced risk of cardiovascular disease following menopause after age 51 years (p<0·0001 for trend). The associations persisted in never smokers, and were strongest before age 60 years for women with premature menopause (HR 1·88, 1·62-2·20; p<0·0001) and early menopause (1·40, 1·27-1·54; p<0·0001), but were attenuated at age 60-69 years, with no significant association observed at age 70 years and older.

Interpretation: Compared with women who had menopause at age 50-51 years, women with premature and early menopause had a substantially increased risk of a non-fatal cardiovascular disease event before the age of 60 years, but not after age 70 years. Women with earlier menopause need close monitoring in clinical practice, and age at menopause might also be considered as an important factor in risk stratification of cardiovascular disease for women.

Funding: Australian National Health and Medical Research Council.
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http://dx.doi.org/10.1016/S2468-2667(19)30155-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7118366PMC
November 2019

Chinese nonmedicinal herbal diet and risk of nasopharyngeal carcinoma: A population-based case-control study.

Cancer 2019 12 22;125(24):4462-4470. Epub 2019 Sep 22.

Department of Cancer Prevention Center, Sun Yat-Sen University Cancer Center, Guangzhou, China.

Background: An association between a nonmedicinal herbal diet and nasopharyngeal carcinoma (NPC) has often been hypothesized but never thoroughly investigated.

Methods: This study enrolled a total of 2469 patients with incident NPC and 2559 population controls from parts of Guangdong and Guangxi Provinces in southern China between 2010 and 2014. Questionnaire information was collected on the intake of traditional herbal tea and herbal soup as well as the specific herbal plants used in soups and other potentially confounding lifestyle factors. Multivariate logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (CIs) for the NPC risk in association with herbal tea and soup intake.

Results: Ever consumption of herbal tea was not associated with NPC risk (OR, 1.03; 95% CI, 0.91-1.17). An inverse association was observed for NPC among ever drinkers of herbal soup (OR, 0.78; 95% CI, 0.67-0.90) but without any monotonic trend with an increasing frequency or duration of herbal soup consumption. Inverse associations with NPC risk were detected with 9 herbal plants used in herbal soup, including Ziziphus jujuba, Fructus lycii, Codonopsis pilosula, Astragalus membranaceus, Semen coicis, Smilax glabra, Phaseolus calcaratus, Morinda officinalis, and Atractylodes macrocephala (OR range, 0.31-0.79).

Conclusions: Consuming herbal soups including specific plants, but not herbal tea, was inversely associated with NPC. If replicated, these results might provide potential for NPC prevention in endemic areas.
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http://dx.doi.org/10.1002/cncr.32458DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6891117PMC
December 2019

The Nordic Twin Study on Cancer - NorTwinCan.

Twin Res Hum Genet 2019 12 12;22(6):817-823. Epub 2019 Sep 12.

Department of Public Health and Institute for Molecular Medicine, University of Helsinki, Helsinki, Finland.

Nordic twin studies have played a critical role in understanding cancer etiology and elucidating the nature of familial effects on site-specific cancers. The NorTwinCan consortium is a collaborative effort that capitalizes on unique research advantages made possible through the Nordic system of registries. It was constructed by linking the population-based twin registries of Denmark, Finland, Norway and Sweden to their country-specific national cancer and cause-of-death registries. These linkages enable the twins to be followed many decades for cancer incidence and mortality. To date, two major linkages have been conducted: NorTwinCan I in 2011-2012 and NorTwinCan II in 2018. Overall, there are 315,413 eligible twins, 57,236 incident cancer cases and 58 years of follow-up, on average. In the initial phases of our work, NorTwinCan established the world's most comprehensive twin database for studying cancer, developed novel analytical approaches tailored to address specific research considerations within the context of the Nordic data and leveraged these models and data in research publications that provide the most accurate estimates of heritability and familial risk of cancers reported in the literature to date. Our findings indicate an excess familial risk for nearly all cancers and demonstrate that the incidence of cancer among twins mirrors the rate in the general population. They also revealed that twin concordance for cancer most often manifests across, rather than within, cancer sites, and we are currently focusing on the analysis of these cross-cancer associations.
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http://dx.doi.org/10.1017/thg.2019.71DOI Listing
December 2019

PCASTt/SPCG-17-a randomised trial of active surveillance in prostate cancer: rationale and design.

BMJ Open 2019 08 22;9(8):e027860. Epub 2019 Aug 22.

Uppsala Universitet Institutionen for Kirurgiska Vetenskaper, Uppsala, Sweden.

Introduction: Overtreatment of localised prostate cancer is substantial despite increased use of active surveillance. No randomised trials help define how to monitor patients or when to initiate treatment with curative intent.

Methods And Analysis: A randomised, multicentre, intervention trial designed to evaluate the safety of an MRI-based active surveillance protocol, with standardised triggers for repeated biopsies and radical treatment. The aim is to reduce overtreatment of prostate cancer. 2000 men will be randomly allocated to either surveillance according to current practice or to standardised triggers at centres in Sweden, Norway, Finland and the UK. Men diagnosed in the past 12 months with prostate cancer, ≤T2a, prostate-specific antigen (PSA) <15 ng/mL, PSA density ≤0.2 ng/mL/cc, any International Society of Urological Pathology (ISUP) grade 1 are eligible. Men with ISUP grade 2 in <30% of cores on systematic biopsy and <10 mm cancer in one core on systematic or targeted biopsy are also eligible. Men diagnosed on systematic biopsy should have an MRI and targeted biopsies against Prostate Imaging and Reporting Data System V.2 3-5 lesions before inclusion. Identical follow-up in the two study arms: biannual PSA testing, yearly clinical examination and MRI every second year. In the experimental arm, standardised triggers based on MRI and PSA density elicit repeated biopsies. MRI and histopathological progression trigger radical treatment. Primary outcome measure is progression-free survival. Secondary outcome measures are cumulative incidence of metastatic disease, treatments with curative intent, pT3-4 at radical prostatectomy, switch to watchful waiting, prostate cancer mortality and quality of life. Inclusion started in October 2016 and in October 2018; 275 patients have been enrolled.

Ethics And Dissemination: Ethical approval was obtained in each participating country. Results for the primary and secondary outcome measures will be submitted for publication in peer-reviewed journals.

Trial Registration Number: NCT02914873.
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http://dx.doi.org/10.1136/bmjopen-2018-027860DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6707666PMC
August 2019

Genetic overlap between autoimmune diseases and non-Hodgkin lymphoma subtypes.

Genet Epidemiol 2019 10 13;43(7):844-863. Epub 2019 Aug 13.

Medicina Traslazionale, Università del Piemonte Orientale, Vercelli, Italy.

Epidemiologic studies show an increased risk of non-Hodgkin lymphoma (NHL) in patients with autoimmune disease (AD), due to a combination of shared environmental factors and/or genetic factors, or a causative cascade: chronic inflammation/antigen-stimulation in one disease leads to another. Here we assess shared genetic risk in genome-wide-association-studies (GWAS). Secondary analysis of GWAS of NHL subtypes (chronic lymphocytic leukemia, diffuse large B-cell lymphoma, follicular lymphoma, and marginal zone lymphoma) and ADs (rheumatoid arthritis, systemic lupus erythematosus, and multiple sclerosis). Shared genetic risk was assessed by (a) description of regional genetic of overlap, (b) polygenic risk score (PRS), (c)"diseasome", (d)meta-analysis. Descriptive analysis revealed few shared genetic factors between each AD and each NHL subtype. The PRS of ADs were not increased in NHL patients (nor vice versa). In the diseasome, NHLs shared more genetic etiology with ADs than solid cancers (p = .0041). A meta-analysis (combing AD with NHL) implicated genes of apoptosis and telomere length. This GWAS-based analysis four NHL subtypes and three ADs revealed few weakly-associated shared loci, explaining little total risk. This suggests common genetic variation, as assessed by GWAS in these sample sizes, may not be the primary explanation for the link between these ADs and NHLs.
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http://dx.doi.org/10.1002/gepi.22242DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6763347PMC
October 2019
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