Publications by authors named "Jan Sundquist"

654 Publications

Combined Use of Aspirin and Selective Serotonin Reuptake Inhibitors Is Associated With Lower Risk of Colorectal Cancer: A Nested Case-Control Study.

Authors:
Naiqi Zhang Jan Sundquist Kristina Sundquist Zhi-Gang Zhang Jianguang Ji

Am J Gastroenterol 2021 Feb 26. Epub 2021 Feb 26.

Center for Primary Health Care Research, Lund University/Region Skåne, Sweden; Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Center for Community-based Healthcare Research and Education (CoHRE), Department of Functional Pathology, School of Medicine, Shimane University, Japan; State Key Laboratory of Oncogenes and Related Genes, Shanghai Cancer Institute, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China..

Introduction: Chemoprevention against colorectal cancer (CRC) is greatly needed. As the development of CRC involves multiple dysfunctional pathways, it is thus reasonable to combine some agents that address several pathways to achieve better chemoprotection. We aimed to explore whether the use of aspirin and selective serotonin reuptake inhibitors (SSRIs)-either as monotherapy or combined-can have a clinical benefit against CRC.

Methods: We performed a nested case-control study using nationwide Swedish registers. We recruited 24,786 CRC cases and randomly matched to 74,358 controls conditional on birth year and sex using incidence-density sampling. The conditional logistic regression model was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs). Additive interaction was calculated as the relative excess risk for interaction, and multiplicative interaction was calculated by including a product term in the regression model.

Results: Both aspirin and SSRIs monotherapy were negatively associated with CRC risk, but the combined use of aspirin and SSRIs was associated with an even lower CRC risk (adjusted OR, 0.77, 95% CI, 0.67-0.89) than aspirin monotherapy (adjusted OR, 0.91, 95% CI, 0.87-0.97) or SSRI monotherapy (adjusted OR, 0.93, 95% CI, 0.86-1.00). A significant interaction was observed at the additive scale with a relative excess risk for interaction of -0.07 (P < 0.001), whereas no interaction was noted on the interactive scale. The inverse associations of CRC with aspirin and SSRIs showed a dose-dependent pattern.

Discussion: This study suggests that the use of aspirin and SSRIs-either as monotherapy or combined-was associated with a reduced risk of CRC. The stronger chemoprevention of combined use of aspirin and SSRIs is innovative and calls for further studies to confirm the underlying mechanisms and the plausibility of clinical recommendation.
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http://dx.doi.org/10.14309/ajg.0000000000001192DOI Listing
February 2021

Association of mitochondrial DNA copy number with prevalent and incident type 2 diabetes in women: A population-based follow-up study.

Authors:
Ashfaque A Memon Jan Sundquist Anna Hedelius Karolina Palmér Xiao Wang Kristina Sundquist

Sci Rep 2021 Feb 25;11(1):4608. Epub 2021 Feb 25.

Wallenberg Laboratory, Center for Primary Health Care Research, Skåne University Hospital, Lund University/Region Skåne, 6th Floor, Inga Marie Nilsson's gata 53, 20502, Malmö, Sweden.

Mitochondrial dysfunction is an important factor of the aging process and may play a key role in various diseases. Mitochondrial DNA copy number (mtDNA-CN) is an indirect measure of mitochondrial dysfunction and is associated with type 2 diabetes mellitus (T2DM); however, whether mtDNA-CN can predict the risk of developing T2DM is not well-known. We quantified absolute mtDNA-CN in both prevalent and incident T2DM by well-optimized droplet digital PCR (ddPCR) method in a population-based follow-up study of middle aged (50-59 years) Swedish women (n = 2387). The median follow-up period was 17 years. Compared to those who were free of T2DM, mtDNA-CN was significantly lower in both prevalent T2DM and in women who developed T2DM during the follow-up period. Mitochondrial DNA-copy number was also associated with glucose intolerance, systolic blood pressure, smoking status and education. In multivariable Cox regression analysis, lower baseline mtDNA-CN was prospectively associated with a higher risk of T2DM, independent of age, BMI, education, smoking status and physical activity. Moreover, interaction term analysis showed that smoking increased the effect of low mtDNA-CN at baseline on the risk of incident T2DM. Mitochondrial DNA-copy number may be a risk factor of T2DM in women. The clinical usefulness of mtDNA-CN to predict the future risk of T2DM warrants further investigation.
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http://dx.doi.org/10.1038/s41598-021-84132-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7907271PMC
February 2021

Risk-adapted starting age of breast cancer screening in women with a family history of ovarian or other cancers: A nationwide cohort study.

Authors:
Trasias Mukama Elham Kharazmi Kristina Sundquist Jan Sundquist Mahdi Fallah

Cancer 2021 Feb 23. Epub 2021 Feb 23.

Risk Adapted Prevention Group, Division of Preventive Oncology, National Center for Tumor Diseases, German Cancer Research Center, Heidelberg, Germany.

Background: There is a lack of evidence-based recommendations for the age at which women with a family history of cancers other than breast cancer should start breast cancer screening.

Methods: Using Swedish family cancer data sets, the authors conducted a nationwide cohort study including 5,099,172 Swedish women born after 1931 (follow-up, 1958-2015). Accounting for calendar time, they calculated the relative risk of breast cancer for women with a family history of a discordant cancer in 1 first-degree relative. Furthermore, the authors used 10-year cumulative risk to determine the ages at which women with a family history of discordant cancer reached risk thresholds at which women in the general population were recommended to start breast cancer screening.

Results: A family history of cancer at 15 sites was associated with an increased risk of breast cancer. Among women younger than 50 years, the highest risk of breast cancer was observed for those with a family history of ovarian cancer (standardized incidence ratio, 1.44; 95% confidence interval, 1.26-1.64). In these women, the risk of breast cancer associated with a family history at other cancer sites ranged from 1.08-fold for prostate cancer to 1.18-fold for liver cancer. When breast cancer screening was recommended to be started at the age of 50 years for the general population, women with 1 first-degree relative with ovarian cancer attained the threshold risk for screening at the age of 46 years. Women with a family history of other discordant cancers did not reach the risk thresholds for screening at younger ages.

Conclusions: Many cancers showed familial associations with breast cancer, but women with a family history of these cancers (except for ovarian cancer) did not reach risk thresholds for screening at younger ages.
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http://dx.doi.org/10.1002/cncr.33456DOI Listing
February 2021

Beta-blockers use and risk of breast cancer in women with hypertension.

Authors:
Guoqiao Zheng Jan Sundquist Kristina Sundquist Jianguang Ji

Cancer Epidemiol Biomarkers Prev 2021 Feb 22. Epub 2021 Feb 22.

Center for Primary Health Care Research, Lund University.

Background: The risk of breast cancer among hypertensive patients who use beta-blockers has attracted attention. However, the evidence is inconsistent and investigation of the dose-specific associations for subtypes of beta-blockers are limited.

Methods: By incorporating Swedish national registers, breast cancer risk was estimated in women with hypertension who used nonselective beta-blockers and beta-1 selective blockers compared with propensity score-matched non-users. The cumulative defined daily dose was used to study the dose-response association. Test of interaction between beta-blocker use and other antihypertensive medications was performed.

Results: Hypertensive patients taking beta-1 selective blockers (metoprolol, atenolol, bisoprolol) had an increased risk of breast cancer with a hazard ratio (HR) and 95% confidence interval (CI) of 2.39 (1.95-2.94), 2.31 (1.46-3.64), and 3.02 (2.09-4.36), respectively. All of the observed associations were dose-dependent (P trend <0.0001). No significant association was found for the nonselective beta-blocker (propranolol) except that among users of agents acting on the renin-angiotensin system, those who used propranolol had increased breast cancer risk. Modification of agents acting on the renin-angiotensin system on breast cancer risk was also observed for atenolol.

Conclusion: The increased risk of breast cancer associates with the use of beta-1 selective blockers in a dose-response manner.

Impact: Breast cancer surveillance is recommended for hypertensive female patients using beta-1 selective blockers.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-1599DOI Listing
February 2021

Sleep in relation to psychiatric symptoms and perceived stress in Swedish adolescents aged 15 to 19 years.

Authors:
Frida Thorsén Carl Antonson Jan Sundquist Kristina Sundquist

Scand J Child Adolesc Psychiatr Psychol 2020 14;8:10-17. Epub 2020 Feb 14.

Center for Primary Health Care Research, Lund University, Malmö, Sweden.

Background: Sleep affects psychiatric health and perceived stress during adolescence.

Objective: The first aim of this study was to investigate the prevalence of poor sleep in a sample of Swedish adolescents aged 15 to 19 years. The second aim was to investigate correlations between: a) sleep and psychiatric symptoms and; b) sleep and perceived stress. The third aim was to examine possible sex differences in sleep.

Method: In 2011, a total of 185 Swedish adolescents (aged 15 to 19 years) from two upper secondary schools participated in this cross-sectional study. We used three different psychometric scales: Pittsburgh Sleep Quality Index (PSQI), Symptoms Checklist (SCL-90), and Perceived Stress Scale (PSS) to measure sleep, general psychiatric health and perceived stress.

Results: In total, 76% of the female students and 71% of the male students had poor overall sleep quality. A large majority, 93%, reported daytime dysfunction and 60% reported problems staying awake during daily activities. The correlation between sleep and general psychiatric health was 0.44 and the correlation between sleep quality and perceived stress was 0.48. Female students reported significantly more sleep disturbances than male students do.

Conclusions: Three out of four of the upper secondary school students presented with poor overall sleep that associated with psychiatric symptoms and perceived stress. These findings add to results from earlier studies and imply that interventions to improve sleep in adolescents, individually as well as on a societal level, should be considered as one way of trying to impact the observed rising numbers of psychiatric complaints. Such interventions may improve mental and somatic health in adolescents and prevent the development of psychiatric and stress-related symptoms. Further studies of possible methods, and their implementation, for improving sleep in adolescents should be of high priority.
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http://dx.doi.org/10.21307/sjcapp-2020-002DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7685494PMC
February 2020

Huntington's disease among immigrant groups and Swedish-born individuals: a cohort study of all adults 18 years of age and older in Sweden.

Authors:
Per Wändell Sten Fredrikson Axel C Carlsson Xinjun Li Jan Sundquist Kristina Sundquist

Neurol Sci 2021 Jan 30. Epub 2021 Jan 30.

Center for Primary Health Care Research, Lund University, Malmö, Sweden.

Background: There is a lack of studies of Huntington's disease (HD) in immigrants.

Objective: To study the association between country of birth and incident HD in first-generation immigrants versus Swedish-born individuals and in second-generation immigrants versus Swedish-born individuals with Swedish-born parents.

Methods: Study populations included all adults aged 18 years and older in Sweden, i.e., in the first-generation study 6,042,891 individuals with 1034 HD cases and in the second-generation study 4,860,469 individuals with 1001 cases. HD was defined as having at least one registered diagnosis of HD in the National Patient Register. The incidence of HD in different first-generation immigrant groups versus Swedish-born individuals was assessed by Cox regression, expressed as hazard ratios (HRs) and 95% confidence intervals (CI). The models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, and neighborhood socioeconomic status.

Results: Mean age-standardized incidence rates per 100,000 person-years were for all Swedish-born 0.82 and for all foreign born 0.53 and for all men 0.73 and for all women 0.81, with the highest incidence rates for the group 80-84 years of age. After adjusting for potential confounders, the HRs were lower in women in the first- and second-generation, i.e., 0.49 (95% CI 0.36-0.67) and 0.63 (95% 0.45-0.87), respectively, and also among women from Finland or with parents from Finland.

Significance: In general, the risk of HD was lower in first-generation and second-generation immigrant women but not among male immigrants.
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http://dx.doi.org/10.1007/s10072-021-05085-6DOI Listing
January 2021

Huntington's disease among immigrant groups and Swedish-born individuals: a cohort study of all adults 18 years of age and older in Sweden.

Authors:
Per Wändell Sten Fredrikson Axel C Carlsson Xinjun Li Jan Sundquist Kristina Sundquist

Neurol Sci 2021 Jan 30. Epub 2021 Jan 30.

Center for Primary Health Care Research, Lund University, Malmö, Sweden.

Background: There is a lack of studies of Huntington's disease (HD) in immigrants.

Objective: To study the association between country of birth and incident HD in first-generation immigrants versus Swedish-born individuals and in second-generation immigrants versus Swedish-born individuals with Swedish-born parents.

Methods: Study populations included all adults aged 18 years and older in Sweden, i.e., in the first-generation study 6,042,891 individuals with 1034 HD cases and in the second-generation study 4,860,469 individuals with 1001 cases. HD was defined as having at least one registered diagnosis of HD in the National Patient Register. The incidence of HD in different first-generation immigrant groups versus Swedish-born individuals was assessed by Cox regression, expressed as hazard ratios (HRs) and 95% confidence intervals (CI). The models were stratified by sex and adjusted for age, geographical residence in Sweden, educational level, marital status, and neighborhood socioeconomic status.

Results: Mean age-standardized incidence rates per 100,000 person-years were for all Swedish-born 0.82 and for all foreign born 0.53 and for all men 0.73 and for all women 0.81, with the highest incidence rates for the group 80-84 years of age. After adjusting for potential confounders, the HRs were lower in women in the first- and second-generation, i.e., 0.49 (95% CI 0.36-0.67) and 0.63 (95% 0.45-0.87), respectively, and also among women from Finland or with parents from Finland.

Significance: In general, the risk of HD was lower in first-generation and second-generation immigrant women but not among male immigrants.
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http://dx.doi.org/10.1007/s10072-021-05085-6DOI Listing
January 2021

Familial Risks between Pernicious Anemia and Other Autoimmune Diseases in the Population of Sweden.

Authors:
Xinjun Li Hauke Thomsen Kristina Sundquist Jan Sundquist Asta Försti Kari Hemminki

Autoimmune Dis 2021 12;2021:8815297. Epub 2021 Jan 12.

Center for Primary Health Care Research, Lund University, Malmö, Sweden.

Background: Pernicious anemia (PA) is an autoimmune disease (AID) which is caused by lack of vitamin B12 (cobalamin) due to its impaired uptake. PA is a multifactorial disease which is associated with a number of other AID comorbidities and which is manifested as part of autoimmune polyglandular syndrome. Due to the shortage of family studies on PA, we planned to address the problem by assessing familial risks for concordant PA between family members and for discordant PA in families of other AID patients.

Methods: We collected data on patients diagnosed with AIDs from the Swedish hospitals and family data from a population register. We calculated standardized incidence ratios (SIRs) in families for concordant and discordant risks.

Results: The number of PA patients in the offspring generation (for which the familial risk was calculated) was 7701; 278 (3.6%) patients had a family history of PA. The population prevalence of PA was 0.9/1000. The familial risk for PA was 3.88 when any first-degree relative was the proband, equal for men and women. The familial risk was two times higher between siblings than between offspring and parents which may be due to complex genetic background. Associations of PA with 14 discordant AIDs were significant; these included some AIDs that have previously been described as comorbidities in PA patients and several yet unreported associations, including rheumatoid arthritis and other AIDs.

Conclusions: The familial risks for PA were high suggesting multifactorial genetic etiology. The results call for further population-level studies to unravel mechanisms of familial PA which may help to understand the etiology of this disease.
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http://dx.doi.org/10.1155/2021/8815297DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7815416PMC
January 2021

Cervical cancer among Swedish women with drug use disorders: A nationwide epidemiological study.

Authors:
Disa Dahlman Xinjun Li Hedvig Magnusson Jan Sundquist Kristina Sundquist

Gynecol Oncol 2021 Mar 31;160(3):742-747. Epub 2020 Dec 31.

Center for Primary Health Care Research, Department of Clinical Sciences, Lund University/Region Skåne, Malmö, Sweden; Department of Family Medicine and Community Health, Icahn School of Medicine at Mount Sinai, New York, USA; Center for Community-based Healthcare Research and Education (CoHRE), School of Medicine, Shimane University, Japan.

Background/aim: Cervical cancer incidence and mortality has decreased after introduction of national screening in Sweden, but women with drug use disorders (DUD) are less likely to participate in screening programs. We aimed to investigate cervical cancer incidence and mortality among women with DUD compared to the general female population in Sweden.

Methods: We conducted a cohort study based on Swedish national register data for the period January 1997-December 2015. Data was collected for 3,838,248 women aged 15-75 years of whom 50,858 had DUD. Adjusted hazard ratios (HRs) for incident and fatal cervical cancer were calculated for women with and without DUD using Cox regression analysis.

Results: DUD was significantly associated with incident cervical cancer (HR = 1.39, 95% confidence interval [CI] 1.39-1.61), but not fatal cervical cancer (HR = 1.25, 95% CI: 0.91-1.71), after adjusting for age, educational attainment, social welfare, region of residence, marital status and HIV infection.

Conclusion: Women with DUD were thus identified as a risk group for incident cervical cancer, which calls for attention from clinicians and policy makers. It is possible that non-attendance in cancer screening and other healthcare seeking barriers may affect the risk of incident cervical cancer among women with DUD but more research on this topic is needed.
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http://dx.doi.org/10.1016/j.ygyno.2020.12.011DOI Listing
March 2021

The Association between Blood-Based Global DNA Methylation and Venous Thromboembolism.

Authors:
Xiao Wang Ashfaque A Memon Karolina Palmér Peter J Svensson Jan Sundquist Kristina Sundquist

Semin Thromb Hemost 2020 Dec 30. Epub 2020 Dec 30.

Center for Primary Health Care Research, Lund University, Malmö, Sweden.

Alterations in DNA methylation patterns have been associated with many diseases. However, the role of DNA methylation in venous thromboembolism (VTE) is not well established. The aim of this study was to investigate a possible association between global DNA methylation and VTE. The study participants consisted of 168 individuals including 74 patients with primary VTE from the Malmö Thrombophilia Study (MATS) and 94 healthy controls. Among 74 primary VTE patients, 37 suffered VTE recurrence during the follow-up period; 37 nonrecurrent VTE patients were included for comparison. Blood-based global DNA methylation was assessed by an enzyme-linked immunosorbent assay. Global DNA methylation was significantly higher in primary VTE patients compared with the healthy controls (median: 0.17 vs. 0.08%;  < 0.001). After stratification of data from primary VTE patients according to sex, the association between higher global DNA methylation and shorter recurrence-free survival time was of borderline statistical significance in males ( = -0.2;  = 0.052) but not in females ( = 0.02;  = 0.90). Our results show that global DNA methylation is associated with primary VTE and that higher levels of global DNA methylation may be associated with early VTE recurrence in males but not in females. Further investigation on the role of DNA methylation as a diagnostic or preventive biomarker in VTE is warranted.
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http://dx.doi.org/10.1055/s-0040-1722271DOI Listing
December 2020

Time Intervals Under the Lens at Sweden's First Diagnostic Center for Primary Care Patients With Nonspecific Symptoms of Cancer. A Comparison With Matched Control Patients.

Authors:
Jan Sundquist Karolina Palmér Stefan Rydén Charlotta Sävblom Jianguang Ji Emelie Stenman

Front Oncol 2020 30;10:561379. Epub 2020 Nov 30.

Center for Primary Health Care Research, Skåne Regional Council, Lund University, Malmö, Sweden.

Introduction: Fast-track referral pathways for patients with nonspecific, serious symptoms have been implemented in several countries. Our objective was to analyze time intervals in the diagnostic routes of patients diagnosed with cancer at Sweden's first Diagnostic Center (DC) for nonspecific symptoms and compare with time intervals of matched control patients.

Methods: Adult patients with nonspecific symptoms that could not be explained by an initial investigation in primary care were eligible for referral to the DC. Patients diagnosed with cancer were matched with patients at another hospital within the same healthcare organization. We aimed for two control patients per DC-patient and matched on tumor type, age and sex. Five time intervals were compared: 1) patient interval (first symptom-primary care contact), 2) primary care interval (first visit-referral to the DC/secondary care), 3) diagnostic interval (first visit-cancer diagnosis), 4) information interval (cancer diagnosis-patient informed) and 5) treatment interval (cancer diagnosis-treatment start). Comparisons between groups and matched cohort analyses were made.

Results: Sixty-four patients (22.1%) were diagnosed with cancer at the DC, of which eight were not matchable. Forty-two patients were matched with two controls and 14 were matched with one control. There were no significant differences in patient-, primary care-, or diagnostic intervals between the groups. The information interval was shorter at the DC compared to the control group (difference between matched pairs 7 days, p = 0.001) and the treatment interval was also shorter at the DC with significant differences in the matched analysis (difference between matched pairs 13 days, p = 0.049). The findings remained the same in four sensitivity analyses, made to compensate for differences between the groups.

Conclusions: Up to diagnosis, we could not detect significant differences in time intervals between the DC and the control group. However, the shorter information and treatment intervals at the DC should be advantageous for these patients who will get timely access to treatment or palliative care. Due to limitations regarding comparability between the groups, the results must be interpreted with caution and further research is warranted.

Trial Registration: ClinicalTrials.gov-ID: NCT01709539. Registration-date: October 18, 2012.
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http://dx.doi.org/10.3389/fonc.2020.561379DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7735559PMC
November 2020

Attention deficit hyperactivity disorder in first- and second-generation immigrant children and adolescents: A nationwide cohort study in Sweden.

Authors:
Mehdi Osooli Henrik Ohlsson Jan Sundquist Kristina Sundquist

J Psychosom Res 2021 Feb 9;141:110330. Epub 2020 Dec 9.

Center for Primary Health Care Research, Lund University, Malmö, Sweden; Department of Family Medicine and Community Health, Department of Population Health Science and Policy, Icahn School of Medicine at Mount Sinai, New York, USA; Department of Functional Pathology, Center for Community-based Healthcare Research and Education (CoHRE), School of Medicine, Shimane University, Shimane, Japan.

Background: Studies on the incidence of Attention Deficit Hyperactivity Disorder (ADHD) among immigrant children and adolescents is limited and results are mixed. The aim of this study was to compare the ADHD risk between first- and second-generation immigrants aged 4-16 years and their native peers in Sweden.

Methods: This was an open nationwide retrospective cohort study. We included 1,902,526 native and 805,450 children and adolescents with an immigrant background, born 1987-2010, and aged 4-16 years at baseline. We identified participants using national population data and participants were observed until they received an ADHD diagnosis in the National Patient Register, turned 18 years, migrated, died, or until the end of the study, whichever came first. ADHD risks were adjusted for birth year and age and maternal income at baseline.

Results: For both males and females, the ADHD risk was lower among most immigrant groups. However, the combination of a Swedish-born mother and foreign-born father was associated with an increased risk of ADHD. The ADHD risk varied substantially between immigrants from different regions of the world. For example, immigrants from other Scandinavian countries, North America, and Latin America and the Caribbean had higher rates of ADHD compared with natives.

Conclusions: Future research should examine the underlying factors behind the differences in ADHD risks between certain immigrant subgroups and natives, such as family structure, cultural and language barriers and potential differences in health care utilization among immigrant families.
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http://dx.doi.org/10.1016/j.jpsychores.2020.110330DOI Listing
February 2021

Does Neighborhood Alcohol Availability Moderate the Impact of Familial Liability and Marital Status on Risk for Alcohol Use Disorders? A Swedish National Study.

Authors:
Kenneth S Kendler Sara Larsson Lönn Katherine J Karriker-Jaffe Jessica E Salvatore Jan Sundquist Kristina Sundquist

J Stud Alcohol Drugs 2020 Nov;81(6):816-823

Center for Primary Health Care Research, Lund University, Malmö, Sweden.

Objective: The purpose of this study was to determine whether ease of access to alcohol at the neighborhood level moderates the impact of familial liability and marital status on risk for alcohol use disorder (AUD).

Method: Individuals in Sweden were divided into those residing in a neighborhood with (n = 14.1%) versus without (n = 85.9%) an alcohol outlet (bars/nightclubs or government stores). AUD was detected through national medical, legal, and pharmacy registries. Using an additive model predicting AUD registration over 5 years in 1,624,814 individuals, we tested for interactions between the presence of outlets in the individuals' neighborhoods and familial risk for externalizing syndromes and marital status.

Results: In both males and females, we found positive and significant interactions in the prediction of AUD between the presence versus absence of a nearby alcohol outlet with (a) familial risk and (b) single and divorced versus married status. Similar but nonsignificant interactions were seen between nearby outlets and widowed versus married status. These results changed little when all cases with prior AUD were removed from the sample. For males, most of the interaction arose from the proximity of bars/nightclubs, whereas for females the results varied across different kinds of outlets.

Conclusions: Environments that provide easy access to alcohol augment the impact of a range of risk factors for AUD, especially familial vulnerability and the reduced social constraints associated with single, divorced, and widowed marital status.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7754851PMC
November 2020

Familial risks between giant cell arteritis and Takayasu arteritis and other autoimmune diseases in the population of Sweden.

Authors:
Hauke Thomsen Xinjun Li Kristina Sundquist Jan Sundquist Asta Försti Kari Hemminki

Sci Rep 2020 11 30;10(1):20887. Epub 2020 Nov 30.

Division of Molecular Genetic Epidemiology, German Cancer Research Centre (DKFZ), 69120, Heidelberg, Germany.

Giant cell arteritis (GCA, also called temporal arteritis) is a rare and Takayasu arteritis (TA) is an even rarer autoimmune disease (AID), both of which present with inflammatory vasculitis of large and medium size arteries. The risk factors are largely undefined but disease susceptibility has been associated with human leukocyte antigen locus. Population-level familial risk is not known. In the present nation-wide study we describe familial risk for GCA and for GCA and TA with any other AID based on the Swedish hospital diagnoses up to years 2012. Family relationships were obtained from the Multigeneration Register. Familial standardized incidence ratios (SIRs) were calculated for offspring whose parents or siblings were diagnosed with GCA, TA or any other AID. The number of GCA patients in the offspring generation was 4695, compared to 209 TA patients; for both, familial patients accounted for 1% of all patients. The familial risk for GCA was 2.14, 2.40 for women and non-significant for men. GCA was associated with 10 other AIDs and TA was associated with 6 other AIDs; both shared associations with polymyalgia rheumatica and rheumatoid arthritis. The results showed that family history is a risk factor for GCA. Significant familial associations of both GCA and TA with such a number of other AIDs provide evidence for polyautoimmunity among these diseases.
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http://dx.doi.org/10.1038/s41598-020-77857-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7705754PMC
November 2020

Familial associations for rheumatoid autoimmune diseases.

Authors:
Hauke Thomsen Xinjun Li Kristina Sundquist Jan Sundquist Asta Försti Kari Hemminki

Rheumatol Adv Pract 2020 22;4(2):rkaa048. Epub 2020 Sep 22.

Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Objective: Previous studies have shown a familial component in RA and in some other rheumatic autoimmune diseases (RAIDs), but because of the different study designs the risk estimates for familial risks differ extensively. The objective of this study is to identify familial components for RAIDs.

Methods: We collected data on patients diagnosed in Swedish hospitals with RA, AS, PM/DM, SS, SLE and SSc (and scleroderma) and calculated familial standardized incidence ratios (SIRs) for each of these (concordant) and between them (discordant).

Results: The combined number of RAID patients in the offspring population (for whom SIRs were calculated) was 71 544, and in the whole population the number was 152 714, accounting for 19.8% of all autoimmune diseases in Sweden. AS showed the highest concordant familial risk of 18.42, followed by SLE (14.04), SS (8.63), SSc (4.50), PM/DM (4.03) and RA (3.03). There was no sex difference in SIRs. Risks for AS and SLE were 80.28 and 19.53 for persons whose parents and siblings were affected. Discordant risks were far lower than concordant risks, but they were significant for RA with all the other five RAIDs, for SLE and SSc with four RAIDs, for AS and SS with three RAIDs and for PM/DM with two RAIDs, attesting to extensive polyautoimmunity between RAIDs.

Conclusion: The derived familial risks in this nationwide family study on medically diagnosed RAID are compatible with emerging evidence on the polygenic background of these complex diseases. Novel genetic pathways offer new therapeutic targets that alleviate disease onset optimally in high-risk familial patients and others.
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http://dx.doi.org/10.1093/rap/rkaa048DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7673201PMC
September 2020

Risk of somatic diseases in offspring of survivors with childhood or adolescent central nervous system tumor in Sweden.

Authors:
Wuqing Huang Kristina Sundquist Jan Sundquist Jianguang Ji

Int J Cancer 2020 Nov 13. Epub 2020 Nov 13.

Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden.

With the improvement of treatments, a growing number of survivors with childhood or adolescent central nervous system (CNS) tumor are parenting their own children. We aimed to explore the risk of somatic diseases among children of these survivors compared to population controls. Children of survivors with CNS tumor below age of 20 were identified between 1973 and 2014 by combining the several Swedish registers. Five children without parental CNS tumor were matched randomly to generate the population comparisons. Relative risk (RR) and absolute excess risk (AER) were calculated for overall somatic diseases, and hazard ratio (HR) was calculated for specific type of somatic diseases. A total of 2231 somatic disease diagnoses were identified in children of survivors with a cumulative incidence rate of 94.77 per 1000 person-years, whereas the rate was 92.79 in matched comparisons thus resulting in an overall RR of 1.02 (95% CI = 0.98-1.07) and AER of 1.98 (95% CI = -2.06, 6.13). Specifically, five of 1364 children of survivors had CNS tumor with an incidence rate of 0.21 per 1000 person-year, whereas the rate was 0.04 in children of matched children, generating a HR of 4.91 (95% CI = 1.42-16.96). Children of male survivors were at a statistically increased risk of malignancy, as well as infectious and parasitic diseases. In conclusion, no significantly higher risk of overall somatic diseases was found in children of survivors with CNS tumor before the age of 20, but children with a paternal diagnosis of CNS tumor had significantly increased risk of malignancies and infectious and parasitic diseases.
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http://dx.doi.org/10.1002/ijc.33394DOI Listing
November 2020

Risk of colorectal cancer in patients with diabetes mellitus: A Swedish nationwide cohort study.

Authors:
Uzair Ali Khan Mahdi Fallah Kristina Sundquist Jan Sundquist Hermann Brenner Elham Kharazmi

PLoS Med 2020 11 13;17(11):e1003431. Epub 2020 Nov 13.

Division of Preventive Oncology, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Heidelberg, Germany.

Background: Colorectal cancer (CRC) incidence is increasing among young adults below screening age, despite the effectiveness of screening in older populations. Individuals with diabetes mellitus are at increased risk of early-onset CRC. We aimed to determine how many years earlier than the general population patients with diabetes with/without family history of CRC reach the threshold risk at which CRC screening is recommended to the general population.

Methods And Findings: A nationwide cohort study (follow-up:1964-2015) involving all Swedish residents born after 1931 and their parents was carried out using record linkage of Swedish Population Register, Cancer Registry, National Patient Register, and Multi-Generation Register. Of 12,614,256 individuals who were followed between 1964 and 2015 (51% men; age range at baseline 0-107 years), 162,226 developed CRC, and 559,375 developed diabetes. Age-specific 10-year cumulative risk curves were used to draw conclusions about how many years earlier patients with diabetes reach the 10-year cumulative risks of CRC in 50-year-old men and women (most common age of first screening), which were 0.44% and 0.41%, respectively. Diabetic patients attained the screening level of CRC risk earlier than the general Swedish population. Men with diabetes reached 0.44% risk at age 45 (5 years earlier than the recommended age of screening). In women with diabetes, the risk advancement was 4 years. Risk was more pronounced for those with additional family history of CRC (12-21 years earlier depending on sex and benchmark starting age of screening). The study limitations include lack of detailed information on diabetes type, lifestyle factors, and colonoscopy data.

Conclusions: Using high-quality registers, this study is, to our knowledge, the first one that provides novel evidence-based information for risk-adapted starting ages of CRC screening for patients with diabetes, who are at higher risk of early-onset CRC than the general population.
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http://dx.doi.org/10.1371/journal.pmed.1003431DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7665813PMC
November 2020

Drug use disorder and risk of incident and fatal breast cancer: a nationwide epidemiological study.

Authors:
Disa Dahlman Hedvig Magnusson Xinjun Li Jan Sundquist Kristina Sundquist

Breast Cancer Res Treat 2021 Feb 6;186(1):199-207. Epub 2020 Nov 6.

Center for Primary Health Care Research, Department of Clinical Sciences, Lund University/Region Skåne, Box 503 22, Malmö, Sweden.

Purpose: Breast cancer is one of the most common cancer forms in women and it is often detected by screening. However, women with drug use disorders (DUD) are less likely to be reached by screening programs. In this study, we aimed to investigate breast cancer incidence, mortality and stage at time of diagnosis among women with DUD compared to the general female population in Sweden.

Methods: We performed a follow-up study based on Swedish national register data for the period January 1997-December 2015. The study was based on 3,838,248 women aged 15-75 years, of whom 50,858 were registered with DUD. Adjusted hazard ratios (HRs) for incident and fatal breast cancer, and cancer stage at time of diagnosis, were calculated for women with and without DUD using Cox regression analysis.

Results: DUD was associated with incident breast cancer (HR 1.08, 95% confidence interval [CI] 1.02-1.14, p = 0.0069), fatal breast cancer (HR 1.60, 95% CI 1.42-1.82, p < 0.001), and stage IV breast cancer, i.e. metastasis at diagnosis (HR 2.06, 95% CI 1.44-2.95, p < 0.001).

Conclusions: Women with DUD were identified as a risk group for incident, fatal and metastasized breast cancer, which calls for attention from clinicians and policy makers. Cancer screening attendance and other healthcare seeking barriers are likely to affect the risk increase among women who use drugs; however, more research is needed on the underlying mechanisms.
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http://dx.doi.org/10.1007/s10549-020-05998-4DOI Listing
February 2021

Risk of invasive breast cancer in relatives of patients with breast carcinoma in situ: a prospective cohort study.

Authors:
Trasias Mukama Mahdi Fallah Hermann Brenner Xing Xu Kristina Sundquist Jan Sundquist Elham Kharazmi

BMC Med 2020 11 5;18(1):295. Epub 2020 Nov 5.

Division of Preventive Oncology, Risk Adapted Prevention (RAD) Group, German Cancer Research Center (DKFZ) and National Center for Tumor Diseases (NCT), Im Neuenheimer Feld 581, 69120, Heidelberg, Germany.

Background: Wide implementation of mammography screening has resulted in increased numbers of women diagnosed with breast carcinoma in situ. We aimed to determine the risk of invasive breast cancer in relatives of patients with breast carcinoma in situ in comparison to the risk in relatives of patients with invasive breast cancer.

Methods: We analyzed the occurrence of cancer in a nationwide cohort including all 5,099,172 Swedish women born after 1931 with at least one known first-degree relative. This was a record linkage study of Swedish family cancer datasets, including cancer registry data collected from January 1, 1958, to December 31, 2015. We calculated standardized incidence ratios (SIRs) and 10-year cumulative risk of breast cancer diagnosis for women with a family history of in situ and invasive breast cancer.

Results: Having one first-degree relative with breast carcinoma in situ was associated with 50% increased risk of invasive breast cancer (SIR = 1.5, 95% CI 1.4-1.7) when compared to those who had no family history of invasive breast cancer or breast carcinoma in situ in either first- or second-degree relatives. Similarly, having one first-degree relative with invasive breast cancer was associated with 70% (1.7, 1.7-1.8) increased risk. The 10-year cumulative risk for women at age 50 with a relative with breast carcinoma in situ was 3.5% (2.9-3.9%) and was not significantly different from 3.7% (3.6-3.8%) risk for 50-year-old women with a relative with invasive breast cancer (95% confidence intervals overlapped).

Conclusions: The risk of invasive breast cancer for women with a family history of breast carcinoma in situ was comparable to that for women with a family history of invasive breast cancer. Therefore, family history of breast carcinoma in situ should not be overlooked in recommendations for breast cancer prevention for women with a family history of breast cancer.
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http://dx.doi.org/10.1186/s12916-020-01772-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643418PMC
November 2020

Psychiatric disorders in offspring of childhood or adolescent central nervous system tumor survivors: a national cohort study.

Authors:
Wuqing Huang Kristina Sundquist Jan Sundquist Jianguang Ji

Cancer Med 2021 Jan 1;10(2):675-683. Epub 2020 Nov 1.

Center for Primary Health Care Research, Lund University/Region Skåne, Lund, Sweden.

Background: Children experience a higher risk of psychiatric problems when their parents are diagnosed with cancer. However, the psychological effect among offspring who are born after parental cancer diagnosed in childhood or adolescence is unknown. We aimed to investigate the risk of psychiatric disorders in children of survivors with childhood or adolescent central nervous system (CNS) tumors.

Methods: By combining several nationwide Swedish registers, we identified all children who had at least one parent previously diagnosed with CNS tumor below the age of 20. Five children without parental CNS tumor were randomly selected for the matching. Cox proportional hazards model was used to calculate hazard ratios (HRs) with 95% confidence interval (CI).

Results: The incidence rate of psychiatric disorders was 8.46 per 1000 person-years in children of CNS tumor survivors, whereas the rate was 7.47 in the matched comparisons, yielding an adjusted HR of 1.10 (95% CI = 0.94, 1.28). Boys of survivors had a higher risk of psychiatric disorders (adjusted HR = 1.29, 95% CI = 1.04, 1.59). The risk of the specific types of psychiatric disorders in children of tumor survivors was comparable with that in the matched comparisons, except for mental retardation. Children of survivors experienced 2.36 times higher risk of mental retardation (95% CI = 1.21, 4.58), mainly of mild mental retardation (adjusted HR = 2.99, 95% CI = 1.40, 6.38).

Conclusion: Children of survivors with CNS tumor in early life did not experience a significantly increased risk of overall psychiatric disorders, with the exception of an elevated risk of mental retardation that was mainly mild.
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http://dx.doi.org/10.1002/cam4.3591DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7877351PMC
January 2021

Familial associations for Addison's disease and between Addison's disease and other autoimmune diseases.

Authors:
Hauke Thomsen Xinjun Li Kristina Sundquist Jan Sundquist Asta Försti Kari Hemminki

Endocr Connect 2020 Nov;9(11):1114-1120

Division of Molecular Genetic Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.

Design: Addison's disease (AD) is a rare autoimmune disease (AID) of the adrenal cortex, present as an isolated AD or part of autoimmune polyendocrine syndromes (APSs) 1 and 2. Although AD patients present with a number of AID co-morbidities, population-based family studies are scarce, and we aimed to carry out an unbiased study on AD and related AIDs.

Methods: We collected data on patients diagnosed with AIDs in Swedish hospitals and calculated standardized incidence ratios (SIRs) in families for concordant AD and for other AIDs, the latter as discordant relative risks.

Results: The number of AD patients was 2852, which accounted for 0.4% of all hospitalized AIDs. A total of 62 persons (3.6%) were diagnosed with familial AD. The SIR for siblings was remarkably high, reaching 909 for singleton siblings diagnosed before age 10 years. It was 32 in those diagnosed past age 29 years and the risk for twins was 323. SIR was 9.44 for offspring of affected parents. AD was associated with 11 other AIDs, including thyroid AIDs and type 1 diabetes and some rarer AIDs such as Guillain-Barre syndrome, myasthenia gravis, polymyalgia rheumatica and Sjögren's syndrome.

Conclusions: The familial risk for AD was very high implicating genetic etiology, which for juvenile siblings may be ascribed to APS-1. The adult part of sibling risk was probably contributed by recessive polygenic inheritance. AD was associated with many common AIDs; some of these were known co-morbidities in AD patients while some other appeared to more specific for a familial setting.
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http://dx.doi.org/10.1530/EC-20-0328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774767PMC
November 2020

Familial associations for Addison's disease and between Addison's disease and other autoimmune diseases.

Authors:
Hauke Thomsen Xinjun Li Kristina Sundquist Jan Sundquist Asta Försti Kari Hemminki

Endocr Connect 2020 Nov;9(11):1114-1120

Division of Molecular Genetic Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.

Design: Addison's disease (AD) is a rare autoimmune disease (AID) of the adrenal cortex, present as an isolated AD or part of autoimmune polyendocrine syndromes (APSs) 1 and 2. Although AD patients present with a number of AID co-morbidities, population-based family studies are scarce, and we aimed to carry out an unbiased study on AD and related AIDs.

Methods: We collected data on patients diagnosed with AIDs in Swedish hospitals and calculated standardized incidence ratios (SIRs) in families for concordant AD and for other AIDs, the latter as discordant relative risks.

Results: The number of AD patients was 2852, which accounted for 0.4% of all hospitalized AIDs. A total of 62 persons (3.6%) were diagnosed with familial AD. The SIR for siblings was remarkably high, reaching 909 for singleton siblings diagnosed before age 10 years. It was 32 in those diagnosed past age 29 years and the risk for twins was 323. SIR was 9.44 for offspring of affected parents. AD was associated with 11 other AIDs, including thyroid AIDs and type 1 diabetes and some rarer AIDs such as Guillain-Barre syndrome, myasthenia gravis, polymyalgia rheumatica and Sjögren's syndrome.

Conclusions: The familial risk for AD was very high implicating genetic etiology, which for juvenile siblings may be ascribed to APS-1. The adult part of sibling risk was probably contributed by recessive polygenic inheritance. AD was associated with many common AIDs; some of these were known co-morbidities in AD patients while some other appeared to more specific for a familial setting.
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http://dx.doi.org/10.1530/EC-20-0328DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7774767PMC
November 2020

Familial associations between autoimmune hepatitis and primary biliary cholangitis and other autoimmune diseases.

Authors:
Hauke Thomsen Xinjun Li Kristina Sundquist Jan Sundquist Asta Försti Kari Hemminki

PLoS One 2020 20;15(10):e0240794. Epub 2020 Oct 20.

Division of Molecular Genetic Epidemiology, German Cancer Research Centre (DKFZ), Heidelberg, Germany.

Autoimmune hepatitis (AH) and primary biliary cirrhosis (PBC) are autoimmune diseases (AIDs) targeting cellular components of the liver. Being rare diseases, limited data are available about familial risks among these AIDs (concordant) or between them and other AIDs (discordant). We aimed to carry out an unbiased study on these AIDs based on medically diagnosed patients. We collected data on patients diagnosed in Swedish hospitals with AH, PBC and other AIDs and calculated familial standardized incidence ratios (SIRs) for concordant and discordant familial relative risks. The number of AH patients was 6,269, of whom 43.0% were male; patient numbers for PBC were 4,269, with 17.8% males. AH accounted for 0.8% and 0.6% of all hospitalized AIDs in Sweden. For AH only the familial risk between siblings was significant (3.83). For PBC the risks for offspring of parents (9.05) and siblings (10.88) were high, but only risk for females was significant. Spousal risks were very high, 5.91 and 6.07 for AH. Risk for AH was 2.21 in families of PBC, and it was 2.47 for PBC in families of AH patients. Among other AIDs, 14 showed a significant association with AH, compared to 16 AIDs with PBC. The surprising finding in this nation-wide family study on medically diagnosed patients was the high risk for AH (6.0) between spouses, which exceed the risk between siblings, suggesting the existence of strong environmental risk factors. AH and PBC were associated with multiple other AIDs. The results call attention to environmental factors in AID etiology which should also be in focus in taking anamnestic data from patients.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0240794PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7575086PMC
December 2020

Diagnostic potential of circulating cell-free nuclear and mitochondrial DNA for several cancer types and nonmalignant diseases: A study on suspected cancer patients.

Authors:
Kristina Sundquist Jan Sundquist Anna Hedelius Ashfaque A Memon

Mol Carcinog 2020 12 13;59(12):1362-1370. Epub 2020 Oct 13.

Center for Primary Health Care Research, Lund University, Malmö, Sweden.

Circulating cell-free nuclear DNA (nDNA) has been implicated in individual cancer types with a diagnostic value; however, the role of cell-free mitochondrial DNA (mtDNA) in cancers is controversial. We aimed to investigate and compare the diagnostic potential of both nDNA and mtDNA for multiple cancers and to investigate their ability to distinguish multiple cancers from healthy controls and from nonmalignant diseases. We also investigated the prognostic value of both nDNA and mtDNA. The absolute copy number of circulating DNAs in suspected cancer patients (n = 286) referred to a cancer diagnostic center and healthy controls (n = 109) was quantified by droplet digital polymerase chain reaction. Among the suspected cancer patients, 66 (23%) were diagnosed with various cancers, 193 (67%) with nonmalignant diseases, and 27 (10%) with no active disease. Levels of nDNA were significantly higher in cancers (copies/μl; mean ± SD, 21.0 ± 14.2) as compared with nonmalignant diseases (15.2 ± 10.0) and controls (9.3 ± 4.1). In contrast, levels of mtDNA were significantly lower in cancers (copies/μl; mean ± SD, 68,557 ± 66,663) and nonmalignant diseases (60,174 ± 55,831) as compared with controls (98,714 ± 77,789). Receiver operating curve analysis showed that nDNA not only could distinguish multiple cancers from controls (area under curve [AUC] = 0.78; 95% confidence interval [CI] = 0.70-0.86) but also from nonmalignant diseases (AUC = 0.68; 95% CI = 0.59-0.76). However, mtDNA could only differentiate cancers from controls (AUC = 0.65; 95% CI = 0.56-0.73). Higher levels of nDNA were also associated with increased mortality in the cancer patients (hazard ratio = 2.3; 95% CI = 1.1-4.7). Circulating cell-free nDNA, but not the mtDNA, could distinguish multiple cancers from nonmalignant diseases and was associated with poor survival of cancer patients.
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http://dx.doi.org/10.1002/mc.23261DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7702094PMC
December 2020

Association of post-diagnostic use of cholera vaccine with survival outcome in breast cancer patients.

Authors:
Guoqiao Zheng Jan Sundquist Kristina Sundquist Jianguang Ji

Br J Cancer 2021 Jan 7;124(2):506-512. Epub 2020 Oct 7.

Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden.

Background: Expensive cancer treatment calls for alternative ways such as drug repurposing to develop effective drugs. The aim of this study was to analyse the effect of post-diagnostic use of cholera vaccine on survival outcome in breast cancer patients.

Methods: Cancer diagnosis and cholera vaccination were obtained by linkage of several Swedish national registries. One vaccinated patient was matched with maximum two unvaccinated individuals based on demographic, clinical and socioeconomic factors. We performed proportional Cox regression model to analyse the differences in overall and disease-specific survivals between the matched patients.

Results: In total, 617 patients received cholera vaccine after breast cancer diagnosis. The median (interquartile range) time from diagnosis to vaccination was 30 (15-51) months and from vaccination to the end of follow-up it was 62 (47-85) months. Among them, 603 patients were matched with 1194 unvaccinated patients. Vaccinated patients showed favourable overall survival (hazard ratio (HR): 0.54, 95% confidence interval (CI): 0.37-0.79) and disease-specific survival (HR: 0.53, 95% CI: 0.33-0.84), compared to their unvaccinated counterpart. The results were still significant in multiple sensitivity analyses.

Conclusions: Post-diagnostic use of cholera vaccine is associated with a favourable survival rate in breast cancer patients; this provides evidence for repurposing it against breast cancer.
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http://dx.doi.org/10.1038/s41416-020-01108-9DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7852596PMC
January 2021

Rate differences between first and second primary cancers may outline immune dysfunction as a key risk factor.

Authors:
Guoqiao Zheng Kristina Sundquist Jan Sundquist Asta Försti Akseli Hemminki Kari Hemminki

Cancer Med 2020 Nov 22;9(21):8258-8265. Epub 2020 Sep 22.

Division of Molecular Genetic Epidemiology, German Cancer Research Center (DKFZ), Heidelberg, Germany.

Background: Many cancers are increased in immunosuppressed patients and evidence is accumulating that immune dysfunction may be a contributing risk factor for second primary cancers (SPCs). The aim of this study was to explore the potential influence of immune mechanisms in SPC.

Methods: We used the Swedish Cancer Registry (1990-2015) to select 13 male and 14 female first primary cancers (FPCs) that are known to be related to immune suppression. We assessed relative risks (RRs) for any of these as concordant (same first and second cancer) and discordant FPC-SPC pairs. Hierarchical clustering of significant RRs was performed for cancers as FPC and SPC.

Results: Concordant risks for SPCs were excessive in men and women for nasal (RRs 59.3 for men and 150.6 for women), tongue/mouth (51.7 and 100.8), and lip (32.4 and 61.2) cancers. Heatmaps showed that some cancers, such as skin cancer, tongue/mouth cancers, and non-Hodgkin lymphoma had multiple bidirectional associations as FPC and SPC. Nasal cancer and chronic lymphocytic leukemia had associations mainly as FPC while liver and kidney cancers showed most associations as SPC.

Conclusions: Immune dysfunction may be a plausible contributing factor for most of the associations, which calls for experimental verification.
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http://dx.doi.org/10.1002/cam4.3454DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7643639PMC
November 2020

Early-Life Cardiorespiratory Fitness and Long-term Risk of Prostate Cancer.

Authors:
Casey Crump Pär Stattin James D Brooks Tanja Stocks Jan Sundquist Weiva Sieh Kristina Sundquist

Cancer Epidemiol Biomarkers Prev 2020 Nov 20;29(11):2187-2194. Epub 2020 Aug 20.

Department of Family Medicine and Community Health, Icahn School of Medicine at Mount Sinai, New York, New York.

Background: Adolescence is a period of rapid prostatic growth, yet is understudied for susceptibility for future risk of prostate cancer. We examined cardiorespiratory fitness (CRF) in late adolescence in relation to long-term prostate cancer risk.

Methods: A population-based cohort study was conducted of all 699,125 Swedish military conscripts during 1972-1985 (97%-98% of 18-year-old men) in relation to risk of prostate cancer overall, aggressive prostate cancer, and prostate cancer mortality during 1998-2017 (ages 50-65 years). CRF was measured by maximal aerobic workload, and prostate cancer was ascertained using the National Prostate Cancer Register. Muscle strength was examined as a secondary predictor.

Results: In 38.8 million person-years of follow-up, 10,782 (1.5%) men were diagnosed with prostate cancer. Adjusting for sociodemographic factors, height, weight, and family history of prostate cancer, high CRF was associated with a slightly increased risk of any prostate cancer [highest vs. lowest quintile: incidence rate ratio (IRR), 1.10; 95% CI, 1.03-1.19; = 0.008], but was neither significantly associated with aggressive prostate cancer (1.01; 0.85-1.21; = 0.90) nor prostate cancer mortality (1.24; 0.73-2.13; = 0.42). High muscle strength also was associated with a modestly increased risk of any prostate cancer (highest vs. lowest quintile: IRR, 1.14; 95% CI, 1.07-1.23; < 0.001), but neither with aggressive prostate cancer (0.88; 0.74-1.04; = 0.14) nor prostate cancer mortality (0.81; 0.48-1.37; = 0.43).

Conclusions: High CRF or muscle strength in late adolescence was associated with slightly increased future risk of prostate cancer, possibly related to increased screening, but neither with risk of aggressive prostate cancer nor prostate cancer mortality.

Impact: These findings illustrate the importance of distinguishing aggressive from indolent prostate cancer and assessing for potential detection bias.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642066PMC
November 2020

Early-Life Cardiorespiratory Fitness and Long-term Risk of Prostate Cancer.

Authors:
Casey Crump Pär Stattin James D Brooks Tanja Stocks Jan Sundquist Weiva Sieh Kristina Sundquist

Cancer Epidemiol Biomarkers Prev 2020 Nov 20;29(11):2187-2194. Epub 2020 Aug 20.

Department of Family Medicine and Community Health, Icahn School of Medicine at Mount Sinai, New York, New York.

Background: Adolescence is a period of rapid prostatic growth, yet is understudied for susceptibility for future risk of prostate cancer. We examined cardiorespiratory fitness (CRF) in late adolescence in relation to long-term prostate cancer risk.

Methods: A population-based cohort study was conducted of all 699,125 Swedish military conscripts during 1972-1985 (97%-98% of 18-year-old men) in relation to risk of prostate cancer overall, aggressive prostate cancer, and prostate cancer mortality during 1998-2017 (ages 50-65 years). CRF was measured by maximal aerobic workload, and prostate cancer was ascertained using the National Prostate Cancer Register. Muscle strength was examined as a secondary predictor.

Results: In 38.8 million person-years of follow-up, 10,782 (1.5%) men were diagnosed with prostate cancer. Adjusting for sociodemographic factors, height, weight, and family history of prostate cancer, high CRF was associated with a slightly increased risk of any prostate cancer [highest vs. lowest quintile: incidence rate ratio (IRR), 1.10; 95% CI, 1.03-1.19; = 0.008], but was neither significantly associated with aggressive prostate cancer (1.01; 0.85-1.21; = 0.90) nor prostate cancer mortality (1.24; 0.73-2.13; = 0.42). High muscle strength also was associated with a modestly increased risk of any prostate cancer (highest vs. lowest quintile: IRR, 1.14; 95% CI, 1.07-1.23; < 0.001), but neither with aggressive prostate cancer (0.88; 0.74-1.04; = 0.14) nor prostate cancer mortality (0.81; 0.48-1.37; = 0.43).

Conclusions: High CRF or muscle strength in late adolescence was associated with slightly increased future risk of prostate cancer, possibly related to increased screening, but neither with risk of aggressive prostate cancer nor prostate cancer mortality.

Impact: These findings illustrate the importance of distinguishing aggressive from indolent prostate cancer and assessing for potential detection bias.
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http://dx.doi.org/10.1158/1055-9965.EPI-20-0535DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7642066PMC
November 2020

Risk of Being Born Preterm in Offspring of Cancer Survivors: A National Cohort Study.

Authors:
Wuqing Huang Kristina Sundquist Jan Sundquist Jianguang Ji

Front Oncol 2020 4;10:1352. Epub 2020 Aug 4.

Center for Primary Health Care Research, Lund University/Region Skåne, Malmö, Sweden.

With the increased number of cancer survivors, it is necessary to explore the effect of cancer and its treatments on pregnancy outcomes, such as preterm birth, which seriously endangers the health of offspring. We aimed to explore the risk of being born preterm among offspring of cancer survivors. This is a retrospective cohort study. All singleton live births between 1973 and 2014 in Sweden with information of birth outcomes were retrieved from the Swedish Medical Birth Register. By linking to several Swedish registers, we identified all parents of children and parental cancer diagnosis. Logistic regression was used to estimate odds ratios and 95% confidence intervals. As compared to the children without parental cancer, the risk of being born preterm was significantly higher among children of overall female cancer survivors born after cancer diagnosis with an adjusted OR of 1.48 (95 CI% = 1.39-1.59), in particular those diagnosed with childhood cancer and cancer in female genital organs. Besides, the risk might continuously decline with time at the first 8 years after maternal diagnosis. A higher risk of being born preterm was found among offspring of male survivors diagnosed with central nervous system cancer (Adjusted = 1.26, 95% CI = 1.04-1.53). Our study provides evidence for a higher risk of being born preterm among children of female cancer survivors and male survivors with central nervous system tumor, as well as indicates that the effect on female reproductive system from cancer and related-treatments might decline with time.
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http://dx.doi.org/10.3389/fonc.2020.01352DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7418466PMC
August 2020

Evidence for a Causal Relationship Between Academic Achievement and Cigarette Smoking.

Authors:
Kenneth S Kendler Henrik Ohlsson Abigail A Fagan Paul Lichtenstein Jan Sundquist Kristina Sundquist

Nicotine Tob Res 2021 01;23(2):334-340

Center for Primary Health Care Research, Lund University, Malmö, Sweden.

Introduction: Academic achievement (AA) is associated with smoking rates. Can we determine the degree to which this relationship is likely a causal one?

Methods: We predict smoking in male conscripts (mean age 18.2) assessed from 1984 to 1991 (N = 233 248) and pregnant females (mean age 27.7) receiving prenatal care 1972-1990 (N = 494 995) from AA assessed in all students at 16. Instrumental variable (IV) analyses used the instrument month-of-birth as in each school year, older children have high AA. Co-relative analyses used AA-smoking associations in the population, cousins and siblings to predict the AA-smoking relationship in MZ twins, thereby controlling for familial confounding.

Results: In males, higher AA was associated with a substantial decrease in risk for smoking (odds ratio [OR] [95% confidence intervals [CIs]] per standard deviation [SD] = 0.41 [0.40-0.41]) while the parallel figures obtain from our IV and co-relative analyses were 0.47 (0.39-0.57) and 0.51 (0.43-0.60), respectively. In females, these figures for pre-pregnancy smoking were, respectively, 0.39 (0.39-0.39), 0.50 (0.46-0.54) and 0.54 (0.51-0.58). Results for heavy versus light smoking suggested a causal effect but were inconsistent across methods. However, among females smoking prior to pregnancy, AA predicted a reduced risk for continued smoking with ORs for uncontrolled, IV, and co-relative analyses equaling, respectively, were 0.54 (0.53-0.55) 0.68 (0.56-0.82) and 0.78 (0.66-0.91), respectively.

Conclusions: Two different methods produced consistent evidence that higher AA has a causal effect on reducing smoking rates and increasing cessation rates in smoking pregnant females. Improving AA may result in meaningful gains in population health through reduced smoking.

Implications: This study provides consistent evidence across two different methods that high AA is causally related to reduced rates of smoking and increasing rates of smoking cessation among pregnant women. Our results suggest that interventions that improve educational achievement in adolescence would reduce tobacco consumption, thereby improving public health.
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http://dx.doi.org/10.1093/ntr/ntaa161DOI Listing
January 2021