Prenatal nitrosatable prescription drug intake, drinking water nitrate, and the risk of stillbirth: a register- and population-based cohort of Danish pregnancies, 1997–2017

Abstract Background Nitrosatable drugs commonly prescribed during pregnancy can react with nitrite to form N-nitroso compounds which have been associated with an increased risk of stillbirth. Whether maternal residential drinking water nitrate modifies this association is unknown. We investigated, if household drinking water nitrate was associated with stillbirth, and if it modified the association between nitrosatable prescription drug intake and the risk of stillbirth. Methods We conducted an individual-level register- and population-based cohort study using 652,810 women with the first recorded singleton pregnancy in the Danish Medical Birth Registry between 1997 and 2017. Nitrosatable drug exposure was recorded by use of the Danish National Patient Registry defined as women with a first redeemed prescription of a nitrosatable drug the first 22 weeks of pregnancy. The reference group was women with no redeemed prescription of a nitrosatable drug in this period. The average individual drinking water nitrate concentration level (mg/L) was calculated in the same period. We categorized nitrosatable drugs as secondary amines, tertiary amines, and amides. Cox hazard regression was used to estimate crude and adjusted hazard ratios with 95% confidence intervals for stillbirth stratified into five categories of nitrate concentrations: ≤1 mg/L, > 1- ≤ 2 mg/L, > 2- ≤ 5 mg/L, > 5- ≤ 25 mg/L, and > 25 mg/L. Results Drinking water nitrate exposure in the population was not associated with the risk of stillbirth. Among 100,244 women who had a nitrosatable prescription drug redeemed ≤22 weeks of pregnancy of pregnancy, 418 (0.42%) had a stillbirth compared to 1993 stillbirths (0.36%) among 552,566 referent women. Women with any nitrosatable prescription drug intake and > 1- ≤ 2 mg/L nitrate concentration had an increased risk of stillbirth [adjusted hazard ratio 1.55 (95% confidence interval, 1.15–2.09)] compared with referent women. In the stratified analyses, the highest risk of stillbirth was found among women with secondary amine intake and > 25 mg/L nitrate concentrations [adjusted hazard ratio 3.11 (95% CI, 1.08–8.94)]. Conclusions The association between nitrosatable prescription drug intake and the risk of stillbirth may depend on the level of nitrate in household drinking water. Evaluations of the effect of nitrosatable drug intake on perinatal outcomes might consider nitrate exposure from drinking water.

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Increased Risk of Traffic Injury After a Cerebrovascular Event

Stroke ◽

10.1161/strokeaha.118.022657 ◽

2018 ◽

Vol 49 (12) ◽

pp. 3006-3011

Author(s):

Amy Y.X. Yu ◽

Moira K. Kapral ◽

Jiming Fang ◽

Donald A. Redelmeier

Keyword(s):

Transient Ischemic Attack ◽

Motor Vehicle ◽

Population Based ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Cerebrovascular Event ◽

Traffic Injury ◽

Increased Risk ◽

Ischemic Attack ◽

Serious Injuries

Background and Purpose— We aimed to determine the long-term risks of a motor vehicle collision after a cerebrovascular event and whether the risks were similar after left- or right-hemispheric events. Methods— We used a population-based registry to identify patients diagnosed with a transient ischemic attack or stroke (hemorrhagic or ischemic) between 2003 and 2013 in Ontario, Canada. Hemispheric laterality was determined using radiological and clinical findings. We identified subsequent serious injuries involving the patient as a driver using linked administrative data. Secondary outcomes included serious injuries involving the patient as a pedestrian, as a passenger, or other traumatic events (fall, fracture, ankle sprain). We used proportional hazard models accounting for death as a competing risk to test the association of hemispheric laterality and outcomes with and without adjustment for age, sex, discharge modified Rankin Scale score, home location, and prior driving record. Patients were followed through to 2017. Results— Among 26 144 patients with hemispheric cerebrovascular events, 377 subsequent serious traffic injuries as a driver (2.2 per 1000 person-year) were identified over a median follow-up of 6.4 person-years. The rate did not differ by laterality (adjusted hazard ratio, 1.00; 95% CI, 0.82–1.23). The risk of a serious traffic injury as a pedestrian was significantly higher after a right-sided than left-sided event (adjusted hazard ratio, 1.27; 95% CI, 1.02–1.58). Subsequent risks for other traumatic injuries did not differ by laterality of cerebrovascular event. Conclusions— The risk of a serious traffic injury as a pedestrian is substantially higher after a right-hemispheric cerebrovascular event compared with a left-sided event. Walking should be promoted for exercise in survivors of a stroke or transient ischemic attack, but these vulnerable road users may benefit from additional poststroke rehabilitation to optimize safety.

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Do Children With Constipation Have Increased Risk of Asthma? Real-World Data From a Nationwide Population-Based Cohort Study

Frontiers in Pediatrics ◽

10.3389/fped.2021.714406 ◽

2021 ◽

Vol 9 ◽

Author(s):

Yen-Chu Huang ◽

Meng-Che Wu ◽

Yu-Hsun Wang ◽

James Cheng-Chung Wei

Keyword(s):

Cohort Study ◽

Cox Regression ◽

Population Based ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Research Database ◽

Real World Data ◽

Childhood Disorders ◽

Cox Regression Analysis ◽

Increased Risk

Background: Asthma is one of the most burdensome childhood disorders. Growing evidence disclose intestinal dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microbiota. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess whether pediatric constipation influence the risk of developing asthma by a nationwide population-based cohort study.Methods: We analyzed 10,363 constipated patients and 10,363 individuals without constipation between 1999 and 2013 from Taiwan's National Health Insurance Research Database. Analysis of propensity score was utilized to match age, sex, comorbidities, and medications at a ratio of 1:1. In addition, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and a stratified analysis were performed.Results: After adjustment for age, sex, comorbidities, and medications, constipated patients had a 2.36-fold greater risk of asthma compared to those without constipation [adjusted hazard ratio (aHR): 2.36, 95% C.I. 2.04–2.73, p < 0.001]. Furthermore, the severity of constipation is associated with an increased risk of asthma; the adjusted hazard ratio was 2.25, 2.85, and 3.44 within < 3, 3–12, and ≥12 times of laxatives prescription within 1 year, respectively (p < 0.001).Conclusion: Constipation was correlated with a significantly increased risk of asthma. Pediatricians should be aware of the possibility of asthma in constipated patients. Further research is warranted to investigate the possible pathological mechanisms of this association.

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Maternal and child gluten intake and risk of type 1 diabetes: The Norwegian Mother and Child Cohort Study

10.1101/19001883 ◽

2019 ◽

Author(s):

Nicolai A Lund-Blix ◽

German Tapia ◽

Karl Mårild ◽

Anne Lise Brantsaeter ◽

Pål R Njølstad ◽

...

Keyword(s):

Type 1 Diabetes ◽

Cohort Study ◽

Confidence Interval ◽

Population Based ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Pregnancy Cohort ◽

Increased Risk ◽

Mother And Child

ABSTRACTOBJECTIVETo examine the association between maternal and child gluten intake and risk of type 1 diabetes in children.DESIGNPregnancy cohortSETTINGPopulation-based, nation-wide study in NorwayPARTICIPANTS86,306 children in The Norwegian Mother and Child Cohort Study born from 1999 through 2009, followed to April 15, 2018.MAIN OUTCOME MEASURESClinical type 1 diabetes, ascertained in a nation-wide childhood diabetes registry. Hazard ratios were estimated using Cox regression for the exposures maternal gluten intake up to week 22 of pregnancy and child’s gluten intake when the child was 18 months old.RESULTSDuring a mean follow-up of 12.3 years (range 0.7-16.0), 346 children (0.4%) developed type 1 diabetes (incidence rate 32.6 per 100,000 person-years). The average gluten intake was 13.6 grams/day for mothers during pregnancy, and 8.8 grams/day for the child at 18 months of age. Maternal gluten intake in mid-pregnancy was not associated with the development of type 1 diabetes in the child (adjusted hazard ratio 1.02 (95% confidence interval 0.73 to 1.43) per 10 grams/day increase in gluten intake). However, the child’s gluten intake at 18 months of age was associated with an increased risk of later developing type 1 diabetes (adjusted hazard ratio 1.46 (95% confidence interval 1.06 to 2.01) per 10 grams/day increase in gluten intake).CONCLUSIONSThis study suggests that the child’s gluten intake at 18 months of age, and not the maternal intake during pregnancy, could increase the risk of type 1 diabetes in the child.WHAT IS ALREADY KNOWN ON THIS TOPICA national prospective cohort study from Denmark found that a high maternal gluten intake during pregnancy could increase the risk of type 1 diabetes in the offspring (adjusted hazard ratio 1.31 (95% confidence interval 1.001 to 1.72) per 10 grams/day increase in gluten intake). No studies have investigated the relation between the amount of gluten intake by both the mother during pregnancy and the child in early life and risk of developing type 1 diabetes in childhood.WHAT THIS STUDY ADDSIn this prospective population-based pregnancy cohort with 86,306 children of whom 346 developed type 1 diabetes we found that the child’s gluten intake at 18 months of age was associated with the risk of type 1 diabetes (adjusted hazard ratio 1.46 (95% confidence interval 1.06 to 2.01) per 10 grams/day increase in gluten intake). This study suggests that the child’s gluten intake at 18 months of age, and not the maternal intake during pregnancy, could increase the child’s risk of type 1 diabetes.

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The Influence of Constipation on Asthma: A Real-world, Population-based Cohort Study

10.22541/au.161089372.23442799/v1 ◽

2021 ◽

Author(s):

Yen Chu Huang ◽

Meng Che Wu ◽

Yu-Hsun Wang ◽

James Cheng-Chung Wei

Keyword(s):

Cohort Study ◽

Cox Regression ◽

Population Based ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

World Population ◽

Research Database ◽

Cox Regression Analysis ◽

Increased Risk ◽

One Year

Background Among respiratory diseases, asthma is one of the most burdensome disorder worldwide. Growing evidence disclose gut dysbiosis may contribute to asthma via the gut-lung axis. Constipation can lead to alteration of the gut microflora. The clinical impact of constipation on asthma has not been researched. Therefore, we aim to assess the risk of asthma in constipated patients by a nationwide population-based cohort study. Methods We analyzed 82421 constipated patients and 82421 individuals without constipation between 1999 and 2013 from the Taiwanese National Health Insurance Research Database. Analysis of propensity score was utilized to match age, gender, comorbidities, and medications at a ratio of 1:1. Besides, multiple Cox regression analysis was performed to evaluate the adjusted hazard ratio of asthma. Furthermore, sensitivity tests and a stratified analysis were conducted. Results The incidence of asthma was 10.8 per 1,000 person-years in the constipation group, which was higher than the rate of 5.6 per 1,000 person-years observed in the non-constipation group. After adjustment for age, gender, comorbidities, and medications, constipated patients had a 1.91-fold greater risk of asthma compared to those without constipation (adjusted hazard ratio [aHR]: 1.91 (95% C.I. 1.84-1.99). In subgroup analyses, patients aged 20-39 years had a 2.04-fold highest risk of asthma in the constipation cohort (aHR:2.04, 95% CI, 1.84-2.26). Besides, the severity of constipation is associated with an increased risk of asthma; the aHR was 1.76 (1.69-1.85), 2.15(2.03-2.27), and 2.29(2.10-2.49) for < 3 times, 3-12 times, and ≥12 times of laxatives prescription within one year, respectively. (p<0.001) Moreover, constipated patients had a higher likelihood of asthma, regardless of gender, comorbidities, and medications. Conclusion Constipation relates to a significantly increased risk of asthma. Physicians should be aware of the possibility of asthma in constipated people. Further research is warranted to investigate the possible pathological mechanisms of this association.

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SARS-CoV-2 vaccination and myocarditis or myopericarditis: population based cohort study

BMJ ◽

10.1136/bmj-2021-068665 ◽

2021 ◽

pp. e068665

Author(s):

Anders Husby ◽

Jørgen Vinsløv Hansen ◽

Emil Fosbøl ◽

Emilia Myrup Thiesson ◽

Morten Madsen ◽

...

Keyword(s):

Cohort Study ◽

Confidence Interval ◽

Population Based ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Absolute Rate ◽

Hazard Ratios ◽

Increased Risk ◽

The Absolute

AbstractObjectiveTo investigate the association between SARS-CoV-2 vaccination and myocarditis or myopericarditis.DesignPopulation based cohort study.SettingDenmark.Participants4 931 775 individuals aged 12 years or older, followed from 1 October 2020 to 5 October 2021.Main outcome measuresThe primary outcome, myocarditis or myopericarditis, was defined as a combination of a hospital diagnosis of myocarditis or pericarditis, increased troponin levels, and a hospital stay lasting more than 24 hours. Follow-up time before vaccination was compared with follow-up time 0-28 days from the day of vaccination for both first and second doses, using Cox proportional hazards regression with age as an underlying timescale to estimate hazard ratios adjusted for sex, comorbidities, and other potential confounders.ResultsDuring follow-up, 269 participants developed myocarditis or myopericarditis, of whom 108 (40%) were 12-39 years old and 196 (73%) were male. Of 3 482 295 individuals vaccinated with BNT162b2 (Pfizer-BioNTech), 48 developed myocarditis or myopericarditis within 28 days from the vaccination date compared with unvaccinated individuals (adjusted hazard ratio 1.34 (95% confidence interval 0.90 to 2.00); absolute rate 1.4 per 100 000 vaccinated individuals within 28 days of vaccination (95% confidence interval 1.0 to 1.8)). Adjusted hazard ratios among female participants only and male participants only were 3.73 (1.82 to 7.65) and 0.82 (0.50 to 1.34), respectively, with corresponding absolute rates of 1.3 (0.8 to 1.9) and 1.5 (1.0 to 2.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively. The adjusted hazard ratio among 12-39 year olds was 1.48 (0.74 to 2.98) and the absolute rate was 1.6 (1.0 to 2.6) per 100 000 vaccinated individuals within 28 days of vaccination. Among 498 814 individuals vaccinated with mRNA-1273 (Moderna), 21 developed myocarditis or myopericarditis within 28 days from vaccination date (adjusted hazard ratio 3.92 (2.30 to 6.68); absolute rate 4.2 per 100 000 vaccinated individuals within 28 days of vaccination (2.6 to 6.4)). Adjusted hazard ratios among women only and men only were 6.33 (2.11 to 18.96) and 3.22 (1.75 to 5.93), respectively, with corresponding absolute rates of 2.0 (0.7 to 4.8) and 6.3 (3.6 to 10.2) per 100 000 vaccinated individuals within 28 days of vaccination, respectively. The adjusted hazard ratio among 12-39 year olds was 5.24 (2.47 to 11.12) and the absolute rate was 5.7 (3.3 to 9.3) per 100 000 vaccinated individuals within 28 days of vaccination.ConclusionsVaccination with mRNA-1273 was associated with a significantly increased risk of myocarditis or myopericarditis in the Danish population, primarily driven by an increased risk among individuals aged 12-39 years, while BNT162b2 vaccination was only associated with a significantly increased risk among women. However, the absolute rate of myocarditis or myopericarditis after SARS-CoV-2 mRNA vaccination was low, even in younger age groups. The benefits of SARS-CoV-2 mRNA vaccination should be taken into account when interpreting these findings. Larger multinational studies are needed to further investigate the risks of myocarditis or myopericarditis after vaccination within smaller subgroups.

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The Risks for Ovarian, Endometrial, Breast, Colorectal, and Other Cancers in Women With Newly Diagnosed Endometriosis or Adenomyosis: A Population-Based Study

International Journal of Gynecological Cancer ◽

10.1097/igc.0000000000000454 ◽

2015 ◽

Vol 25 (6) ◽

pp. 968-976 ◽

Cited By ~ 58

Author(s):

Victor C. Kok ◽

Horng-Jyh Tsai ◽

Chi-Feng Su ◽

Chien-Kuan Lee

Keyword(s):

Health Insurance ◽

Population Based ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Research Database ◽

Newly Diagnosed ◽

Ovarian Endometriosis ◽

Increased Risk ◽

Comparison Cohort

ObjectiveRecent studies report a link between endometriosis and ovarian cancer (OC). Using a population-based cohort study to confirm the association between endometriosis and cancer is desirable. We thus examined the magnitude of the risks of OC, endometrial cancer (EC), breast cancer, colorectal cancer (CRC), and other cancers in women with newly diagnosed endometriosis or adenomyosis (internal endometriosis).Methods/MaterialsWomen older than 20 years with claims data between 2003 and 2005 were identified from the Longitudinal Health Insurance Dataset containing 1 million individuals randomly sampled from the National Health Insurance Research Database. Those with preexisting malignancies, hysterectomy, or oophorectomy were excluded. The endometriosis cohort (n = 2266, including 768 cases of pure adenomyosis) and comparison cohort (n = 9064), formed by 1:4 matching, were followed up until incidence cancer, dropout, or December 31, 2008. Outcome measures included cancer incidence and adjusted hazard ratio by Cox model adjusted for age group, comorbidities, and endometriosis medication use.ResultsWith 9842 person-years of follow-up in endometriosis cohort and 36,274 person-years of follow-up in comparison cohort, there were increased risks of all cancers (adjusted hazard ratio, 1.8; 95% confidence interval, 1.4–2.4), OC (4.56, 1.72–12.11), and EC (4.05, 1.20–13.66). The ovarian endometriosis group was associated with increased risk of subsequent OC (4.37, 1.07–17.83). The adenomyosis group was strongly associated with both OC (5.50, 1.95–15.50) and EC (5.13, 1.36–19.40). Increased risk of subsequent CRC was observed in women with adenomyosis with coexistent endometriosis at other sites (13.04, 2.21–77.04). However, no statistically significant increased risk of breast or other cancers was observed.ConclusionsHaving limitations such as lacking of parity information which may affect the magnitude of risk estimates, this study demonstrates that ovarian endometriosis has a 4-fold increased risk of OC. Adenomyosis may associate with a 4- to 5-fold increased risk of OC and EC, and unexpectedly, a 13-fold increased risk of CRC.

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Increased risk of valvular heart disease in patients with ankylosing spondylitis: a nationwide population-based longitudinal cohort study

Therapeutic Advances in Musculoskeletal Disease ◽

10.1177/1759720x211021676 ◽

2021 ◽

Vol 13 ◽

pp. 1759720X2110216

Author(s):

Wun-Zhih Siao ◽

Chin-Hsiu Liu ◽

Yu-Hsun Wang ◽

James Cheng-Chung Wei ◽

Gwo-Ping Jong

Keyword(s):

Cohort Study ◽

Heart Disease ◽

Health Insurance ◽

Ankylosing Spondylitis ◽

Subgroup Analysis ◽

Valvular Heart Disease ◽

Population Based ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Increased Risk

Aims: We aimed to evaluate the risk of valvular heart disease (VHD) among patients with ankylosing spondylitis (AS). Methods: This was a population-based cohort study utilizing the Longitudinal Health Insurance Research Database of the National Health Insurance in Taiwan. Patients with and without coding of newly diagnosed AS from 1999 to 2013 were assigned to the AS and non-AS groups, respectively. Primary outcome was the incidental risk of VHD. Multiple Cox regression was used to estimate the adjusted hazard ratio of VHD. Subgroup analysis and sensitivity tests were also conducted. Results: The AS group included 3780 patients, and 22,680 matched subjects without an AS diagnosis were identified as controls. The AS group had an increased risk of VHD compared with non-AS controls (adjusted hazard ratio: 1.63; 95% confidence interval: 1.43–1.86; p < 0.001). Subgroup analysis also revealed an increased risk of individual types of VHD, including aortic, mitral, and tricuspid valve disease. Patients in the AS group had a higher incidence of valve replacement surgery after the onset of VHD. Conclusion: Patients with AS had a significant risk of VHD compared to non-AS controls in this population-based cohort study. Screening for VHD may be needed in caring patients with AS. We suggest that echocardiography may be performed when patients are diagnosed with AS.

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Association Between the APOE ɛ2/ɛ4 Genotype and Alzheimer’s Disease and Mild Cognitive Impairment Among African Americans

Journal of Alzheimer s Disease ◽

10.3233/jad-201613 ◽

2021 ◽

pp. 1-6

Author(s):

Dianxu Ren ◽

Oscar L. Lopez ◽

Jennifer H. Lingler ◽

Yvette Conley

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

African Americans ◽

Hazard Ratio ◽

Adjusted Hazard Ratio ◽

Increased Risk ◽

Similar Risk

We examined the association between APOE ɛ2/ɛ4 with incident Alzheimer’s disease (AD) and mild cognitive impairment (MCI) among African Americans using the national dataset from the National Alzheimer’s Coordinating Center (NACC) from 2005 to September 2019. Compared to ɛ3/ɛ3 carriers, ɛ2/ɛ4 carriers exhibited a similar risk of incident AD (adjusted hazard ratio [aHR] = 0.85, 95% CI [0.39, 1.84]) among the AD cohort and similar risk of incident MCI (aHR = 0.88, 95% CI [0.51, 1.50]) among the MCI cohort. Our findings suggest that, unlike the increased risk of AD and MCI in non-Latino whites, APOE ɛ2/ɛ4 genotype is not associated with the incidence of AD and MCI among African Americans.

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Systemic sclerosis portends increased risk of conduction and rhythm abnormalities at diagnosis and during disease course: A US population-based cohort

Journal of Scleroderma and Related Disorders ◽

10.1177/23971983211034074 ◽

2021 ◽

pp. 239719832110340

Author(s):

Yasser A Radwan ◽

Reto D Kurmann ◽

Avneek S Sandhu ◽

Edward A El-Am ◽

Cynthia S Crowson ◽

...

Keyword(s):

Risk Factors ◽

Pulmonary Hypertension ◽

Systemic Sclerosis ◽

Confidence Interval ◽

Cumulative Incidence ◽

Disease Onset ◽

Population Based ◽

Hazard Ratio ◽

Conduction Disorders ◽

Increased Risk

Objectives: To study the incidence, risk factors, and outcomes of conduction and rhythm disorders in a population-based cohort of patients with systemic sclerosis versus nonsystemic sclerosis comparators. Methods: An incident cohort of patients with systemic sclerosis (1980–2016) from Olmsted County, MN, was compared to age- and sex-matched nonsystemic sclerosis subjects (1:2). Electrocardiograms, Holter electrocardiograms, and a need for cardiac interventions were reviewed to determine the occurrence of any conduction or rhythm abnormalities. Results: Seventy-eight incident systemic sclerosis cases and 156 comparators were identified (mean age 56 years, 91% female). The prevalence of any conduction disorder before systemic sclerosis diagnosis compared to nonsystemic sclerosis subjects was 15% versus 7% ( p = 0.06), and any rhythm disorder was 18% versus 13% ( p = 0.33). During a median follow-up of 10.5 years in patients with systemic sclerosis and 13.0 years in nonsystemic sclerosis comparators, conduction disorders developed in 25 patients with systemic sclerosis with cumulative incidence of 20.5% (95% confidence interval: 12.4%–34.1%) versus 28 nonsystemic sclerosis patients with cumulative incidence of 10.4% (95% confidence interval: 6.2%–17.4%) (hazard ratio: 2.57; 95% confidence interval: 1.48–4.45), while rhythm disorders developed in 27 patients with systemic sclerosis with cumulative incidence of 27.3% (95% confidence interval: 17.9%–41.6%) versus 43 nonsystemic sclerosis patients with cumulative incidence of 18.0% (95% confidence interval: 12.3%–26.4%) (hazard ratio: 1.62; 95% confidence interval: 1.00–2.64). Age, pulmonary hypertension, and smoking were identified as risk factors. Conclusion: Patients with systemic sclerosis have an increased risk of conduction and rhythm disorders both at disease onset and over time, compared to nonsystemic sclerosis patients. These findings warrant increased vigilance and screening for electrocardiogram abnormalities in systemic sclerosis patients with pulmonary hypertension.

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Long-Term Survival Among Patients With Hodgkin's Lymphoma Who Developed Breast Cancer: A Population-Based Study

Journal of Clinical Oncology ◽

10.1200/jco.2010.29.5683 ◽

2010 ◽

Vol 28 (34) ◽

pp. 5088-5096 ◽

Cited By ~ 52

Author(s):

Michael T. Milano ◽

Huilin Li ◽

Mitchell H. Gail ◽

Louis S. Constine ◽

Lois B. Travis

Keyword(s):

Breast Cancer ◽

Cardiac Disease ◽

Hodgkin’S Lymphoma ◽

Large Population ◽

Population Based ◽

Hazard Ratio ◽

Hodgkin's Lymphoma ◽

Term Survival ◽

Distant Disease ◽

Increased Risk

Purpose The increased risk of breast cancer (BC) among women receiving chest radiotherapy for Hodgkin's lymphoma (HL) is well-established. However, there are no large population-based studies that describe overall survival (OS) and cause-specific survival (CSS) compared with women with first primary BC. Methods For 298 HL survivors who developed BC (HL-BC group) and 405,223 women with a first or only BC (BC-1 group), actuarial OS and CSS were compared, accounting for age, BC stage, hormone receptor status, sociodemographic status, radiation for HL, and other variables. All patients were derived from the population-based Surveillance, Epidemiology, and End Results program. Results OS among patients with HL-BC was significantly inferior that of to patients with BC-1: 15-year OS was 48% versus 69% (P < .0001) for localized BC, and 33% versus 43% (P < .0001) for regional/distant BC. Patients with HL-BC had a significantly increased seven-fold risk (P < .0001) of death from other cancers (ie, not HL or BC) compared with patients with BC-1. Mortality from heart disease among patients with HL-BC with either localized or regional/distant disease was also significantly increased (hazard ratio = 2.22, P = .04; and hazard ratio = 4.28, P = .02, respectively) compared with patients with BC-1. Although 10-year BC-CSS was similar for patients with HL-BC and BC-1 with regional/distant disease, it was inferior for patients with localized BC (82% v 88%, respectively; P = .002). Conclusion Women with HL may survive a subsequent diagnosis of BC, only to experience significant excesses of death from other primary cancers and cardiac disease. Greater awareness of screening for cardiac disease and subsequent primary cancers in patients with HL-BC is warranted.

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