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Biomedical subjects

Morten Frisch

Publications and source records attributed to Morten Frisch.

At least 19 recordsLinked to original sources

Reproductive patterns and non-Hodgkin lymphoma risk in Danish women and men.

Reproductive patterns have been inconsistently linked to risk of non-Hodgkin lymphoma (NHL) in women, and fathering patterns in relation to NHL risk have not been studied. The authors conducted a register-based cohort study of 4.1 million Danes to investigate associations of livebirths with subsequent NHL incidence (85 million person-years, 3819 NHL cases). The impact of induced abortions, ectopic pregnancies, spontaneous abortions, missed abortions, stillbirths, and hydatidiform moles on subsequent NHL incidence was studied in a subcohort of 1.2 million women. Ratios of NHL incidence rates, accompanying trend tests and two-sided p-values were calculated by log-linear Poisson regression analyses. Pregnancies, whether ending in livebirths or not, were unrelated to NHL incidence in women. The only statistically significant finding in women was that, among parous women, age at first child-birth was inversely associated with NHL incidence (p-trend = 0.001). In men, there was no overall difference in NHL incidence between fathers and non-fathers. However, in men with children, NHL risk declined with increasing number of children (p-trend = 0.02) and increased with time since birth of the most recent child (p-trend < 0.001). Pregnancies have limited impact, if any, on subsequent NHL risk in women. Our findings in men need replication, but, if verified, they may reflect lymphomagenesis-associated male subfertility prior to NHL diagnosis.

Cohort Studies↗

Sibship characteristics and risk of multiple sclerosis: a nationwide cohort study in Denmark.

It has been hypothesized that age at infection with a common microbial agent may be associated with the risk of multiple sclerosis (MS). The authors addressed this hypothesis by using number of older siblings and other sibship characteristics as an approximation of age at exposure to common infections. Data on family characteristics and vital status from the Danish Civil Registration System were used to establish a cohort of all Danes whose mothers had been born in Denmark since 1935. Persons diagnosed with MS during the period 1968-1998 were identified through linkage with the Danish Multiple Sclerosis Register. The cohort of 1.9 million Danes was followed for 28.1 million person-years; during that time, 1,036 persons developed MS. Overall, there was no association between number of older siblings, number of younger siblings, total number of siblings, age distance from the nearest younger sibling, or exposure to younger siblings under 2 years of age and risk of MS later in life. There was no association of MS risk with multiple birth (vs. singleton birth) or with the age of the mother or father at birth. These results do not lend support to the hypothesis that number of older siblings or any of the other sibship characteristics studied is associated with risk of MS.

Adolescent↗

Socioeconomic status and risk of rheumatoid arthritis: a Danish case-control study.

OBJECTIVE: To examine whether markers of socioeconomic status (SES) are associated with risk of rheumatoid arthritis (RA), and if so, whether selected lifestyle-related factors could explain this association. METHODS: We conducted a frequency matched case-control study; subjects comprised 515 patients (participation rate 83%) attending rheumatology and internal medicine departments in Denmark, with recently diagnosed RA according to the American College of Rheumatology (ACR) 1987 classification criteria for RA (mean disease duration 2.3 yrs), and 769 frequency-matched population controls (participation rate 64%). Information about SES and environmental exposure was obtained by structured telephone interview. Logistic regression analyses evaluated the role of markers of SES. RESULTS: Level of education was significantly inversely associated with risk of RA, with a 2-fold lower risk of RA among those with the longest formal education compared with those having the lowest level of education (multivariate odds ratio = 0.43, 95% confidence interval 0.24-0.76, p trend = 0.001). None of a series of studied lifestyle factors could explain this finding in multivariate logistic regression analyses. When dividing the RA cases into clinical subgroups, the inverse association with level of education was found to apply predominantly to rheumatoid factor (RF)-positive RA. CONCLUSION: The inverse association between level of education and risk of RF-positive RA was not explained by any of the examined lifestyle factors. RF-positive and RF-negative RA may be 2 distinct diseases with different etiologies, with unmeasured factors related to educational level predominantly associated with the risk of RF-positive RA. However, because mechanisms underlying referral to a hospital might be linked to educational level, our observation based on hospital-referred RA patients should be evaluated cautiously. The study stresses the importance of taking SES measures into account in studies that aim at identifying environmental risk factors for RA.

Adolescent↗

Type 1 diabetes and multiple sclerosis: A Danish population-based cohort study.

BACKGROUND: Type 1 diabetes mellitus (T1D) and multiple sclerosis (MS) contribute considerably to the burden of autoimmune diseases in young adults. Although HLA patterns of T1D and MS are considered mutually exclusive, individual and familial co-occurrence of the 2 diseases has been reported. OBJECTIVE: To assess the co-occurrence of T1D and MS by estimating the risk for MS in patients with T1D and the risk for T1D in first-degree relatives of patients with MS. DESIGN, SETTING, AND PARTICIPANTS: Two population-based disease registers, the Danish Hospital Discharge Register and the Danish Multiple Sclerosis Register were used to identify patients with T1D, defined as patients in whom diabetes was diagnosed before age 20 years (N = 6078), and patients with MS (N = 11 862). First-degree relatives (N = 14,771) of patients with MS were identified from family information in the Danish Civil Registration System. MAIN OUTCOME MEASURE: Patients with T1D and first-degree relatives of patients with MS were followed up for occurrence of MS and T1D, respectively, and the relative risks were expressed as standardized incidence ratios, that is, ratios of observed to expected numbers of outcomes based on national age, sex, and period-specific MS and T1D incidence rates. RESULTS: Patients with T1D were at more than 3-fold increased risk for development of MS (relative risk, 3.26; 95% confidence interval, 1.80-5.88; n = 11). First-degree relatives of patients with MS were at 63% increased risk (relative risk, 1.63; 95% confidence interval, 1.26-2.12; n = 56) for development of T1D. However, adjusting for familial relationship to patients with T1D reduced the excess risk to 44% (relative risk, 1.44; 95% confidence interval, 1.11-1.88; n = 56). CONCLUSION: The present nationwide cohort study demonstrates an intraindividual and, to a lesser degree, an intrafamilial co-occurrence of MS and T1D.

Adolescent↗

Childhood family correlates of heterosexual and homosexual marriages: a national cohort study of two million Danes.

Children who experience parental divorce are less likely to marry heterosexually than those growing up in intact families; however, little is known about other childhood factors affecting marital choices. We studied childhood correlates of first marriages (heterosexual since 1970, homosexual since 1989) in a national cohort of 2 million 18-49 year-old Danes. In multivariate analyses, persons born in the capital area were significantly less likely to marry heterosexually, but more likely to marry homosexually, than their rural-born peers. Heterosexual marriage was significantly linked to having young parents, small age differences between parents, stable parental relationships, large sibships, and late birth order. For men, homosexual marriage was associated with having older mothers, divorced parents, absent fathers, and being the youngest child. For women, maternal death during adolescence and being the only or youngest child or the only girl in the family increased the likelihood of homosexual marriage. Our study provides population-based, prospective evidence that childhood family experiences are important determinants of heterosexual and homosexual marriage decisions in adulthood.

Child↗

Environmental risk factors differ between rheumatoid arthritis with and without auto-antibodies against cyclic citrullinated peptides.

The aim of this study was to evaluate new and previously hypothesised non-genetic risk factors for serologic subtypes of rheumatoid arthritis (RA) defined by the presence or absence of auto-antibodies to cyclic citrullinated peptides (CCP). In a national case-control study, we included 515 patients recently diagnosed with RA according to the American College of Rheumatology 1987 classification criteria and 769 gender- and age-matched population controls. Telephone interviews provided information about non-genetic exposures, and serum samples for patients were tested for anti-CCP-antibodies. Associations between exposure variables and risk of anti-CCP-positive and anti-CCP-negative RA were evaluated using logistic regression. A series of RA subtype-specific risk factors were identified. Tobacco smoking (odds ratio [OR] = 1.65; 95% confidence interval: 1.03-2.64, for > 20 versus 0 pack-years) was selectively associated with risk of anti-CCP-positive RA, whereas alcohol consumption exhibited an inverse dose-response association with this RA subtype (OR = 1.98, 1.22-3.19, for 0 versus > 0-5 drinks per week). Furthermore, coffee consumption (OR = 2.18; 1.07-4.42, for > 10 versus 0 cups per day), ever use of oral contraceptives (OR = 1.65; 1.06-2.57) and having a first-degree relative with schizophrenia (OR = 4.18; 1.54-11.3) appeared more strongly associated with risk of anti-CCP-positive RA. Obesity was selectively associated with risk of anti-CCP-negative RA, with obese individuals being at more than 3-fold increased risk of this subtype compared with normal-weight individuals (OR = 3.45; 1.73-6.87). Age at menarche was the only examined factor that was significantly associated with both serologic subtypes of RA (p-trends = 0.01); women with menarche at age > or = 15 years had about twice the risk of either RA subtype compared with women with menarche at age < or = 12 years. Major differences in risk factor profiles suggest distinct etiologies for anti-CCP-positive and anti-CCP-negative RA.

Adolescent↗

Familial risk of multiple sclerosis: a nationwide cohort study.

Multiple sclerosis (MS) is known to accumulate within families. The magnitude of the familial risk, however, remains uncertain. Using a nationwide MS register and other national registers, the authors estimated relative and absolute risks of MS in a population-based cohort that included 19,615 first-degree relatives of 8,205 Danish MS patients followed from 1968 to 1997. The ratio of observed to expected numbers of MS cases served as the measure of the relative risk of MS. Lifetime risks of MS in first-degree relatives were estimated as the product of the relative risk and the national lifetime risk of MS. Overall, first-degree relatives had a sevenfold increased risk of MS (relative risk=7.1, 95% confidence interval: 5.8, 8.8) (n=90) compared with the background population. By modeling the individual incidence rate of MS as the sum of a familial component and a sporadic risk component, the familial excess lifetime risk was found to be 2.5% (95% confidence interval: 2.0, 3.2) among first-degree relatives of MS patients, irrespective of the gender of the proband and the relative. This percentage should be added to a sporadic absolute risk in the general population of 0.5% in women and 0.3% for men. Spouses of MS patients did not experience an increased risk of MS, suggesting no major role for environmental factors acting in adulthood.

Denmark↗

Diet and risk of rheumatoid arthritis in a prospective cohort.

OBJECTIVE: To assess the association between dietary factors and risk of rheumatoid arthritis (RA) in a large prospective cohort. METHODS: Information about dietary intake was obtained from a detailed self-administered food frequency questionnaire completed by 57,053 individuals who participated in a prospective cohort. Linking the cohort to the Danish National Patient Registry we identified patients who developed RA. A rheumatologist scrutinized original medical records for these individuals in order to confirm the diagnosis of RA. Cox proportional hazards regression analyses were performed for dietary and lifestyle factors. RESULTS: The average time of followup in the cohort was 5.3 years (range < 1 mo to 7.7 yrs). Sixty-nine individuals were identified with confirmed incident RA. In multivariate models each increase in intake of 30 g fat fish (> or = 8 g fat/100 g fish) per day was associated with 49% reduction in the risk of RA (p = 0.06), whereas medium fat fish (3-7 g fat/100 g fish) was associated with significantly increased risk of RA. Intake of fruit and coffee was not associated with risk of RA. Furthermore, no associations were found between risk of RA and intake of a range of other dietary factors including long chain fatty acids, olive oil, vitamins A, E, C, D, zinc, selenium, iron, and meat. CONCLUSION: The limited number of patients who developed RA during followup of our large cohort prevented us from concluding that dietary factors are unimportant as risk factors for RA. It appears, however, that if dietary factors are important modifiers of RA risk, they must play a role more than a few years before clinical diagnosis.

Adult↗

Childhood infections and risk of multiple sclerosis.

Multiple sclerosis has been hypothesized to be the result from an aberrant immune response possibly triggered by delayed exposure to a common childhood infection. Because the vast majority of previous studies testing this hypothesis have been based on a history of childhood infections recalled years to decades later in adulthood, we investigated whether age at six common childhood infections was associated with risk of multiple sclerosis, using information recalled in the childhood of a historical cohort of school children in Denmark. Cases included all individuals with multiple sclerosis in the country born between 1940 and 1975, who had attended school in the capital, Copenhagen. Controls were age- and sex-matched peers. School health records were obtained for all subjects. The records contained information on measles, pertussis, scarlet fever, birth order, sibship size, social class of the father, school years, and name of school and attended school classes for children born since 1940 (n(cases) = 455, n(controls) = 1801). For children born since 1950, the records also contained information on rubella, varicella and mumps (n(cases) = 182, n(controls) = 690). Neither age at infection with measles, rubella, varicella, mumps, pertussis and scarlet fever (upper age limit, 14 years) nor the cumulative number of these infections between the ages of 10 and 14 years was associated with the risk of multiple sclerosis. In addition, the risk of multiple sclerosis was not associated with birth order or social class. No clustering of multiple sclerosis in school classes was observed. Our findings suggest that measles, rubella, mumps, varicella, pertussis and scarlet fever, even if acquired late in childhood, are not associated with increased risk of multiple sclerosis later in life.

Adolescent↗

Validity of rheumatoid arthritis diagnoses in the Danish National Patient Registry.

Discharge diagnoses following hospital admissions in Denmark are recorded in the Danish National Patient Registry (NPR). Such routine hospitalization records may serve as useful research tools in epidemiological studies. The aim of the study was to provide measures of the validity and completeness of rheumatoid arthritis (RA) diagnoses recorded in the NPR. We identified medical records for 217 patients recorded as having RA in the NPR between 1977 and 2001. Using two definitions of RA (clinically confirmed RA and fulfilment of the American College of Rheumatology (ACR) 1987 diagnostic criteria for RA), a rheumatologist assessed the proportion of RA diagnoses recorded in the NPR that could be confirmed by scrutiny of the original medical records. The completeness of RA diagnoses in the NPR was estimated by a two-sample capture-recapture method. Overall, 59% of the 217 RA diagnoses in the NPR were confirmed by information in the medical records. However, major differences were seen according to characteristics of the underlying hospital registrations. Generally, RA diagnoses were most often confirmed for patients registered as inpatients and for patients with more than one hospital registration with RA. Specifically, only 42% of patients with one RA registration from a rheumatology department were confirmed as having RA. In contrast, 91% of patients treated at a rheumatology department and having three or more hospital registrations with RA were confirmed as having RA. The completeness of the NPR with respect to RA satisfying the ACR 1987 classification criteria was estimated to 26%. Our conclusion is that with careful attention to the limitations in the data, discharge diagnoses for patients with records of RA in the Danish NPR can be used for epidemiological research purposes; however, our findings prompt general carefulness when using non-audited registries for research in RA.

Adolescent↗

Characteristics of Hodgkin's lymphoma after infectious mononucleosis.

BACKGROUND: Infectious mononucleosis-related Epstein-Barr virus (EBV) infection has been associated with an increased risk of Hodgkin's lymphoma in young adults. Whether the association is causal remains unclear. METHODS: We compared the incidence rates of Hodgkin's lymphoma in two population-based Danish cohorts of patients who were tested for infectious mononucleosis: 17,045 with serologic evidence of having had acute EBV infection, and 24,614 with no such evidence. We combined the cohort of patients who had serologically verified infectious mononucleosis with a cohort of 21,510 Swedish patients with infectious mononucleosis (combined total, 38,555). Biopsy specimens of Hodgkin's lymphomas occurring during follow-up in this combined cohort were tested serologically for the presence of EBV. Using this information, we modeled the relative risk of EBV-negative and EBV-positive Hodgkin's lymphoma in different periods after the diagnosis of infectious mononucleosis and estimated the median incubation time for mononucleosis-related EBV-positive Hodgkin's lymphoma. RESULTS: Only serologically confirmed infectious mononucleosis was associated with a persistently increased risk of Hodgkin's lymphoma. Sixteen of 29 tumors (55 percent), obtained from patients with infectious mononucleosis, had evidence of EBV. There was no evidence of an increased risk of EBV-negative Hodgkin's lymphoma after infectious mononucleosis. In contrast, the risk of EBV-positive Hodgkin's lymphoma was significantly increased (relative risk, 4.0; 95 percent confidence interval, 3.4 to 4.5). The estimated median incubation time from mononucleosis to EBV-positive Hodgkin's lymphoma was 4.1 years (95 percent confidence interval, 1.8 to 8.3). CONCLUSIONS: A causal association between infectious mononucleosis-related EBV infection and the EBV-positive subgroup of Hodgkin's lymphomas is likely in young adults.

Adolescent↗

Childhood exposure to simian virus 40-contaminated poliovirus vaccine and risk of AIDS-associated non-Hodgkin's lymphoma.

Persons with acquired immunodeficiency syndrome (AIDS) have increased risk for non-Hodgkin's lymphoma (NHL). Recent studies have reported the detection of DNA sequences from simian virus 40 (SV40), a macaque polyomavirus that contaminated early poliovirus vaccines, in a large proportion of AIDS-associated NHLs. To examine the association between SV40 exposure and NHL risk, we analyzed data from a U.S. registry-based cohort study of persons with AIDS (1980-96). We calculated NHL incidence in persons born in 1958-61 (exposed to SV40-contaminated poliovirus vaccine as children, n = 39,468) and in 1964-67 (born after vaccines were cleared of SV40 and thus unexposed, n = 17,340). Among persons with AIDS, NHL incidence was 11.7 per 1,000 person-years in SV40-exposed individuals (616 NHL cases) and 10.1 per 1,000 person-years in SV40-unexposed individuals (230 cases; unadjusted relative risk 1.15, 95% CI 0.99-1.34, p = 0.06). Because of differences in cohorts' birth years and the evolving demographics of the AIDS epidemic, SV40-exposed subjects were older at AIDS onset than unexposed subjects (mean age 32.0 vs. 27.2 years, p < 0.0001), and the cohorts differed by sex (p < 0.0001) and ethnic group (p < 0.0001). Since NHL incidence was relatively high among whites (p < 0.0001) and homosexual males (p < 0.0001) and increased with age (p = 0.09), comparisons required adjustments for these factors. After adjustment, SV40 exposure was not associated with NHL incidence (adjusted relative risk 0.97, 95% CI 0.79-1.20, p = 0.80). We conclude that childhood exposure to SV40 through receipt of contaminated poliovirus vaccine was not associated with increased risk for AIDS-associated NHL. Our findings do not support a role for SV40 in lymphomagenesis among immunosuppressed persons.

Adolescent↗

Cancer in a population-based cohort of men and women in registered homosexual partnerships.

Cancer patterns among broad populations of homosexual men and women have not been studied systematically. The authors followed 1,614 women and 3,391 men in Denmark for cancer from their first registration for marriage-like homosexual partnership between 1989 and 1997. Ratios of observed to expected cancers measured relative risk. Women in homosexual partnerships had cancer risks similar to those of Danish women in general (overall relative risk (RR) = 0.9, 95% confidence interval (CI): 0.6, 1.4), but only one woman developed cervical carcinoma in situ versus 5.8 women expected (RR = 0.2, 95% CI: 0.0, 0.97). Overall, men in homosexual partnerships were at elevated cancer risk (RR = 2.1, 95% CI: 1.8, 2.5), due mainly to human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS)-associated Kaposi's sarcoma (RR = 136, 95% CI: 96, 186) and non-Hodgkin's lymphoma (RR = 15.1, 95% CI: 10.4, 21.4). Anal squamous carcinoma also occurred in excess (RR = 31.2, 95% CI: 8.4, 79.8). After exclusion of Kaposi's sarcoma, non-Hodgkin's lymphoma, and anal squamous carcinoma, no unusual cancer risk remained (RR = 1.0, 95% CI: 0.8, 1.3). With anal squamous carcinoma and HIV/AIDS-associated cancers as notable exceptions in men, cancer incidence rates among homosexual persons in marriage-like partnerships are similar to those prevailing in society at large.

Acquired Immunodeficiency Syndrome↗

Cancer incidence in Denmark following exposure to poliovirus vaccine contaminated with simian virus 40.

BACKGROUND: Early poliovirus vaccines were accidentally contaminated with simian virus 40 (SV40). In Denmark, poliovirus vaccine was administered to most children from 1955 through 1961. SV40 DNA sequences have been detected in several human malignancies, including mesothelioma, ependymoma, choroid plexus tumors, and non-Hodgkin's lymphoma. To clarify whether SV40 infection increases risk of these cancers or of cancers arising in children, we examined cancer incidence in three Danish birth cohorts. METHODS: Population-based cancer incidence data from 1943 through 1997 were obtained from the Danish Cancer Registry. The relationship between exposure to SV40-contaminated vaccine and cancer incidence was evaluated by examining incidence in birth cohorts that differed in exposure to SV40-contaminated vaccine. In addition, cancer incidence was examined in children who were 0-4 years of age before, during, and after the period of vaccine contamination. Incidence was compared using Poisson regression, adjusting for age differences. All statistical tests were two-sided. RESULTS: After 69.5 million person-years of follow-up, individuals exposed to SV40-contaminated poliovirus vaccine as infants (i.e., born 1955-1961) or children (i.e., born 1946-1952) had lower overall cancer risk (age-adjusted relative risk [RR] = 0.86, 95% confidence interval [CI] = 0.81 to 0.91 and RR = 0.79, 95% CI = 0.75 to 0.84, respectively; P<.001 for both) than unexposed individuals (i.e., born 1964-1970, after the vaccine was cleared of SV40 contamination). Specifically, SV40 exposure was not associated with increased incidence of mesothelioma, ependymoma, choroid plexus tumor, or non-Hodgkin's lymphoma. After 19.5 million person-years of follow-up, incidence of all cancers combined, of intracranial tumors, and of leukemia among children aged 0-4 years was also not associated with SV40 exposure. Ependymoma incidence was higher during the exposed period than during the unexposed period (RR = 2.59, 95%CI = 1.36 to 4.92; P =.004 versus the period before contamination); however, incidence peaked in 1969, after the vaccine was cleared of SV40. CONCLUSION: Exposure to SV40-contaminated poliovirus vaccine in Denmark was not associated with increased cancer incidence.

Child, Preschool↗