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Biomedical subjects

M Melbye

Publications and source records attributed to M Melbye.

At least 91 records · Page 5Linked to original sources
PubMed1997

Risk of second cancers in classical Kaposi's sarcoma.

An association between Kaposi's sarcoma (KS) and malignant lymphoma has been suspected for many years. Both cancers belong to the group of malignancies associated with immune suppression and have been known to occur in the same individual. Accordingly, a common etiology has been suspected. Through linkage within the Nordic cancer registries, we studied the occurrence of cancers in a population-based cohort of 741 patients with classical KS. The relative risk of subsequent malignancies was expressed as the ratio of the observed numbers of cancer to the numbers expected based on age-, sex-, period- and country-specific incidence rates, i.e., the standardized incidence ratio (SIR). A total of 104 cancers was observed during 5,802 person-years of follow-up, which was close to the expected 98.8 cases (SIR, 1.05). During the first year of follow-up, 3 lymphomas were observed, which is in significant excess of the 0.2 lymphomas expected (SIR, 13.0). In contrast, no lymphomas occurred in the period beyond the first year of follow-up vs. 2.3 expected. Cancers of the buccal cavity and pharynx (SIR, 10.6; n = 4) and of the colon (SIR, 2.7; n = 7) occurred in excess among women but not among men. Accordingly, our results indicate that patients with classical KS are not at increased risk of cancer in general. In particular, the overall risk of lymphomas was not significantly increased. The high relative risk of malignant lymphoma immediately after KS was based on a limited number of cases, and this observation is unlikely to indicate a common etiology.

Age Factors↗
PubMed1997

HPV detection in children prior to sexual debut.

Knowledge of the epidemiology of infection with human papillomavirus (HPV) in childhood is important, since HPV infection early in life could represent a risk factor for later development of anogenital cancer. A random sample of Danish children aged 0 to 17 years was tested for the presence of HPV in the anal region and the oral cavity by the polymerase chain reaction using a consensus HPV L1 primer. Only 4 of 249 anal beta-globin-positive samples and one of 392 oral beta-globin-positive samples were HPV-positive. All HPV-positive samples were of unknown types. We conclude that the prevalence of anogenital HPV infection in childhood is very low indeed and that the oral cavity does not seem to act as a reservoir for HPV infection in childhood. This indicates that anogenital types of HPV are not transmitted to any measureable degree by non-sexual routes and further supports the notion that HPV infection takes place mainly later in life.

Adolescent↗
PubMed1997

Sexually transmitted infection as a cause of anal cancer.

BACKGROUND: The incidence of anal cancer has increased in recent decades, particularly among women. To identify underlying risk factors, we conducted a population-based case-control study in Denmark and Sweden. METHODS: We conducted telephone interviews with 324 women and 93 men in whom invasive or in situ anal cancer was diagnosed between 1991 and 1994, 534 controls with adenocarcinoma of the rectum, and 554 population controls. The interviews covered a wide spectrum of possible risk factors for anal cancer. Odds ratios were calculated by logistic regression. Specimens of anal-cancer tissue and samples of rectal adenocarcinomas were tested for human papillomavirus (HPV) DNA with the polymerase chain reaction. RESULTS: Multivariate analysis revealed consistent and statistically significant associations between measures of sexual promiscuity and the risk of anal cancer in both men and women. There was a significant trend toward an association between higher numbers of partners of the opposite sex in women (P<0.001) and men (P<0.05) and strong associations with a variety of venereal diseases. In women, receptive anal intercourse, particularly before the age of 30 years, and venereal infections in the partner were also associated with an increased risk (odds ratios, 3.4 and 2.4, respectively). Fifteen percent of the men with anal cancer reported having had homosexual contact, as compared with none of the controls (P<0.001). High-risk types of HPV, notably HPV-16, were detected in 84 percent of the anal-cancer specimens examined, whereas all rectal-adenocarcinoma specimens tested were negative for HPV. CONCLUSIONS: Our study provides strong evidence that a sexually transmitted infection causes anal cancer. The presence of high-risk types of HPV, notably HPV-16 (which is known to cause cancer of the cervix), in the majority of anal-cancer tissue specimens suggests that most anal cancers are potentially preventable.

Adult↗
PubMed1997

Time since childbirth and prognosis in primary breast cancer: population based study.

OBJECTIVE: To investigate whether time since birth of last child was of prognostic importance in women with primary breast cancer. DESIGN: Retrospective cohort study based on a population based database of breast cancer diagnoses with detailed information on tumour characteristics, treatment regimens, reproductive factors, and vital status. SETTING: Denmark. SUBJECTS: 5652 women with primary breast cancer aged 45 years or less at the time of diagnosis. MAIN OUTCOME MEASURES: 5 and 10 year survival; relative risk of dying. RESULTS: Women diagnosed in the first 2 years after last childbirth had a crude 5 year survival of 58.7% and 10 year survival of 46.1% compared with 78.4% and 66.0% for women whose last childbirth was more than 2 years before their diagnosis. After adjustment for age, reproductive factors, and stage of disease (tumour size, axillary nodal status, and histological grading), a diagnosis sooner than 2 years since last childbirth was significantly associated with a poor survival (relative risk 1.58, 95% confidence interval 1.24 to 2.02) compared with women who gave birth more than 5 years previously. Further analyses showed that the effect was not modified by age at diagnosis, tumour size, and nodal status. CONCLUSIONS: A diagnosis of breast cancer less than 2 years after having given birth is associated with a particularly poor survival irrespective of the stage of disease at debut. Therefore, a recent pregnancy should be regarded as a negative prognostic factor and should be considered in counselling these patients and in the decisions regarding adjuvant treatment.

Adult↗
PubMed1997

Birth order, sibship size and risk of Hodgkin's disease in children and young adults: a population-based study of 31 million person-years.

It has been proposed that Hodgkin's disease (HD) may have an infectious origin and that delayed exposure to infection may increase the risk of HD in young adults. This hypothesis is addressed by studying the family structure among children and young adults. The Civil Registration System was used to establish a population-based cohort consisting of all persons whose mothers were born in Denmark since 1935. Persons who developed HD were identified by linkage with the Danish Cancer Registry. HD incidence rate ratios were estimated based on a log-linear Poisson regression model. The cohort of 2.1 million persons (aged 0-42 years) was followed for 31.1 million person years, during which period 378 cases of HD occurred. Among children (< 15 years, n = 72), the relative risk (RR) of HD tended to increase with increasing sibship size, the relative increase in risk per increase in sibship size (the trend) being 1.28 [95% confidence interval (CI) 1.00-1.63]. The trend for birth order was 1.26 (95% CI 0.92-1.73). Among young adults (> or = 15 years, n = 306) the risk of HD, on the contrary, tended to decrease with increasing sibship size [trend = 0.91 (95% CI, 0.81-1.03)] and birth order (trend = 0.85 (95% CI, 0.71-1.01). These trends among young adults were significantly different from the corresponding trends among children (p < 0.05). Siblings of cases were at increased risk of HD (RR = 18; 95% CI, 2.2-65, n = 2). Our findings are compatible with the hypothesis that delayed exposure to infection may be a risk factor for HD in young adults, and that early exposure perhaps to another infectious agent may increase the risk of HD in children.

Adolescent↗
PubMed1997

HIV-2 genetic variation and DNA load in asymptomatic carriers and AIDS cases in Guinea-Bissau.

The purpose of this study was to document which genetic subtypes of HIV-2 are present in Guinea-Bissau and to investigate whether asymptomatic HIV-2 carriers and AIDS patients carry distinct genetic variants. A secondary aim was to correlate proviral DNA load to clinical and immunologic status of the patients. Thirty-eight asymptomatic HIV-2 carriers and 11 AIDS patients from Bissau, Guinea-Bissau were included in a cross-sectional study in which HIV-2 env V3 sequences, HIV-2 DNA load, and CD4-positive (CD4+) lymphocyte counts were determined. Phylogenetic analyses showed that all investigated subjects carried subtype A HIV-2 variants and that the sequences from AIDS patients and asymptomatic carriers did not form distinct subclusters in the tree. As expected, patients with AIDS had significantly higher median HIV-2 DNA load than did asymptomatic carriers (4.6 vs. 2.0 log10 HIV-2 DNA copies/10(6) CD4+ lymphocytes). Our study indicates that the HIV-2 epidemic in Guinea-Bissau is almost exclusively caused by subtype A HIV-2 variants and that the HIV-2 infections among the asymptomatic carriers and AIDS cases included in the study do not have distinct epidemiologic histories.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Should women be advised against pregnancy after breast-cancer treatment?

BACKGROUND: Oestrogen is an established growth factor in breast cancer. There has, therefore, been much discussion about whether women should be advised against becoming pregnant after breast-cancer treatment because of a possible negative prognostic effect from the high oestrogen concentrations associated with pregnancy. METHODS: We studied 5725 women with primary breast cancer. Information on these women was obtained from the Danish Breast Cancer Cooperative Group. Since 1977 this group has collected population-based data on tumour characteristics, treatment regimens, and follow-up status of Danish women with breast cancer. Details of reproductive history were obtained from The Danish Civil Registration System, the National Birth Registry, and the National induced Abortion registry. We estimated the relative risk of death among women who became pregnant after breast-cancer treatment compared with women who had not become pregnant. FINDINGS: 5725 women with primary breast cancer aged 45 years of younger at the time of diagnosis were followed up for 35,067 patient-years. Among these, 173 women became pregnant after treatment of breast cancer. Women who had a full-term pregnancy after breast-cancer treatment had a non-significantly reduced risk of death (relative risk 0.55 [95% CI 0.28-1.06]) compared with women who had had no full-term pregnancy after adjustment for age at diagnosis, stage of disease (tumour size, axillary nodal status, and histological grading), and reproductive history before diagnosis. The effect was also not significantly modified by age at diagnosis, tumour size, nodal status, or reproductive history before diagnosis of breast cancer. Neither miscarriages nor induced abortions after breast-cancer treatment influenced the prognosis. INTERPRETATION: We found no evidence that a pregnancy after breast-cancer treatment increased the risk of a poor outcome.

Abortion, Induced↗
PubMed1997

Birth characteristics, sibling patterns, and acute leukemia risk in childhood: a population-based cohort study.

BACKGROUND: The occurrence of acute lymphoblastic leukemia (ALL) and acute myeloid leukemia (AML) during childhood may be influenced by factors operating in fetal life. Furthermore, childhood ALL has been suggested to be linked to patterns of infection during infancy. PURPOSE: To explore these hypotheses and other associations, we studied the impact of sibling patterns (e.g., birth order) and birth characteristics (e.g., birth weight) on the risk of childhood ALL and AML. METHODS: By linkage of records of population-based registries, a cohort of all children whose mothers were born in Denmark from April 1935 through March 1978 was established. Children who developed ALL or AML during the period from April 1968 through December 1992 were identified by linkage with the Danish Cancer Registry. Birth weights were obtained for children born during the period from January 1973 through December 1992 by linkage with the Medical Birth Registry. RESULTS: The cohort of approximately 2.0 million children was followed for the diagnosis of ALL or AML for 20.9 million person-years. A total of 704 cases of childhood ALL were identified. Among 0-4 year olds, the relative risks (RRs) of ALL for birth order positions 1, 2, 3, and 4+ were 1.00 (reference), 0.85 (95% confidence interval [CI] = 0.68-1.07), 0.91 (95% CI = 0.66-1.25), and 0.57 (95% CI = 0.30-1.06), respectively (P for trend = .09). A decreasing trend was not observed among 5-14 year olds. A significant log-linear association between birth weight and the risk of ALL was observed for both age groups. Overall, the RR of ALL increased by a factor of 1.46 (95% CI = 1.18-1.81) (P = .0005) for each kilogram of increase in birth weight. A total of 114 cases of childhood AML were identified. Children born second or later in the birth order had an increased risk of AML (RR = 1.53; 95% CI = 1.01-2.32) compared with firstborns. A particularly high risk of AML at ages 2 (RR = 2.53; 95% CI = 1.46-4.40) and 3 years was associated with having siblings compared with being an only child at those ages. Similar to the findings for ALL risk, there was a significant association between birth weight and AML risk. The relative increase in AML risk per 1-kg increase in birth weight was 2.14 (95% CI = 1.19-3.85; P = .009). CONCLUSION AND IMPLICATIONS: The association between birth weight and childhood leukemia suggests the importance of intrauterine factors. A plausible explanation may be that increasing birth weight is associated with a higher rate of cell proliferation and/or a larger number of precursor cells being at risk of malignant transformation. The inverse association between birth order and ALL risk among 0-4 year olds was weak, but it was compatible with the hypothesis that delayed exposure to infection may increase the risk of ALL in this age group. The association of childhood AML with birth order and sibship size at young ages deserves further attention in the search for environmental factors that affect childhood AML risk.

Acute Disease↗
PubMed1997

[Marked increase in incidence of non-Hodgkin's lymphoma among young people in Denmark during 1943-1989].

Time related trends in incidence of non-Hodgkin's lymphoma in Denmark in the period 1943-1989 were analysed. A total of 13,822 patients were included in the study. World standardized incidence rates per 100,000 population increased from 2.5 in men and 1.9 in women in 1943-1947 to 9.3 in men and 6.5 in women in 1988-1989. Trends in age-specific incidence were analysed for two periods, i.e. 1943-1977 and 1978-1989. In both periods, the incidence of NHL increased in all age-groups. In general, the rate of increase was higher in the recent period, with the exception of the oldest age-group among whom the incidence increased by 7% annually between 1943 and 1962. In recent years an increase in incidence averaging 8% annually was observed in men and women aged 40 to 49 years. The remarkable and parallel time trends observed in young men and women in recent years indicate that factors other than AIDS must be contemplated.

Adolescent↗
PubMed1997

Progression to acquired immunodeficiency syndrome is influenced by CD4 T-lymphocyte count and time since seroconversion.

Progression to acquired immunodeficiency syndrome (AIDS) among persons infected with human immunodeficiency virus (HIV) varies considerably and may be influenced by factors such as age, smoking, number of male partners per year, and CD4 T-lymphocyte count. The loss of CD4 lymphocytes is known to be the dominant factor in the progression to AIDS. However, it is unclear whether the effect of the CD4 lymphocyte count is of such importance that persons with similar CD4 cell counts who have been infected for widely different lengths of time have the same risk of AIDS. While a CD4 count is easily obtainable, the precise amount of time since HIV infection is in most circumstances difficult to assess. In the present analysis, 259 Danish and 245 American homosexual men were followed for up to 14 years from 1981 to 1995. Two hundred and one persons seroconverted during the study period, and 112 had developed AIDS before the end of follow-up. CD4 lymphocyte count was highly correlated with the risk of developing AIDS (p < 0.001), but AIDS risk was not affected significantly by either age at infection, smoking, or number of male partners per year (p > 0.20 in all cases). Controlled for CD4 lymphocyte count, time since seroconversion was significant in explaining the risk of AIDS (p = 0.018), with a lower risk being seen during the first 3 years after seroconversion but no effect thereafter. These data confirm the central importance of CD4 lymphocyte level in the progression of HIV disease to AIDS, and suggest that rapid progression within 3 years of infection may be related to factors other than CD4 cell count.

Acquired Immunodeficiency Syndrome↗
PubMed1997

9-year HIV-2-associated mortality in an urban community in Bissau, west Africa.

BACKGROUND: Community studies with 1-3 years of follow-up have reported four to five times higher mortality in HIV-2-infected than in uninfected adults. In a cohort study of HIV-1, an increasing difference in mortality rates of HIV-1-infected and uninfected individuals is expected over time, because of rising mortality with advancing HIV-1 infection. We therefore investigated long-term survival of HIV-2-infected adults. METHODS: Adults enrolled in 1987 in a community study of HIV-2 infection in Guinea-Bissau were followed up with serological surveys in 1989 and 1992. Survival was assessed in 1995, 9 years after enrollment. FINDINGS: The annual incidence of HIV-2 was 0.7% for adults and tended to be higher for older individuals than for participants aged 15-44 years (relative risk 3.21 [95% CI 0.91-11.37]). With control for age, HIV-2-infected adults had twice as high mortality as uninfected individuals (mortality ratio 2.32 [1.18-4.57]); the mortality ratio was highest in the first year of the study (4.50 [1.31-15.43]). The difference between infected and uninfected individuals was stronger for adults under 45 years of age (mortality ratio 4.72 [1.86-11.97]) than for older people (1.35 [0.51-3.56]). HIV-2-infected individuals living with an infected spouse had significantly higher mortality than HIV-2-infected individuals living with an uninfected spouse (p = 0.027). INTERPRETATION: HIV-2-associated mortality is not increasing with length of follow-up. Mortality in HIV-2-infected adults is only twice as high as that in uninfected individuals. In the majority of adults, HIV-2 has no effect on survival.

Acquired Immunodeficiency Syndrome↗
PubMed1997

Population based study of rates of multiple pregnancies in Denmark, 1980-94.

OBJECTIVE: To study trends in multiple pregnancies not explained by changes in maternal age and parity patterns. DESIGN: Trends in population based figures for multiple pregnancies in Denmark studied from complete national records on parity history and vital status. POPULATION: 497,979 Danish women and 803,019 pregnancies, 1980-94. MAIN OUTCOME MEASURES: National rates of multiple pregnancies, infant mortality, and stillbirths controlled for maternal age and parity. Special emphasis on primiparous women > or = 30 years of age, who are most likely to undergo fertility treatment. RESULTS: The national incidence of multiple pregnancies increased 1.7-fold during 1980-94, the increase primarily in 1989-94 and almost exclusively in primiparous women aged > or = 30 years, for whom the adjusted population based twinning rate increased 2.7-fold and the triplet rate 9.1-fold. During 1989-94, the adjusted yearly increase in multiple pregnancies for these women was 19% (95% confidence interval 16% to 21%) and in dizygotic twin pregnancies 25% (21% to 28%). The proportion of multiple births among infant deaths in primiparous women > or = 30 years increased from 11.5% to 26.9% during the study period. The total infant mortality, however, did not increase for these women because of a simultaneous significant decrease in infant mortality among singletons. CONCLUSIONS: A relatively small group of women has drastically changed the overall national rates of multiple pregnancies. The introduction of new treatments to enhance fertility has probably caused these changes and has also affected the otherwise decreasing trend in infant mortality. Consequently, the resources, both economical and otherwise, associated with these treatments go well beyond those invested in specific fertility enhancing treatments.

Adult↗
PubMed1997

Pregnancy and risk of non-Hodgkin's lymphoma: a prospective study.

The etiology of non-Hodgkin's lymphomas (NHL), including chronic lymphocytic leukemia (CLL), is likely to be related to immune function. In the light of the established immunologic effects of a pregnancy, we decided to examine the risk of NHL and CLL in relationship to full-term pregnancies. Within a nationwide cohort we identified 1,546 women with NHL and 198 women with CLL, all 15 years or older, born 1925-1972. Five age-matched controls were selected for each case patient. Conditional logistic regression was used to estimate the odds ratios after mutual adjustment for number of births and age at first birth. We found a weak, negative association between parity and risk of NHL (p for trend 0.11) and a transient, 10-40% decrease in risk within 5-14 years after the last birth among women with various parity status. The risk of CLL decreased more markedly, and orderly with increasing parity, but the trend was not significant (p = 0.18). Small numbers of cases with CLL prevented more detailed analyses of temporal relationships. Age at first birth appeared unrelated to the risk of both NHL and CLL. We conclude that the immunologic alterations associated with a pregnancy have limited, if any, relevance to the etiology of NHL and CLL; changing reproductive pattern is an unlikely contributor to the marked increase in incidence of NHL seen in many populations.

Adult↗
PubMed1997

Induced abortion and the risk of breast cancer.

BACKGROUND: It has been hypothesized that an interrupted pregnancy might increase a woman's risk of breast cancer because breast cells could proliferate without the later protective effect of differentiation. METHODS: We established a population-based cohort with information on parity and vital status consisting of all Danish women born from April 1, 1935, through March 31, 1978. Through linkage with the National Registry of Induced Abortions, information on the number and dates of induced abortions among those women was combined with information on the gestational age of each aborted fetus. All new cases of breast cancer were identified through linkage with the Danish Cancer Registry. RESULTS: In the cohort of 1.5 million women (28.5 million person-years), we identified 370,715 induced abortions among 280,965 women (2.7 million person-years) and 10,246 women with breast cancer. After adjustment for known risk factors, induced abortion was not associated with an increased risk of breast cancer (relative risk, 1.00; 95 percent confidence interval, 0.94 to 1.06). No increases in risk were found in subgroups defined according to age at abortion, parity, time since abortion, or age at diagnosis of breast cancer. The relative risk of breast cancer increased with increasing gestational age of the fetus at the time of the most recent induced abortion: <7 weeks, 0.81 (95 percent confidence interval, 0.58 to 1.13); 7 to 8 weeks, 1.01 (0.89 to 1.14); 9 to 10 weeks, 1.00 >12 weeks, 1.38 (1.00 to 1.90) (reference category, 9 to 10 weeks). CONCLUSIONS: Induced abortions have no overall effect on the risk of breast cancer.

Abortion, Induced↗
PubMed1997

Cancer and diabetes--a follow-up study of two population-based cohorts of diabetic patients.

OBJECTIVES: To study the occurrence of cancer amongst patients with diabetes mellitus (DM). DESIGN: Population based cohort study. SETTING: Denmark. SUBJECTS: Two cohorts of patients with DM were identified. One cohort comprised 1659 conscripts diagnosed with type I DM before the age of 20 years. Another cohort comprised 1499 men and women with insulin treated DM identified by means of medical prescriptions on 1 July 1973. Both cohorts were followed until the end of 1992. MAIN OUTCOME MEASURES: The relative risk of cancer in the two cohorts was estimated as the ratio of observed to expected number of cancers in the cohort (SIR). RESULTS: No unusual risk of cancer was observed amongst the conscripts (SIR 0.9, n = 13) or amongst patients with onset of DM before the age of 30 years in the prescription cohort (SIR 0.9, n = 32). Amongst those aged 30 years or more at DM onset in the prescription cohort, the overall risk of cancer did not depart from normal (SIR 1.0, n = 103), however, pancreatic cancer occurred in excess both immediately (< 1 year) (SIR 190, n = 1), and during 1-9 years after DM onset (SIR 9.0, n = 4). Similarly, the risk of non-Hodgkin's lymphoma was increased significantly (SIR 3.3, n = 6), all cases occurring more than 10 years after DM onset. CONCLUSIONS: Our data suggest that there is no unusual risk of cancer associated with type I DM. Type II DM may be the first symptom of pancreatic cancer and may be associated with an increased risk of non-Hodgkin's lymphoma.

Adult↗
PubMed1997

Cancer risk in a cohort of Danes working in Greenland.

Greenland is a high-incidence area for certain virus-associated cancers. The long term cancer risk in a cohort of 7,761 Danish employees who had been working for some time (median 19.7 months) in Greenland during the period 1955-1978 was studied. During a total of 162,300 person-years (average 20.9 years) of follow-up ending on December 31, 1992, the number of cancers observed was 732 vs. 669 expected (relative risk (RR) = 1.09, 95% confidence interval (CI) 1.02-1.18). Whereas the men did not experience any unusual cancer incidence at any cancer site, the women were at elevated risk of developing breast cancer (RR = 1.5, 95% CI 1.2-1.8 (n = 96)); malignant melanoma (RR = 1.8, 95% CI 1.0-2.9 (n = 16)); and lymphatic and hematopoietic malignancies (RR = 1.7, 95% CI 1.0-2.8 (n = 16)). Exposure during adulthood to a high-incidence area for cervical cancer, nasopharyngeal carcinoma and tumors of the major salivary glands did not confer any measurable increase in the risk for these virus-associated cancers. Postponement of childbearing might explain part of the elevated breast cancer risk. Intensive exposure to ultraviolet light, that is likely to explain the increased risk of malignant melanoma among the women, might also be involved in the excess incidence of lymphatic and hematopoietic malignancies observed in these women. However, why the men did not experience similar alterations in the risk of melanoma and cancers of the immune system is enigmatic.

Adolescent↗