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Biomedical subjects

M Melbye

Publications and source records attributed to M Melbye.

At least 37 records · Page 2Linked to original sources

[Should all younger patients with breast cancer be offered adjuvant cytotoxic chemotherapy?].

The aim of the study was to investigate whether young age at diagnosis is a negative prognostic factor in primary breast cancer and how stage of disease at diagnosis and treatment may influence such an association. It was conducted as a retrospective cohort study based on a population-based data-base of breast cancer diagnosis with detailed information on tumour characteristics, treatment regimens, and vital status and included 10,356 patients with primary breast cancer less than 50 years of age at diagnosis. The main outcome measures were relative risk of dying within the first ten years after diagnosis according to age at diagnosis, adjusted for effect of known prognostic factors and expected mortality. Overall, young patients with low risk disease who did not receive adjuvant treatment had a significantly increasing risk of dying with decreasing age at diagnosis (adjusted relative risk: 45-49 years: 1 (reference); 40-44 years: 1.12 (0.89-1.40); 35-39 years: 1.40 (1.10-1.78); < 35 years: 2.18 (1.64-2.89). However, a similar trend was not seen in young patients who received adjuvant cytotoxic therapy. We found the same difference as above when comparing women receiving no treatment with those receiving adjuvant cytotoxic therapy within strata of node negative patients and patients with the same tumour size. In conclusion, the negative prognostic effect of young age is almost exclusively seen in women diagnosed with low risk disease not receiving adjuvant cytotoxic therapy, whereas young women who receive adjuvant cytotoxic therapy have the same prognosis as middle-aged women. These results suggest that young women with breast cancer, on the basis of age alone, should be regarded as high risk patients and be given adjuvant cytotoxic therapy.

Adult↗

Non-melanoma skin cancer may be a marker of poor prognosis in patients with non-Hodgkin's lymphoma.

According to recent results, patients with non-melanoma skin cancers are at increased risk of developing non-Hodgkin's lymphoma (NHL). The prognostic significance of this association is unknown. Two cohorts of patients with a first diagnosis of non-melanoma skin cancer and a subsequent diagnosis of either NHL (n = 170) or colon cancer (n = 435) were established using national cancer registry data in Denmark. Two other cohorts of patients in whom NHL (n = 600) or colon cancer (n = 1,541) was the patients' first known malignancy served as comparison groups. Mortality rates were compared using Cox's regression analysis. Among patients younger than 80 years at NHL diagnosis, a history of non-melanoma skin cancer was associated with significantly increased mortality [relative risk (RR) = 1.54; 95% confidence interval: 1.19-1.99]. This association was present in both men (RR = 1.38; 1.02-1.86) and women (RR = 2.15; 1.31-3.54) and was similar after both major subtypes of non-melanoma skin cancer. Overall, antedating non-melanoma skin cancer had no prognostic significance for colon cancer patients (RR = 1.00; 0.84-1.18). Whatever the underlying mechanism, our observation has potential clinical implications. If substantiated in other settings, NHL patients with prior non-melanoma skin cancer may constitute a subgroup of lymphoma patients in need of particular therapeutic attention.

Adult↗

Factors influencing the effect of age on prognosis in breast cancer: population based study.

OBJECTIVE: To investigate whether young age at diagnosis is a negative prognostic factor in primary breast cancer and how stage of disease at diagnosis and treatment influences such an association. DESIGN: Retrospective cohort study based on a population based database of patients with breast cancer containing detailed information on tumour characteristics, treatment regimens, and survival. SETTING: Denmark. SUBJECTS: 10 356 women with primary breast cancer who were less than 50 years old at diagnosis. MAIN OUTCOME MEASURES: Relative risk of dying within the first 10 years after diagnosis according to age at diagnosis after adjustment for known prognostic factors and expected mortality. RESULTS: Overall, young women with low risk disease who did not receive adjuvant treatment had a significantly increased risk of dying; risk increased with decreasing age at diagnosis (adjusted relative risk: 45-49 years (reference): 1; 40-44 years: 1.12 (95% confidence interval 0.89 to 1.40); 35-39 years: 1.40 (1.10 to 1.78); <35 years: 2.18 (1.64 to 2.89). However, no similar trend was seen in patients who received adjuvant cytotoxic treatment. The increased risk in younger women who did not receive adjuvant treatment compared with those who did remained when women were grouped according to presence of node negative disease and by tumour size. CONCLUSION: The negative prognostic effect of young age is almost exclusively seen in women diagnosed with low risk disease who did not receive adjuvant cytotoxic treatment. These results suggest that young women with breast cancer, on the basis of age alone, should be regarded as high risk patients and be given adjuvant cytotoxic treatment.

Adult↗

Correlates of heterosexual behavior among 23-87 year olds in Denmark and Sweden, 1992-1998.

Correlates of heterosexual behavior, with a particular focus on early and high sexual activity, anal intercourse, prostitute visits, and HIV test activity, were studied. Telephone interviews were conducted with 852 randomly chosen persons who participated as controls in nationwide case-control studies of anogenital cancers in Denmark and Sweden, 1992-1998. While partner numbers and the practice of anal intercourse increased, age at sexual debut declined by 4-5 years (p < 0.001) and the maturation interval between menarche and first coitus halved (from 7 to 3 years, p < 0.001) between persons born in or before 1920 and those born in or after 1960. Women having high sexual activity were more often tested for HIV than less sexually active women, but men visiting prostitutes and those with prior STDs were not HIV tested more than other men. The increasing practice of anal intercourse, particularly among women with many partners, deserves attention, since this practice may erroneously be considered a safe sexual activity. Along with their partners, men with a history of STDs and those visiting prostitutes should be targeted in future safe sex campaigns, since these men appear to be inadequately HIV tested.

Adult↗

Multiple sclerosis and poliomyelitis. A Danish historical cohort study.

OBJECTIVE: To evaluate whether persons with a history of poliomyelitis are at an increased risk of developing multiple sclerosis (MS). MATERIAL AND METHODS: All patients diagnosed with acute poliomyelitis in the greater capital area of Copenhagen, Denmark, between 1919 and 1954 were identified and followed with respect to MS. Information on vital status and diagnosis of sclerosis was obtained through linkage with the Danish Civil Registration System and The Danish Multiple Sclerosis Registry, respectively. Follow-up started on the date of the establishment of the Danish Civil Registration System (April 1, 1968) until death, emigration or December 31, 1996, whichever came first. The observed incidence of MS among polio patients was compared with the expected incidence calculated according to national gender, age and period specific rates of MS. RESULTS: During 149,364 years of follow-up, 19 cases of multiple sclerosis were observed among 5652 polio patients compared with 11.0 expected (SIR = 1.73 (1.04-2.74)). The increased risk of MS was most pronounced in polio patients hospitalized during adolescence. Neither gender nor the acute severity of poliomyelitis modified the risk of MS. CONCLUSION: Our results are based on small numbers of events, however the findings suggest that the polio patients might be at an increased risk of MS.

Adult↗

Gender of offspring and long-term maternal breast cancer risk.

Gender of offspring is influenced by maternal hormonal level during pregnancy, which is believed to influence the subsequent maternal breast cancer risk. However, analysing national birth and cancer registrations in a cohort of 998,499 women, we found no association between gender of offspring and subsequent breast cancer risk.

Adult↗

Incidence patterns of lyme disease and cutaneous B-cell non-Hodgkin's lymphoma in the United States.

BACKGROUND: Several reports have suggested a link between infection with Borrelia burgdorferi (the spirochete causing Lyme disease) and development of cutaneous B-cell non-Hodgkin's lymphoma (CBCL). METHODS: We did a correlation analysis of CBCL and Lyme disease using data from the Surveillance, Epidemiology and End Results program and from the Centers for Disease Control and Prevention. RESULTS: We could not demonstrate a geographic correlation between incidence rates of Lyme disease and CBCL. CONCLUSION: This observation suggests that infection with B. burgdorferi is not a major risk factor for CBCL in the USA.

Borrelia burgdorferi Group↗

Reproductive history and stage of breast cancer.

A woman's reproductive history influences her risk of breast cancer. The authors hypothesized that reproductive history also influences stage of disease at the time of diagnosis. The authors analyzed a population-based cohort of 1.5 million Danish women born between 1935 and 1978 for whom individual information on births was available. Between 1978 and 1994, 10,790 incident cases of breast cancer in women under 60 years of age were identified. Nulliparous women compared with parous women and women with a late age at first birth compared with an early age were at significantly increased risk of being diagnosed with a large tumor and with cancer that had spread to regional lymph nodes. However, such an association was not seen for women diagnosed with a small tumor and women with cancer that had not spread to regional lymph nodes. Reproductive history did not appear to influence the time interval from first symptoms to first physician visit ("patient delay") or the time interval from first physician visit to surgery ("doctor delay"). The authors conclude that reproductive history is associated both with incidence of breast cancer and with stage of the disease at diagnosis, indicating possible influences on tumor progression and growth rate. Intensified awareness is warranted to achieve earlier diagnosis among nulliparous women and women with a late age at first childbirth, with the hope of improving their prognosis.

Adult↗

Is history of squamous-cell skin cancer a marker of poor prognosis in patients with cancer?

BACKGROUND: Nonmelanoma skin cancer is associated with increased occurrence of subsequent cancer and death from cancer, but it is not known whether a history of skin cancer is associated with poor prognosis after a second diagnosis of cancer. OBJECTIVE: To determine whether history of squamous-cell skin cancer is a marker of poor prognosis in patients with cancer. DESIGN: Population-based cohort study. SETTING: Sweden, 1958 to 1996. PATIENTS: All patients in the Swedish Cancer Registry with or without a first diagnosis of squamous-cell skin cancer and a subsequent or first diagnosis of non-Hodgkin lymphoma (including chronic lymphocytic leukemia) or cancer of the colon, breast, prostate, or lung. MEASUREMENTS: Relative risk (RR) for death determined by using Cox proportional hazards regression analysis. RESULTS: Patients with a history of squamous-cell skin cancer had a significantly greater risk for death than those with no such history after receiving a diagnosis of non-Hodgkin lymphoma (RR, 1.33), colon cancer (RR, 1.24), breast cancer (RR, 1.19), or prostate cancer (RR, 1.17). Patients with lung cancer and a history of squamous-cell skin cancer who survived for 1 year after diagnosis of lung cancer also had an increased risk for death (RR, 1.29). CONCLUSION: Patients with a registered history of squamous-cell skin cancer have a poor prognosis after diagnosis of subsequent cancer and warrant careful medical attention.

Adult↗

Sex ratios, family size, and birth order.

In many countries, the male:female ratio at birth has varied significantly over the past century, but the reasons for these changes have been unclear. The authors observed a close parallel between decreasing family size and declining male:female sex ratio in Denmark from 1960 to 1994. To explain this finding, they examined the sex ratio and birth order of 1,403,021 children born to 700,030 couples. Overall, 51.2% of the first births were male. However, families with boys were significantly more likely than expected to have another boy (biologic heterogeneity). By the fourth birth to families with three prior boys, 52.4% were male. The increase varied directly with the number of prior boys (p for trend = 0.0007). Furthermore, couples with boys were more likely to continue to have children. In summary, the authors found that the declining male:female ratio in Denmark and probably other European populations is mainly attributable to three effects: declining family size, biologic heterogeneity, and child sex preference. Why families with boys are more likely to have additional boys is unknown.

Birth Certificates↗

Epstein-Barr virus and cytomegalovirus in relation to testicular-cancer risk: a nested case-control study.

An infectious etiology of testicular cancer has been suggested. We have evaluated seroreactivity against cytomegalovirus (CMV) and Epstein-Barr virus (EBV) in relation to testicular-cancer risk in a case-control study, nested within a cohort of prospectively collected serum specimens from 293,692 individuals. For each of 81 cases of testicular cancer identified, 3 controls were randomly selected from the cohort. Serum IgG antibody titers against CMV and EBV were determined using enzyme-linked immunosorbent assays (ELISAs) and immunofluorescence methods. Odds ratios (OR) were obtained from conditional logistic-regression models. No association was found between CMV positivity and testicular cancer overall (OR = 1.08; 95% confidence interval 0.60-1.94); risk for testicular seminoma was increased among CMV seropositive [OR = 1.70 (0.80-3.59)], whereas seropositivity was associated with decreased risk for testicular non-seminoma [OR = 0.54 (0.19-1.56)] (p for heterogeneity, 0.09). For EBV, the risk for testicular cancer was increased among individuals seropositive for viral capsid antigen (VCA) [OR = 2.74 (0.62-12.12)]. The results lend some support to the hypothesis of an infectious etiology, and we propose that future studies should take into account age at infection.

Adult↗

Multivariate competing risks.

Competing risks models can be used to compare the effect of risk factors for different causes of death or subtypes of a disease. However, sometimes more than one outcome classification is available and if two such classifications are correlated, one may speculate whether differences in the effect of a risk factor according to one classification simply may be an effect of differences according to the other correlated classification. We introduce in this paper the new concept of multivariate competing risks to test formally such a hypothesis.

Breast Neoplasms↗

Smoking and oral contraceptives as risk factors for cervical carcinoma in situ.

Human papillomavirus (HPV) is probably a necessary but definitely not a sufficient cause of cervical carcinoma. However, it remains unclear which factors, in addition to HPV, are important for the development of cervical carcinoma and its precursor lesions. To address this issue, we conducted a case-control study nested in a population-based cohort consisting of women participating in cytological screening in one Swedish county, any time during 1969 through 1995. Detailed information on sexual practice, smoking habits and oral contraceptive (OC) use were collected through telephone interviews with 422 case patients diagnosed with cervical carcinoma in situ and 422 control subjects. All cytological smears were analyzed for presence of HPV 16/18 by a polymerase chain reaction (PCR)-based method. Odds ratios (OR) were used as measures of relative risk. After multivariate adjustment, a 2-fold higher risk was observed among current smokers compared with never smokers [OR 1.94; 95% confidence interval (CI 1.32-2.85)], an association apparently confined to women younger than 45 years. Current use of OCs was associated with a 4-fold increased risk overall (OR 3.64; 95% CI 1.91-6.93) with a monotonic increase with increasing duration of use (p for trend < 0.001). The number of sexual partners was significantly, positively associated with risk among HPV 16/18-negative (p for trend < 0.005) but not among HPV 16/18-positive women. Our data confirm the association between smoking and cervical carcinoma in situ, which might be age-dependent. Our results further indicate a relation with OC use and the risk for cervical carcinoma in situ.

Adult↗

Tobacco smoking as a risk factor in anal carcinoma: an antiestrogenic mechanism?

BACKGROUND: Human papillomavirus-associated anogenital carcinogenesis depends on poorly defined cofactors. Smoking was recently suggested to increase the risk of anal cancer more in premenopausal women than in postmenopausal women. Thus, we used our population-based anal cancer case-control study in Denmark and Sweden to test this hypothesis. METHODS: Our study included 417 patients (324 women and 93 men) who were diagnosed with anal cancer (84% invasive cancer) from 1991 through 1994; it also included five patients diagnosed in 1995. Two control groups were used: 1) 554 population control subjects (349 women and 205 men) and 2) 534 patients with rectal adenocarcinoma (343 women and 191 men). Odds ratios (ORs), calculated from logistic regression analyses, were used as measures of relative risk. All P values are two-sided. RESULTS: Compared with the risk for lifelong nonsmokers, the risk of anal cancer was high among premenopausal women who currently smoked tobacco (multivariate OR = 5.6; 95% confidence interval [CI] = 2.4-12.7) and increased linearly by 6.7% per pack-year smoked (one pack-year is equivalent to one pack of cigarettes smoked per day for 1 year) (P for trend <.001). Smoking was not statistically significantly associated with anal cancer risk in postmenopausal women or men. Women whose menstrual periods started late were at high risk (multivariate OR = 3.6; 95% CI = 1.8-7.3, for > or = 17 years of age versus < or = 12 years of age; P for trend <.001), and body mass index (weight in kg/[height in m]2) was inversely associated with risk among women (P<.001). CONCLUSIONS: Because the risk of anal cancer associated with smoking was restricted to premenopausal women and because higher risk was associated with late menarche and lean body composition, female sex hormones may be a factor in anal cancer development in women. Since the anal mucosa is an estrogen-sensitive area, we hypothesize an antiestrogenic mechanism of action for smoking in anal carcinogenesis.

Adult↗

Reproductive risk factors for breast cancer by receptor status, histology, laterality and location.

It is well established that a woman's reproductive history influences her risk of breast cancer. We examined whether the effect of reproductive history was similar for different sub-types of breast cancer. The study was based on a population-based cohort of 1.5 million Danish women born between 1935 and 1978, with individual information on births. Between 1978 and 1994, 10,790 incident cases of breast cancer were identified in a nationwide cancer registry, including detailed information on receptor status, histology, laterality and location of the tumour. Overall, the incidence of breast cancer was 13% lower in parous compared with nulliparous women. This reduction was significantly stronger for mucinous than for ductal carcinomas and for tumours located centrally than for those non-central in the breast. Overall, the incidence in parous women increased by 10% by each 5-year postponement of their first birth. For the incidence of lobular carcinomas this increase was significantly stronger, and for mucinous carcinomas it tended to be stronger than for ductal carcinomas. For the incidence of centrally located tumours the increase was stronger than for non-centrally located tumours. On average, there was a 10% decrease in breast-cancer risk by each additional birth. This decrease was seen in most sub-types, but not for lobular carcinomas of for centrally located tumours. According to our findings, lobular and mucinous carcinomas and centrally located tumours may have risk-factor profiles that differ from other types of breast cancer.

Adolescent↗

Effects of family history and place and season of birth on the risk of schizophrenia.

BACKGROUND: Although a family history of schizophrenia is the best-established risk factor for schizophrenia, environmental factors such as the place and season of birth may also be important. METHODS: Using data from the Civil Registration System in Denmark, we established a population-based cohort of 1.75 million persons whose mothers were Danish women born between 1935 and 1978. We linked this cohort to the Danish Psychiatric Central Register and identified 2669 cases of schizophrenia among cohort members and additional cases among their parents. RESULTS: The respective relative risks of schizophrenia for persons with a mother, father, or sibling who had schizophrenia were 9.31 (95 percent confidence interval, 7.24 to 11.96), 7.20 (95 percent confidence interval, 5.10 to 10.16), and 6.99 (95 percent confidence interval, 5.38 to 9.09), as compared with persons with no affected parents or siblings. The risk of schizophrenia was associated with the degree of urbanization of the place of birth (relative risk for the capital vs. rural areas, 2.40; 95 percent confidence interval, 2.13 to 2.70). The risk was also significantly associated with the season of birth; it was highest for births in February and March and lowest for births in August and September. The population attributable risk was 5.5 percent for a history of schizophrenia in a parent or sibling, 34.6 percent for urban place of birth, and 10.5 percent for the season of birth. CONCLUSIONS: Although a history of schizophrenia in a parent or sibling is associated with the highest relative risk of having the disease, the place and season of birth account for many more cases on a population basis.

Adolescent↗