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Biomedical subjects

I Persson

Publications and source records attributed to I Persson.

At least 37 records · Page 2Linked to original sources

Variation in the efficacy of hormone replacement therapy in the prevention of hip fracture. Swedish Hip Fracture Study Group.

Use of postmenopausal hormone replacement therapy (HRT) has been associated with a reduced risk of osteoporotic fractures. However, it is uncertain whether this risk reduction is modified by other risk factors for hip fracture. In a population-based case-control study in Sweden, we investigated the association between HRT and hip fracture risk within categories of age, body measures and lifestyle factors in postmenopausal women, 50-81 years of age. Mailed questionnaires and telephone interviews were used to collect data. Of those eligible, 1328 incident cases with hip fracture (82.5%) and 3312 randomly selected controls (81.6%) answered the questionnaire. Ever use of HRT in women less than 75 years old was associated with an odds ratio (OR) of 0.66 (95% confidence interval: 95% CI 0.50-0.87) for hip fracture compared with OR 0.40 (95% CI 0.21-0.77) in women 75 years or older. We found a significant interaction between HRT and both weight and physical activity (p < 0.05). The protective effect of HRT was particularly pronounced in lean women: compared with never HRT users, ever users weighing under 60 kg had an OR of 0.44 (95% CI 0.30-0.66) whereas women weighing more than 70 kg had an OR of 0.91 (95% CI 0.53-1.56). Women with low recent leisure physical activity (less than 1 h/week) similarly benefited more from HRT for hip fracture prevention than women with a higher degree of recreational physical activity. The observed interactions with weight and physical activity suggest that HRT has the best protective effect against hip fracture among high-risk women.

Age Factors

Association of family history and other risk factors with breast cancer risk (Sweden).

OBJECTIVES: Women with a family history of breast cancer have an increased risk for the disease. However, the combined impact of family history and other risk factors on breast cancer risk is unclear. We conducted a large epidemiologic study to examine this issue. METHODS. In a population-based case-control study in all of Sweden, 3,345 women aged 50 to 74 years with invasive breast cancer (84 percent of all eligible), and 3,454 controls of similar age (82 percent of all selected) were included. Mailed questionnaires and telephone interviews were used to collect detailed information on potential breast cancer risk factors. Odds ratios (OR) and 95 percent confidence intervals (CI) were estimated through multiple logistic regression. RESULTS: Women with a history of breast cancer in any first-degree relative had an increased risk of breast cancer compared with those without such a history (OR = 1.96, CI = 1.67-2.30). There was no clear indication of a differential impact of hormonal risk factors (age at menarche, parity, age at first birth, age at menopause, use of exogenous hormones, and weight gain) or body build at age seven among women with and without a positive family history. Yet, benign breast disease and height clearly were related to breast cancer risk in subjects without a family history, whereas seemingly not so in women with a family history. Formal tests for interaction between family history and these factors, however, did not prove statistically significant. CONCLUSIONS: Our findings indicate that established risk factors entail similar associations with breast cancer risk among women with and without family history of the disease.

Aged

Recent trends in breast cancer incidence in Sweden.

Breast cancer incidence in Sweden during the period 1984-93 shows no clear trend in women aged below 40 years but a transient increase at ages 50-69 years, probably as a result of mammography screening. Our data give no indication that use of oral contraceptives or replacement hormones have affected nationwide breast cancer incidence rates.

Adult

Hormonal aspects of epithelial ovarian cancer: review of epidemiological evidence.

Epithelial ovarian cancer is fairly common with high rates in Scandinavia, intermediate rates in western Europe and North America and low rates in the developing countries and in Japan. The 5-year survival rate is less than 40%. Increasing parity consistently gives a strong protection against epithelial ovarian cancer. A lesser degree of protection is probably derived from incomplete pregnancies and lactation. Ages at menarche and menopause are most probably weak predictors of epithelial ovarian cancer risk. Ever users of oral contraceptives (OC) have 30% lower risk compared to never users. The protection increases with duration of OC use, being about 50% after 5 years. The reduced risk among past OC users persists for at least 10 years after cessation of use. Results concerning hormone replacement therapy (HRT) and epithelial ovarian cancer risk are conflicting, but most data point to a weak or no association, but as an increasing number of women use HRT it still seems important to resolve any potential effect. Infertility adds to epithelial ovarian cancer risk in nulliparous women, while temporary fertility problems in parous women do not appear to increase risk. A possible independent risk effect of fertility drug use has not been easy to assess and remains unresolved. It has been particularly difficult to separate the effects of fertility drugs from those of infertility. Tubal ligation and hysterectomy convey protection against epithelial ovarian cancer, possibly through a suppressed ovarian hormone production. The causes of epithelial ovarian cancer are poorly understood, but reproductive hormones are thought to be involved in the aetiology. For a long time the 'incessant' and 'gonadotrophin' hypotheses have been promoted in relation to carcinogenesis. Both hypotheses find support in ovarian cancer epidemiology, and recent progress in molecular biology adds to the understanding of possible aetiological mechanisms. Another hypothesis focuses on the retrograde transport of contaminants or carcinogens through the Fallopian tubes. It is important to establish if the same risk factors apply to the various histological types of ovarian cancer, as particularly the mucinous ovarian tumours seem to present with different risk factors. Another question to resolve is if sporadic vs. inherited cases carry distinct risk profiles. As the hypotheses above do not explain all of the results derived from ovarian cancer epidemiology, there is a need to test additional hypotheses to possibly define preventive programmes and to come closer to the cause of ovarian cancer.

Adenocarcinoma

Oral contraceptive use: interview data versus pharmacy records.

BACKGROUND: If women tend to forget and underreport their past oral contraceptive (OC) use, but the recall among cases is enhanced by the presence of disease, recall bias may explain some reported health effects of OC use. METHODS: Two different sources of information on lifetime OC use were compared for 427 (84%) of a community-based sample of 511 women aged 20-34: (i) structured interviews, using a life event calendar and picture display as memory aids, and (ii) a register of all prescriptions dispensed by pharmacies in the county since 1970. RESULTS: Interview data and pharmacy records showed high levels of agreement for any OC use, current use, time since first and last use, total duration of use, and for duration of use in different 'time windows'. But there was a tendency to under-report specific kinds of OC used in the past. CONCLUSION: Underreporting of OC use among non-cases would usually introduce little or no bias (as compared to pharmacy records) for this kind of interview and women. However, it may be preferable to use interviews for current OC use, and pharmacy records for specific kinds of OC used in the past.

Adult

Hormone replacement therapy and the risk of breast cancer. Nested case-control study in a cohort of Swedish women attending mammography screening.

There is concern that hormone replacement therapy (HRT) increases the risk of breast cancer. We undertook a case-control study of this risk relationship within a cohort of 40- to 74-year-old women in Uppsala County, Sweden, who participated in mammography screening. Incident cases of breast cancer were ascertained during 5 years of follow-up. In all, 435 cases (87% invasive, 13% in situ cancers) were detected, 313 through screening and 122 through clinical diagnosis. As controls, 1,740 women were selected randomly. Information on risk factors and use of HRT was obtained through interviews before the start of follow-up. Multivariate analyses revealed an increased risk among users of any type of HRT for more than 10 years, the odds ratio (OR) being 2.1 (95% confidence interval [CI] 1.1-4.0), as well as when restricting analyses to cases diagnosed through mammography screening. After stratification for compound type, risk estimates were apparently higher among women reporting estradiol-progestin combined treatment vs. estradiol or conjugated estrogens alone, with ORs for more than 10 years of intake being 2.4 (95% CI 0.7-8.6) and 1.3 (95% CI 0.5-3.7), respectively. Analyses through a model including both compound type and length of hormone intake confirmed a significant excess risk linked to treatment for more than 10 years, OR = 2.6 (95% CI 1.3-5.1). Our results indicate a moderately increased risk of breast cancer after many years of HRT and, hypothetically, a further enhancement of the risk with added progestins.

Adult

Risk of endometrial and breast cancer in patients with diabetes mellitus.

Diabetes mellitus patients have metabolic and endocrine alterations that could contribute to an increased incidence of hormone-related cancers. We assessed the incidence of endometrial and breast cancer among 80,005 women and the incidence of breast cancer among 73,847 men (total of 153,852 patients) identified in the Swedish In-patient Register as having been hospitalized for diabetes mellitus in the period 1965-1983. These patients underwent follow-up through 1989 via the Swedish Cancer Register and other nation-wide Swedish registers. The outcome measures were standardized incidence ratios (SIR) based on age-, sex- and calendar period-specific incidence rates from the entire Swedish population. To minimise the effect of selection bias, we excluded from the calculation of incidence ratios the first year of observation and cases diagnosed incidentally at autopsy. Only first cancers were considered for the estimates. A total of 328 endometrial cancers (SIR = 1.8; 95% confidence interval [CI] = 1.6-2.0), 1,145 female breast cancers (SIR = 1.3; 95% CI = 1.2-1.4) and 13 male breast cancers (SIR = 2.0; 95% CI = 1.0-3.4) were observed. We conclude that compared with the general population, patients with diabetes mellitus have an increased incidence of endometrial and breast cancers.

Adult

In vitro kinetics of two human CYP1A1 variant enzymes suggested to be associated with interindividual differences in cancer susceptibility.

A genetic polymorphism (A4889-->G) in the human CYP1A1 gene which creates an Ile462-->Val amino acid substitution has been suggested to cause altered enzymatic properties of CYP1A1. Since several epidemiological studies have shown an association between the CYP1A1-Val allele and lung cancer, we considered it of importance to evaluate the in vitro kinetic properties of the two CYP1A1 variants after expression of each cDNA in yeast. No differences were found in K(m) or Vmax for CYP1A1 dependent O-dealkylation of ethoxyresorufin and 3-hydroxylation of benzo(a)pyrene between the two variants. The data indicate that the Ile/Val polymorphism in human CYP1A1 is not functionally important.

Benzo(a)pyrene

Breast cancer risk associated with gynecologic surgery and indications for such surgery.

Risk of breast cancer was assessed in relationship to gynecologic operations using data from a record-linkage study involving 15,844 women in the Uppsala Health Care Region of Sweden, who underwent surgery between 1965 and 1983. Data abstracted from medical records for the breast cancer cases and a random sample of the cohort allowed examination of risk associated with these operations in regard to menopausal status and indications for the operations. Among women who were pre-menopausal at the time of operation, a bilateral oophorectomy before the age of 50 years was associated with a 50% reduction in the risk of breast cancer compared with the background population, a reduction in risk evident within 10 years of the operation. A bilateral oophorectomy after the age of 50 years in pre-menopausal women or after a natural menopause was not associated with any reduction in risk. There were no reductions in risk associated with a unilateral oophorectomy or hysterectomy among women who were pre-menopausal at the time of operation. In fact, hysterectomy alone was associated with a slight increase in breast cancer risk when the operation was due to myomas, abnormal bleeding, and, possibly, severe forms of endometriosis but not to other reasons. Risk did not vary substantially by indications for oophorectomy, including benign ovarian neoplasms and functional ovarian cysts, though endometriosis was associated with a non-significant increase in breast cancer risk.

Adult

Cancer risk after a hospital discharge diagnosis of endometriosis.

OBJECTIVES: Our goal was to determine the risk of cancer after hospitalization for endometriosis. STUDY DESIGN: Records of 20,686 women hospitalized with endometriosis during the period 1969 to 1983, as identified through the nationwide Swedish Inpatient Register, were linked against the National Swedish Cancer Registry through 1989 to identify all subsequent diagnoses of cancer. The study subjects were followed up for a mean of 11.4 years, with the cohort contributing 216,851 woman years of follow-up. Standardized incidence ratios were computed by the use of age- and period-specific incidence rates derived from the Swedish population. Because of the high proportion of subjects with gynecologic operations (55.6%), evaluation of the risk of gynecologic cancers involved truncation of person years at the time of any such operation. RESULTS: The overall cancer risk was 1.2 (95% confidence interval 1.1 to 1.3). Significant excesses were observed for breast cancer (standardized incidence ratio = 1.3, 95% confidence interval 1.1 to 1.4), ovarian cancer (1.9, 1.3 to 2.8), and hematopoietic malignancies (1.4, 1.0 to 1.8); this latter excess was largely driven by an excess risk of non-Hodgkin's lymphoma (1.8, 1.2 to 2.6). The risk of ovarian cancer was particularly elevated among subjects with a long-standing history of ovarian endometriosis (4.2, 2.0 to 7.7). Cervical cancer risk was slightly reduced (0.7, 0.4 to 1.3) whereas no association was observed for cancer of the endometrium (1.1, 0.6 to 1.9). CONCLUSIONS: These findings suggest that further attention be given to the risk of breast, ovarian and hematopoietic cancers among women with endometriosis and to exploring possible hormonal and immunologic reasons for the excess risks.

Breast Neoplasms

Hormone replacement therapy and major risk factors for reproductive cancers, osteoporosis, and cardiovascular diseases: evidence of confounding by exposure characteristics.

Observational studies have yielded reports on long-term effects of hormone replacement therapy (HRT) for cardiovascular, osteoporosis-related, and cancer diseases. There is concern that risk estimates may be confounded by complex mechanisms of selection with regard to important risk determinants. In this study, we tested the hypothesis that baseline characteristics of women vary with exposure characteristics, i.e., the choices of complying with prescriptions, using different compounds and regimens, and continuing intake long-term. We analyzed the prevalence of relevant risk factors and their relationships to characteristics of exposure among 11,211 Swedish women who had received prescription for HRT. Associations were studied through logistic regression, with comparisons of women with ever-use versus non-compliance, long-term (73+ months) versus short-term use (1-72 months), intake of conjugated estrogens versus estradiol compounds, and intake of estrogens only versus estrogens combined with progestins, respectively. We found that women denying intake of using HRT short-term had higher parity, earlier age at first birth and a lower prevalence of hysterectomy or oophorectomy than those complying or exposed long-term. A high level of education was associated with compliance and long-term exposure, and heavy physical exercise and high intake of food fibers were associated with compliance. Climacteric symptoms were associated with compliance, long-term intake and use of conjugated estrogens, whereas a history of oral contraceptive intake was associated with use of estrogens alone without progestins. We conclude that selection biases in studies of HRT effects are important and complex in that they may vary with the reported exposure. Our findings are important, as they point to the need for improved methods for measuring, in particular, factors linked to lifestyle and health behavior, in order to account more fully for confounding in the analyses of risk relationships.

Aged

Risk for endometrial cancer following breast cancer: a prospective study in Sweden.

The risk for endometrial cancer among women with breast cancer might increase following use of tamoxifen, recently classified as a carcinogen of the human endometrium. However, the strength of the association remains uncertain and it is unknown whether use of this drug--widely prescribed in Sweden since the mid-1980s--has had any measurable effect at the population level. We analyzed all cases of breast cancer (n = 131,614) detected in the nationwide Swedish Cancer Registry in 1958-93. Incident cases of endometrial cancer during follow-up were identified also through the Cancer Registry. Standardized incidence ratios (SIR) and their 95 percent confidence intervals (CI) were computed by use of nationwide rates of endometrial cancer, adjusted for age and calendar year. During follow-up of up to 35 years of the breast cancer cohort, 803 incident endometrial cancers were identified, yielding an overall SIR of 1.58 (CI = 1.47-1.70). In univariate analyses, there was no increase in SIR in recent years. However, the excess risk increased linearly with increasing age at breast cancer diagnosis (P trend < 0.0001) and decreased markedly with longer follow-up (P trend < 0.0001). A multivariate regression analysis, with adjustment for age and year of follow-up, revealed no increased risk for subsequent endometrial cancer among breast cancer cases diagnosed more recently (P trend = 0.19); compared with the period 1958-63, the risk estimate in the last time period (1989-93) was 0.72 (CI = 0.51-1.01). We conclude that the risk for endometrial cancer following breast cancer has not increased over time in Sweden.

Adult

Trends in urinary bladder cancer incidence in Sweden 1960-93 with special reference to histopathology, time period, birth cohort, and smoking.

This study investigates the incidence trends of urinary bladder cancer in Sweden from 1960 through 1993 (a total of 46,211 cases). Age-standardized incidence rates increased among men from 14.6 per 10(5) in 1960 to 33.5 in 1993 and among women from 4.8 to 8.8, corresponding to an average annual increase of 2.4 percent (95 percent confidence interval [CI]) = 2.0-2.7 percent) and 1.1 percent (CI = 0.9-1.4 percent), respectively. The largest increase occurred in the oldest age-groups. The proportion of patients with transitional cell carcinoma increased in men from 66.0 percent in 1960-64 to 93.6 percent in 1990-93 and in women from 61.0 percent to 89.4 percent. The proportion of patients with papillomas decreased, whereas those with adenocarcinoma and squamous cell carcinoma were stable. Regression modeling (based on the period 1960-89) showed a strong linear effect due to either period and/or cohort. Among men, additional non-linear effects by both period and cohort were obtained. The cohort effects were more important. Cohort data on having smoked daily showed considerable similarities with the estimated cohort-effects. Our findings suggest that the increase of tobacco smoking in successive generations can explain the increase in incidence rates of bladder cancer in Sweden, whereas improved diagnostic activities and registration are less likely to explain fully the changes in incidence rates.

Adult

Cause-specific mortality in women receiving hormone replacement therapy.

To assess the risks and benefits of menopausal hormone replacement therapy, we followed a 23,346-member, population-based cohort of Swedish women who were prescribed menopausal estrogens for an average of 8.6 years for mortality. Compared with the general population, the standardized mortality ratio for all-cause mortality in this cohort was 0.77 (95% confidence limits = 0.73, 0.81). Deaths in each of the 12 major categories of causes of death except for injuries occurred 12% to 86% less frequently than expected. We examined in detail four specific causes of death according to the type of hormone prescribed, namely weak estrogens (primarily estriol), more potent estrogens (primarily estradiol and conjugated estrogens) in combination with a progestin, and more potent estrogens without a progestin. Mortality from endometrial cancer was not related to the prescription of weak estrogens or an estrogen-progestin combination, but mortality was 40% higher in women prescribed more potent estrogens without a progestin. Women prescribed weak estrogens, more potent estrogens, and the combined estrogen-progestin regimen were at reduced risk of death from ischemic heart disease (standardized mortality ratios of 0.7, 0.6, and 0.4, respectively). The more potent estrogens and the estrogen-progestin combination were associated with a marked reduction in risk of intracerebral hemorrhage (standardize mortality ratios of 0.4 and 0.6, respectively) and "other" cerebrovascular disease, but not other types of stroke. The concern that use of progestins would lead to psychic disorders related to suicide received no support from our results. Breast cancer results are described elsewhere. These data provide little evidence of an adverse effect of the combined estrogen-progestin regimen as compared with estrogens alone on mortality. They do indicate, however, that both selection factors and biology may contribute to the almost across-the-board-reduction in mortality associated with hormone replacement therapy.

Adult

An outbreak of listeriosis suspected to have been caused by rainbow trout.

An outbreak of listeriosis in Sweden, consisting of nine cases, was investigated by means of molecular typing of strains from patients and strains isolated from suspected foodstuffs, together with interviews of the patients. Listeria monocytogenes was isolated from six of the patients, and all isolates were of the same clonal type. This clonal type was also isolated from a "gravad" rainbow trout, made by producer Y, found in the refrigerator of one of the patients. Unopened packages obtained from producer Y were also found to contain the same clonal type of L. monocytogenes. Based on the interview results and the bacteriological typing, we suspect that at least six of the nine cases were caused by gravad or cold-smoked rainbow trout made by producer Y. To our knowledge, this is the first rainbow trout-borne outbreak of listeriosis ever reported.

Aged

Effect of estrogen and estrogen-progestin replacement regimens on mammographic breast parenchymal density.

PURPOSE: Hormone replacement therapy (HRT) may increase the mammographic density with a possible reduction in the sensitivity or specificity. If so, the benefit of mammographic screening in women using HRT could be compromised. We evaluated the hypothesis that HRT regimens have differential effects on the mammographic density depending on treatment regimens or on age. PATIENTS AND METHODS: Among 31,498 Swedish women who received mammographic screening, we selected 554 women who started HRT after the first examination and who were current users at the second, and 554 age-matched women who had never received HRT. Mammograms were examined in a blinded review. The changes in density between the two examinations, graded as moderate or weak reduction, no change, or weak, moderate, or substantial increase, were assessed. We studied four HRT regimens-estradiol compounds only, estradiol compounds cyclically or continuously combined with progestins, and weak estrogens-and used descriptive statistics and logistic regression to analyze the association between HRT and density change. RESULTS: Density increased in 10% and 28% of women who received estradiol compounds with cyclically or continuously combined progestins, respectively, but in only 3% of unexposed women. Logistic regression analyses showed an elevated risk of a density increase (relative risk [RR] = 3.6; 95% confidence interval [CI], 1.6 to 7.7) in women who received cyclically combined regimens or continuously combined regimens (RR = 12.4; 95% CI, 6.3 to 24.4) compared with unexposed women. Women > or = 50 years of age had even stronger associations; RRs in women on estradiol only, the cyclically combined and the continuously combined regimens were 32.2 (95% CI, 3.9 to 267.5), 21.9 (95% CI, 1.9 to 251.5), and 176.9 (95% CI, 22.8 to 1,372.7), respectively. CONCLUSION: HRT with estradiol-progestin regimens, especially continuously combined, may increase the mammographic density in a substantial proportion of women.

Estradiol