Search PubMed⌕ Search

Biomedical subjects

I Persson

Publications and source records attributed to I Persson.

At least 73 records · Page 4Linked to original sources

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↗

Intrauterine administration of levonorgestrel 5 and 10 microg/24 hours in perimenopausal hormone replacement therapy. A randomized clinical study during one year.

OBJECTIVE: To investigate the clinical effects especially with regard to histopathology and bleeding patterns by levonorgestrel (5- or 10 microg/24 h) released from an intrauterine system (IUS) in combination with estradiol valerate (2 mg) given daily or transdermal estradiol (50 microg/24 h) in perimenopausal women. DESIGN: A prospective randomized single blind comparison during twelve months. SUBJECTS: One hundred and twelve perimenopausal women with vaso-motor symptoms. OUTCOME MEASURES: Histopathological assessment of the endometrium, ultrasonographic measurement of endometrial thickness, bleeding patterns, and acceptability. RESULTS: A total of 108 women started the study and 12 discontinued. The most common reason for discontinuation was frequent bleeding (six women). Thus, 96 (89%) women were followed for twelve months. In both the 5- and 10 microg levonorgestrel IUS groups the endometrium in all women but one was non-proliferative after twelve months and no case of hyperplasia was found. Irregular bleeding was reported during the first months of treatment but decreased after six months. At the end of the study 62% in the 5 microg- and 61% in the 10 microg group were amenorrhoic. The effects on bleeding patterns did not differ between the two levonorgestrel dosages. CONCLUSION: Continuous combined HRT was well accepted in perimenopausal women when the progestogen was given in an IUS. IUS's releasing 5- or 10 microg/24 h levonorgestrel seemed to minimize the progestogenic side effects and proved to be sufficient for effective prevention of endometrial stimulation by estrogen treatment in HRT in perimenopausal women.

Administration, Cutaneous↗

[Diet and antioxidant--a nutritional intervention study].

It has been implicated that high vegetable intake is associated with a decreased risk for various forms of cancer in epidemiological studies. A major defense system against cancer has shown to be antioxidants. Glutathione S-transferases (GSTs), one of the major defense ststems against oxidative damage, can be induced by antioxidant and addition of vegetables to their normal diet. Serum retinol and a-tocopherol were determined by HPLC and the gene expression of GST pi in lymphocytes was measured by reverse transcription-polymerase chain reaction (RT-PCR) techniques. The results showed that there was on significant difference in the levels of serum retinol and a-tocopherol before and after the addition of vegetables. GST pi mRNA levels in lymphocytes were higher in four out of five subjects after addition of vegetables. The results suggested that it might be other antioxidants than vitamin A and E in the vegetables that induced the gene transcription of GST pi.

Adult↗

Cancer incidence and mortality in women receiving estrogen and estrogen-progestin replacement therapy--long-term follow-up of a Swedish cohort.

We analyzed cancer incidence and mortality in a cohort of 22,597 Swedish women who were prescribed replacement hormones. After 13 years of follow-up in national registries, 2,330 incident cancer cases and 848 cancer deaths were observed. Overall, our results were reassuring since incidence rate ratios (SIRs) for 16 cancer sites and mortality ratios (SMRs) for all 10 examined sites were at, or lower than, unity. However, we found that exposure to an estrogen-progestin combined brand was associated with an increasing relative risk of breast cancer with follow-up time, the SIR reaching 1.4 (95% CI 1.1-1.8) after 10 years of follow-up. The relative risk of endometrial cancer was substantially increased, with the highest SIR of 5.0 (95% CI 1.6-5.9) in women prescribed estrogens alone, whereas those given an estrogen-progestin combination showed no elevation in risk. The risk estimates for liver and biliary tract cancers and for colon cancer were reduced by about 40%, notably in women prescribed the estradiol-progestin compound. Further detailed analyses revealed no evidence of adverse or protective effects on the risk of ovarian, uterine cervical, vulvar/vaginal, rectal, pancreatic, renal, lung, thyroid and other endocrine cancers, brain tumors, malignant melanoma or other skin cancers. Hormone replacement therapy was not associated with an increase in mortality for any cancer site, at this time of follow-up. For breast and endometrial cancers, SMRs were below baseline but tended to increase with follow-up time. We conclude that hormone replacement increases the endometrial-cancer risk after unopposed estrogens and the breast-cancer risk-notably after estrogen-progestin combined therapy-and tentatively suggest that it exerts a protective effect against colon and liver cancer risks.

Aged↗

Prognostic characteristics in breast cancers after hormone replacement therapy.

We examined the influence of hormone replacement therapy (HRT) on breast tumour biology by comparing the prognostic characteristics of breast cancers and survival in 121 women prescribed replacement hormones before diagnosis with those in 1468 women without such treatment. The women receiving HRT had a lowered relative risk of being diagnosed with tumours of more than 20 mm in diameter, OR = 0.7 (CI 0.5-1.0) and axillary lymph node dissemination, OR = 0.7 (CI 0.4-1.1). These risk reductions were most pronounced and statistically significant in the women who had been prescribed a combined estradiol-progestin regimen. The patients in this compound group also had a diminished relative risk of having poorly differentiated tumours. Further, there was an indication that the women prescribed HRT, and especially those with conjugated estrogens/estradiols alone, had a decreased relative risk of developing aneuploid tumours. There was no clear pattern for women receiving the biologically weak oestriol, although risk estimates were generally higher for unfavourable tumours in comparison with those receiving the higher potency compounds. Adjustments for indications of earlier detection (i.e. lead time bias) did not influence the pattern or magnitude of the risk estimates. No association between any type of HRT and survival after breast cancer diagnosis was noted, but analyses were based only on 19 breast cancer deaths among exposed patients. We conclude that breast cancers occurring after treatment with HRT, especially the combined estrogen-progestin regimen, seem to have more favourable tumour features than tumours in non-treated women. Our findings may reflect a less aggressive biological behaviour of breast cancers in women receiving HRT, or in part be explained by the earlier detection of the tumours in these women.

Aged↗

Cancer risk in women receiving estrogen-progestin replacement therapy.

OBJECTIVES AND METHODS: The epidemiological literature was reviewed in order to evaluate the relationship between hormone replacement therapy and risk of cancer in the breast and reproductive organs. RESULTS: For breast cancer, there is no evidence of an overall increase in the risk. According to several studies, but not all, the duration of intake seems to affect the risk. Many years of intake of both estradiol compounds and conjugated estrogens can be assumed to increase the risk of breast cancer 1.5-2-fold. The addition of progestins does not seem to alter (reduce) the duration-risk relationship. The magnitude of risk increase is likely to be small and may be explained partly by methodological problems, or by differences in study populations. The prognosis in patients with HRT-related breast cancer seems to be more favourable than for non-exposed breast cancer patients. Because of the importance of the issue, and inconsistencies in results, further research is urgent. Especially, there is an urgent need to define sub-groups of women who would be susceptible to an adverse influence of HRT. Regarding endometrial cancer, a duration-dependent strong risk relationship with long-term intake of estrogens only is established. The level of risk increase is about 10-fold after 10 or more years of intake, a risk relationship that seems to decrease after discontinuation of treatment. Added progestins for at least 10 days per cycle can reduce or eliminate the risk increase. Tumors occurring after estrogen replacement have favourable biological characteristics. Future research will be needed to define the long-term safety of various progestin regimens. Ovarian cancer risk does not seem to be affected by HRT. Available data are inconsistent and contradictory. Due to the pronounced protective effect of oral contraceptives, further research is needed to measure effects of estrogen-progestin combined regimens. Cervical cancer risk has not been shown to be affected by HRT. CONCLUSIONS: It is concluded that hormone replacement therapy, with estrogens alone or estrogens combined with progestins, may have important effects on the risk of cancer, particularly in the breast and endometrium. Therefore, when making a risk-benefit assessment of long-term HRT, possible risk relationships should be considered.

Breast Neoplasms↗

A novel mutant variant of the CYP2D6 gene (CYP2D6*17) common in a black African population: association with diminished debrisoquine hydroxylase activity.

1. The debrisoquine hydroxylase (CYP2D6) is polymorphically distributed. Not only are there differences in the proportions of extensive metabolisers to poor metabolisers in various ethnic groups, but there are also pronounced variations in the metabolic capacity among those classified as extensive metabolisers. 2. The mean debrisoquine metabolic ratio of Caucasian extensive metabolisers is lower than that for a number of African populations. In the present study, we have searched for novel CYP2D6 mutations to explain the diminished enzyme activity in African populations. 3. Three Zimbabwean Shona subjects with EM phenotypes (metabolic ratios for debrisoquine of 0.4, 1.5 and 10.5 respectively) were selected and the open reading frame of the CYP2D6 gene of each was sequenced. 4. The subject with metabolic ratio of 10.5 was found to be homozygous for an allele with a nucleotide exchange in exon 2, 1111C-->T causing a 107Thr-->Ile amino acid exchange in a conserved region of the enzyme. In addition, he was homozygous for the 2938C-->T and 4268G-->C mutations causing 296Arg-->Ser and 486Ser-->Thr amino acid substitution found in the CYP2D6*2 allele. 5. Seventy-six Zimbabwean Shona subjects were subsequently genotyped for the 1111C-->T mutation and for the intron 1 gene conversion present in the CYP2D6*2 gene. The 1111C-->T mutation was found at an allele frequency of 34% and was only present in alleles carrying the gene conversion in intron 1 indicative for the CYP2D6*2 gene. 6. This allele (CYP2D6*17), containing the 1111C-->T, 2938C-->T and 4268G-->C mutations, was found to be strongly associated with lower capacity for debrisoquine hydroxylation. We therefore postulate that the CYP2D6*17 allele might contribute to the molecular basis of the previously established diminished debrisoquine hydroxylase activity in African Bantu populations.

Black People↗

Long-term trends in incidence of and mortality from acute myocardial infarction and stroke in women: Analyses of total first events and of deaths in the Uppsala Health Care Region, Sweden.

We studied the trends from 1969 to the mid-1980s in the incidence and mortality of acute myocardial infarction and stroke in Swedish women residing in the Uppsala Health Care Region. We used data from the Inpatient Care and Causes of Death registers to obtain total first event incidence and mortality rates. In our population, there were 20,182 acute myocardial infarctions and 30,462 stroke events, and 17,359 and 21,336 deaths, respectively. We found an average overall annual increase of 1.3% in the age-standardized incidence of acute myocardial infarction during the 1970s, followed by decreasing rates during the early 1980s. Mortality was virtually unchanged. Notably, among women 45-49 years of age, we observed a rising trend during the whole period, whereas in the oldest age groups, the increase slowed and reversed in the latter years. Both the incidence and mortality for stroke declined steadily: the age-standardized incidence fell by an average of 2.1% per year for all stroke and 7.8% for intracerebral hemorrhage. The falling rate of stroke was best explained by birth cohort effects, with a 30% reduction in women born in 1920 and later as compared with those born in 1890. We conclude that important changes in Swedish women's cardiovascular health have taken place and that increasing cigarette smoking and hypertensive treatment are major determinants.

Adult↗