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I Persson

Publications and source records attributed to I Persson.

At least 91 records · Page 5Linked to original sources
PubMed1996

S-mephenytoin hydroxylation phenotype and CYP2C19 genotype among Ethiopians.

The polymorphic metabolism of S-mephenytoin and the distribution of two known deleterious mutant CYP2C19 alleles was determined among 114 healthy unrelated black Ethiopians. Six subjects (5.2%) were poor metabolizers (PMs) of S-mephenytoin. The frequencies of the defective CYP2C19*2 (CYP2C19m1) and CYP2C19*3 (CYP2C19m2) alleles were 0.14 and 0.02, respectively. Three of the PMs were homozygous for the CYP2C19*2 allele and the remaining three PMs were heterozygous for both the CYP2C19*2 and CYP2C19*3 mutant alleles. It is concluded that the frequency of PMs for S-mephenytoin is similar in Ethiopians, Zimbabweans and Caucasians and that the CYP2C19*3 allele, for the first time identified in a black population, together with the CYP2C19*2 allele account for all of the defective CYP2C19 alleles among the Ethiopian PMs.

Alleles↗
PubMed1996

Hormone replacement therapy and breast cancer. A review of current knowledge.

More than 50 studies looking at the relationship between hormone replacement therapy and breast cancer have been published. Overall the results are reassuring. There is no evidence of an increased risk of breast cancer after ever use of exogenous estrogens. However, when long term use (i.e. use for more than 10 to 15 years) is considered the majority of data are compatible with a small increase in the risk, in the magnitude of 30 to 50%, possibly limited to women who are currently receiving hormone replacement therapy or who have recently stopped such therapy. This would translate into an increase in the absolute risk of developing breast cancer of 3 to 4% of among postmenopausal women in the Western world. No consistent evidence exists on differing risks of breast cancer with different types of estrogens, and no clear dose-relationship has been found. Risk estimates for combined estrogen-progestogen regimens have been of the same magnitude as for estrogens alone; thus, no clear evidence of a protective effect of the addition of a progestogen has been found. Investigations into a possible interaction between estrogen supplementation and other known risk factors for breast cancer have not yielded any consistent results. Cancers that develop during estrogen therapy have been found to be associated with a favourable prognosis. This could be explained in part by better medical surveillance, and early detection, but may also represent an effect of the treatment itself. Despite the increased incidence of breast cancer after long term hormone replacement therapy, no increased mortality from breast cancer among estrogen users has been found. Thus, on the whole, data seem reassuring. The small increase in the risk of breast cancer after long term hormone replacement therapy use, with no concomitant increase in mortality, is likely to be outweighed by the positive effects of estrogens on the symptoms of the menopause and osteoporosis, and the protective effects of such therapy against cardiovascular disease.

Breast Neoplasms↗
PubMed1996

Frequent distribution of ultrarapid metabolizers of debrisoquine in an ethiopian population carrying duplicated and multiduplicated functional CYP2D6 alleles.

The debrisoquine hydroxylase (CYP2D6) catalyzes the oxidative metabolism of more than 40 different clinically important drugs. The CYP2D6 gene is highly polymorphic. Defect alleles, causing the poor metabolizer phenotype, and also alleles with duplicated or multiduplicated active genes, causing ultrarapid metabolism, have been described. In the current investigation, we have evaluated the CYP2D6 phenotype (n = 115) and genotype (n = 122) among healthy Ethiopians. Only two subjects (1.8%) exhibited metabolic reaction (MR) for debrisoquine > 12.6 and were classified as poor metabolizers. A mutation in exon 1 causing a 34Pro --> Ser amino acid exchange, typical of the Chinese CYP2D6*10B (Ch1) allele and yielding an unstable enzyme, was present among 16% of the population and the carriers exhibited a high MR (0.9-5.0). Increased MR was also found among 18% of the subjects with a 107Thr --> Ile mutation associated to the CYP2D6*17(Z) allele causing diminished activity of CYP2D6 in vivo. Interestingly, 29% of the population investigated carried alleles with duplicated or multiduplicated CYP2D6 genes, indicative of ultrarapid metabolism. Xbal and EcoRI RFLP analyses identified individuals having new alleles with four or five CYP2D6*2(L) genes. Subjects with duplicated or multiduplicated CYP2D6*2 genes exhibited the lowest MR. These results suggest that the Ethiopian population, in comparison to Caucasian, Oriental and other Black populations, is genetically different with respect to the constitution of the CYP2D locus. The results also show that subjects carrying duplicated or multiduplicated active CYP2D6 genes are very common in certain ethnic groups, implicating this issue of potential global importance.

Alleles↗
PubMed1996

Reproductive history and cigarette smoking as risk factors for thyroid cancer in women: a population-based case-control study.

A population-based case-control study was conducted in Northern Norway and Central Sweden to investigate hormonal and reproductive factors and cigarette smoking as determinants of papillary and follicular thyroid carcinoma in women. Information on 191 histologically confirmed cases and 341 age-matched controls was included. No clear association was found with regard to the number of live births, number of pregnancies, a history of incomplete pregnancies, or the use of oral contraceptives or hormonal replacement therapy. However, an early first childbirth (before 20 years of age, or less than 5 years after menarche) was associated with an increased risk of thyroid cancer. There was an increased risk of thyroid cancer among women with a history of artificial menopause compared to those with a spontaneous menopause [odds ratio (OR), 2.52; 95% confidence interval (CI), 0.96-6.62], which was more pronounced for the papillary carcinoma and after adjustment for age at menopause and use of replacement therapy. Cigarette smokers had a decreased risk of borderline statistical significance compared to nonsmokers (OR, 0.69; 95% CI, 0.47-1.01), particularly among premenopausal women (OR, 0.60; 95% CI, 0.38-0.96). This negative association persisted after adjustment for parity, hormonal treatments, and education. Women who started smoking before the age of 15 experienced a marked reduction in risk (OR, 0.38%; 95% CI, 0.18-0.80¿). Moreover, there was a suggestion of a dose-response effect with the amount of cigarettes smoked daily and with duration of the habit. Both the increased risk of artificial menopause and the negative association with smoking are compatible with a relation between levels of estrogens and thyroid cancer among women.

Adenocarcinoma, Follicular↗
PubMed1995

Delayed density-dependence in a small-rodent population.

The role of delayed density-dependent processes in the dynamics of animal populations poses a problem for ecologists; although generally assumed important in populations that show cyclic or chaotic fluctuations, little experimental evidence for such processes exist. Through manipulation of vole densities within enclosed areas it was shown that reproduction, recruitment, and body growth rate in introduced populations were negatively affected by high previous density. In addition, female movement patterns shifted, and territoriality as well as home-range size was increased after high density. The observed changes in female spacing-behaviour suggested that negative effects of previous density were partly mediated by social interactions, and agreed with the finding that smaller (less competitive) females were the ones suffering most from increased competition. Contrary to expectations from recent work, predation could be excluded as the cause of delayed density-dependence in this study. Instead, chemical analyses of a dominating food plant suggested that herbivory at high vole-density had delayed negative effects on food quality.

Animals↗
PubMed1995

The aetiology and pathogenesis of human breast cancer.

Whilst investigators have clearly shown that non-hereditary factors dominate the aetiology of human breast cancer, they have failed to identify quantitatively important causes, and prospects for prevention remain indeed limited. However, progress in epidemiological and basic research has taken place during the last few years. Current evidence suggests that breast cancer may be affected by the intra-uterine environment, that exposures during adolescence are particularly important, and that pregnancy has a dual effect on breast cancer risk: an early increase followed by long-term protection. Great variation exists in the structural development of the breast ductal system already in the newborn--and by inference in utero--and a pregnancy induces permanent structural changes in the mammary gland. We suggest that these observations fit into an aetiological model with the following key components: (1) breast cancer risk depends on the number of cells at risk, the susceptibility of individual cells to malignant transformation, and on the degree of cellular proliferation, notably cells which can act as founders of breast cancer; (2) the number of target cells is determined by the hormonal environment mainly early in life, perhaps already in utero; (3) in adult life, hormones which are non-genotoxic, increase breast cancer risk by increasing selective cell proliferation and thus number of target cells and the risk of retention of spontaneous somatic mutations; (4) while a pregnancy stimulates the growth of already malignant cells or cells close to malignant transformation (and thereby entails a short-term risk increase) the dominating long-term protection occurs due to permanent structural changes, terminal differentiation and perhaps decreased cell proliferation and carcinogen-binding in combination.

Adult↗
PubMed1995

Intrauterine administration of levonorgestrel in two low doses in HRT. A randomized clinical trial during one year: effects on lipid and lipoprotein metabolism.

OBJECTIVE: To investigate the effects on lipid and lipoprotein metabolism of two doses (5- or 10 micrograms/24 h) of levonorgestrel released from an intrauterine device (IUD) in combination with orally administered estradiol (2 mg estradiol valerate) in perimenopausal women. DESIGN: A 1-year prospective randomized single blind clinical trial. SETTING: Department of Obstetrics and Gynaecology, Ostra Hospital, Göteborg, Sweden. SUBJECTS: Fifty-one perimenopausal women with climacteric symptoms. OUTCOME MEASURES: Cholesterol in serum and in lipoprotein fractions; high-density lipoprotein (HDL), low-density lipoprotein (LDL). Triglycerides in serum and in very low-density lipoprotein. RESULTS: In both treatment groups significant elevations in HDL-cholesterol of similar magnitude were observed after 1 month and these changes were maintained during the 12 month observation period. In both treatment groups an initial significant decrease of LDL-cholesterol was observed and the decrement was maintained after 12 months. Serum levels of cholesterol decreased significantly in both groups after 1 month and were maintained after 12 months in the levonorgestrel-IUD (LNG-IUD) 5 micrograms group. However, the initial reduction of serum cholesterol in the LNG-IUD 10 micrograms group did not differ from baseline after 12 months. Serum triglyceride levels fluctuated during the observation period. No significant changes occurred. CONCLUSION: Continuous combined HRT with intrauterine administration of levonorgestrel, 5- or 10 micrograms/24 h, in perimenopausal women was observed to increase HDL-cholesterol and to decrease LDL-cholesterol compared with pretreatment values. The low doses of levonorgestrel did not reverse the beneficial effects on lipid metabolism usually seen after estradiol administration.

Administration, Oral↗
PubMed1995

Trends in breast cancer mortality among Swedish women 1953-92: analyses by age, period and birth cohort.

Trends in breast cancer mortality among Swedish women were explored on the basis of all 51,048 deaths in women 30-89 years of age in Sweden during the period 1953-92. The age-standardised mortality rates were virtually unchanged during the observation period (with a mean of 32 deaths per 100,000 females and year), as were age-specific rates. In age-period-cohort analyses, age alone explained almost all of the variation in the rates. The effects of period and cohort were statistically significant, but very modest. Cohort effects seemed to explain more than period effects, and a weak downward trend starting with women born in 1883-92 was noted. A change in 1981 in the policy to classify the causes of death from the death certificates seemed to entail an artificial lowering of the mortality rates in women older than 75 years. It is concluded that breast cancer mortality in Sweden during the last 40 years has been remarkably stable, in spite of a substantial and constant increase in the incidence. This divergence between mortality and incidence reflects improved survival, which could in part be explained by earlier detection and more efficient treatment, or by an increasing occurrence of less aggressive tumours.

Adult↗
PubMed1995

Genetic polymorphism of cytochromes P450 1A1, 2D6 and 2E1: regulation and toxicological significance.

Because of important roles of cytochromes P450 in the metabolic activation of many precarcinogens, extensive research in the past has focused on the relationship between the distribution of polymorphic variants of different isozymes of P450 and cancer susceptibility. In this respect three isozymes in particular have been studied, CYP1A1, CYP2D6, and CYP2E1. Both CYP1A1 and CYP2E1 participate in the metabolism of many suspected as well as established carcinogens, whereas essentially only one carcinogenic substrate has been identified for CYP2D6. Polymorphic sites for the three CYP genes have been identified both in the open reading frame as well as in introns and the regulatory 5' region. In the present contribution we summarize the molecular epidemiological research relating CYP polymorphism to cancer susceptibility and in some cases to toxicity. An interesting polymorphism has been described on the phenotypic level for the inducibility of CYP1A1, a polymorphism that in some studies has been related to a mutation in the 3' flanking region of the CYP1A1 gene. However, the genetic basis for this polymorphism might be inherited in the genes coding for proteins responsible for the induction of CYP1A1, ie, the Ah receptor or the ARNT protein. Data on lung cancer and CYP1A1 gene polymorphism indicate that carriers of genotypes associated with CYP1A1 inducibility are at higher risk for cancer, but that, at least for Caucasians, the recognized mutations probably identify only a fraction of the inducible individuals. The amount of DNA adducts correlates well in some studies to the individual activity registered for CYP1A1. CYP2D6 phenotype and genotype have mainly been related to the incidence of lung cancer, but results from 13 different studies now show an absence of any significant correlation between these parameters. In the case of CYP2E1, some studies indicate a relationship between lung cancer and the occurrence of a rare allele, although future research is needed in order to establish a significant relationship. It is concluded that, at the present stage, none of the polymorphic sites determined in the CYP genes can yet be used as markers for increased lung cancer risk. Future research in this field might be focused on the establishment of new polymorphic sites in the CYP genes, affecting inducibility or function, and on the molecular basis for the interesting differences in CYP1A1 inducibility.

Animals↗
PubMed1995

Cytokine gene expression during infection of mice lacking CD4 and/or CD8 with Trypanosoma cruzi.

The expression of lymphokine genes during infection of virulent (Tulahuén) or mild (CA-I) strains of T. cruzi was studied in mice lacking CD4 and/or CD8 molecules. The increased susceptibility of CD4- and CD4-CD8- mice to infection with CA-I or Tulahuén was parallelled by diminished IFN-gamma mRNA levels. Nitric oxide release and inducible nitric oxide synthase mRNA accumulation by cells from Tulahuén infected CD4- mice was also diminished. CD8- (but not CD4-CD8- mice) showed an increased IL-4 and IL-10 mRNA accumulation upon infection with both strains of T. cruzi. A 'Th2-like' response (higher IL-4 and IL-10 mRNA to IFN-gamma mRNA ratio), was also observed when cells from noninfected CD8- mice were stimulated with T cell mitogens.

Animals↗
PubMed1995

Validity of information on gynecological operations in the Swedish in-patient registry.

In order to validate information held at the Swedish In-patient Registry on oophorectomy and/or hysterectomy procedures, the register codes were compared with data from the medical records in a random sample of 1,338 women. Only 1% of these codes were missing but 5% were erroneous, which in most cases meant that the oophorectomy had been misclassified. The positive predictive value of operation codes was high, ranging from 86 to 100% of the registered events. The actual procedures among women registered with a code for hysterectomy with or without oophorectomy comprised hysterectomy alone in 47% of the women and hysterectomy with a bilateral or unilateral oophorectomy in 30% and 20%, respectively. The reliability of register codes for major gynecological surgical procedures is good, but when the code for hysterectomy is used, medical record data are needed to ascertain the ovarian status. Revised codes are therefore recommended.

Adult↗
PubMed1994

Parity, age at first childbirth, and risk of ovarian cancer.

Increasing parity is associated with a reduction in the risk of ovarian cancer, but it is not clear whether this association applies to different histopathological types and to borderline tumours. Moreover, the temporal relations are poorly understood, and the possible role of age at first birth remains unequivocal. We have investigated these issues in a case-control study nested in a nationwide cohort of women born between 1925 and 1960 in Sweden. During follow-up until 1984, 3486 invasive ovarian cancers (2992 epithelial, 330 stromal, 149 germ-cell, 15 not classifiable) and 510 tumours of borderline malignant potential were diagnosed. 5 individually age-matched controls (total 19,980) were selected for each case woman. After simultaneous adjustment for parity and age at first birth, increasing parity was associated with a pronounced consistent decrease in relative risk of all invasive cancers (odds ratio for each additional birth 0.81 [95% Cl 0.77-0.85]), epithelial cancer (0.81 [0.77-0.86]), stromal cancer (0.84 [0.72-0.98]), and germ-cell cancer (0.71 [0.48-1.05]), but a less consistent decrease for borderline tumours (0.92 [0.81-1.04]). The risk of ovarian cancer decreased by about 10% for each 5-year increment in age at first childbirth (odds ratios 0.89 [0.84-0.94] epithelial cancer, 0.92 [0.77-1.10] stromal cancer, 0.92 [0.65-1.32] germ-cell cancer, 0.93 [0.80-1.09] borderline tumours). Because our findings cannot be readily explained by theories involving incessant ovulation or high serum concentrations of gonadotropins, new aetiological hypotheses are needed. Pregnancy-dependent clearance from the ovaries of cells that have undergone malignant transformation could explain the reproductive risk factors for ovarian cancer.

Adolescent↗