More about: effect of hormone replacement therapy on breast cancer risk: estrogen versus estrogen plus progestin.
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Breast Neoplasms↗
Biomedical subjects
I Persson
Publications and source records attributed to I Persson.
Risk of myocardial infarction after oophorectomy and hysterectomy.
To determine the risk of developing a first myocardial infarction after a hysterectomy and/or oophorectomy. Case-cohort analysis performed among 17,126 women in the Uppsala Health Care Region of Sweden, who had undergone a hysterectomy and/or oophorectomy in 1965 to 1983. Record linkage was used for follow-up and medical records to ascertain the actual history of oophorectomy. Risk estimates were calculated by relating the observed number of cases in the cohort to that expected on the basis of incidence rates in the population. Overall, 214 cases of myocardial infarction were observed. In premenopausal women a bilateral oophorectomy alone tended to increase the relative risk 1.6; 95% CI 0.8-3.1, but this operation combined with hysterectomy increased the risk only among those aged 50 and over at surgery. Hysterectomy at premenopausal age or unilateral oophorectomy did not alter the risk of myocardial infarction. In naturally menopausal women, hysterectomy-mainly for uterine myoma-was associated with a four-fold increase in relative risk (3.8; 95% CI 1.9-7.8). Hysterectomy for treatment of myoma performed after a natural menopause is linked to an excess risk for myocardial infarction. Bilateral oophorectomy before menopause may increase the risk of myocardial infarction.
Adult↗
Breast cancer risk and lifetime leisure-time and occupational physical activity (Sweden).
OBJECTIVE: To clarify whether type and timing of physical activity affect postmenopausal breast cancer risk. METHODS: In a population-based case-control study within the Swedish female population 50-74 years of age, 3347 women with invasive, postmenopausal breast cancer (84% of all eligible) and 3455 controls (82% of all selected) reported on past leisure-time physical activity. Record linkage to decennial census data (1960-1990) provided estimates of their occupational physical activity. Odds ratios with 95% confidence intervals were estimated by multivariate logistic regression. RESULTS: After adjustment for potential confounders, women in sedentary occupations during their reproductive years (25-44 years of age) had a 50% higher risk for postmenopausal breast cancer, compared to those with the physically most demanding jobs. Only the most recent leisure-time physical activity was associated with a significant risk reduction. Women with the combination of sedentary jobs and lack of leisure-time exercise had a three-fold higher risk of breast cancer, compared to the physically most active both inside and outside the workplace. CONCLUSION: Effects of occupational and leisure-time physical activity on breast cancer risk appear to have different latency times, and/or to be effect-modified by age or reproductive status. Although chance might explain our findings, it is advisable to consider type and timing of physical activity in future studies.
Adult↗
Physical activity and postmenopausal endometrial cancer risk (Sweden).
OBJECTIVES: To examine the hypothesis that sedentary women have an increased risk of endometrial cancer compared to physically active women. METHODS: This is a population-based case-control study in the entire Swedish female population aged 50-74 years in 1994-1995. We obtained self-reported information on leisure-time physical activity during childhood, at ages 18-30, and recently from 709 incident case women with endometrial cancer and 3368 population controls. Occupational physical activity was estimated through record linkage to the Swedish census data from 1960, 1970, 1980, and 1990. Odds ratios (OR) and 95% confidence intervals (CI) were calculated for different activity levels by multivariate logistic regression, taking into account potential confounders. RESULTS: Comparing lowest to highest (reference) levels of physical exercise, we observed statistically significant associations with risk of endometrial cancer for leisure-time activity at age 18-30 years (multivariate OR = 1.4; 95% CI = 1.0-1.8; p for trend 0.01) and in recent years (multivariate OR = 1.3; 95% CI = 1.0-1.7; p for trend 0.01). We found similar associations comparing lowest to highest (reference) levels of occupational activity assessed at the censuses in 1980 (multivariate OR = 1.4; 95% CI = 1.0-1.9; p for trend 0.03) and 1990 (multivariate OR = 1.3; 95% CI = 0.9-1.9, p for trend 0.05), but a less consistent association with censuses in 1960 and 1970. The increased risk associated with low level of occupational physical activity was confined to women who were not obese and to women who were smokers. CONCLUSION: Our data, in conjunction with past epidemiological studies, indicate that both occupational and leisure-time physical activity may reduce the risk for postmenopausal endometrial cancer.
Aged↗
Body size in different periods of life, diabetes mellitus, hypertension, and risk of postmenopausal endometrial cancer (Sweden).
OBJECTIVE: To measure the association between endometrial cancer risk and obesity at age 18 and recently, adult weight gain, diabetes mellitus and hypertension. METHODS: We performed a population-based, nationwide case-control study among postmenopausal women aged 50-74 years in Sweden, including 709 incident cases with histopathologically verified endometrial cancer and 3368 controls. RESULTS: Compared to lean women (recent body mass index (BMI), i.e. kg/m2 below 22.5), overweight women (recent BMI 28-29.99) had a 50% increase in risk for endometrial cancer (OR 1.5, 95% CI 1.0-2.1). Obese women (recent BMI 30-33.99) had a 3-fold increased risk (OR 2.9, 95% CI 2.0-4.0), and markedly obese women (recent BMI > or = 34) a 6-fold increased risk (OR 6.3, 95% CI 4.2-9.5). The OR for Type 2 diabetes mellitus was 1.5 (95% CI 1.0-2.1) and for Type 1 diabetes mellitus it was 13.3 (3.1-56.4). The effect of recent BMI was similar for tumors having different degrees of differentiation and myometrial invasion, and did not vary with age, time since menopause, smoking status, diabetes mellitus, and use of contraceptives. Hypertension increased risk only among obese women. BMI at age 18, height, and adult weight change were not independent risk factors. CONCLUSIONS: Recent overweight/obesity and diabetes mellitus (Types 1 and 2) are associated with endometrial cancer risk. Hypertension increases risk among obese women.
Adolescent↗
Influence of vegetables on the expression of GSTP1 in humans--a pilot intervention study (Sweden).
BACKGROUND: There are indications that a diet rich in vegetables and/or fruit has a protective effect against several types of diseases, including cancer. Data from experimental and epidemiological studies suggest that antioxidant constituents may provide protection against environmental carcinogens. AIMS: This study investigated the effect of additional vegetables in the diet on the expression of the endogenous antioxidant enzyme GSTP1 in human lymphocytes. METHODS: Six subjects were given an addition of mixed vegetables to their normal diet for a period of three weeks. The expression of GSTP1 protein and mRNA in lymphocytes was measured by Western blot and RT competitive PCR. RESULTS: After the intervention all six subjects had lower levels of GSTP1 mRNA, and five of the six subjects had lower GSTP1 protein levels. This suggests that increased vegetable intake decreases GSTP1 expression, possibly through the supply of additional antioxidants.
Adult↗
Estrogen receptor alpha gene polymorphisms and endometrial cancer risk.
Since the estrogen receptor alpha (ER) is an important mediator of hormonal responses such as proliferation in estrogen-sensitive tissues, we hypothesized that polymorphisms in the ER gene could be functional and associated with endometrial cancer risk. We performed a population-based case-control study in Sweden, focusing on restriction fragment length polymorphisms for XbaI and PvuII and an upstream TA repeat polymorphism. In the main analysis, 154 cases and 205 controls who never used hormone replacement therapy took part and we calculated age-adjusted and multivariate odds ratios (OR) and 95% confidence intervals (CI) using unconditional logistic regression. The XbaI X allele appeared to confer a reduced risk for endometrial cancer. The multivariate OR for the XX genotype was 0.52 (95% CI 0.21-1.29) compared to the xx genotype and there were suggestions of decreasing risk with increasing number of X alleles (P for trend = 0.07). The PvuII PP genotype was also associated with a non-significantly decreased risk for endometrial cancer (multivariate OR 0.70, 95% CI 0.34-1.44) compared with the pp genotype (P for trend = 0.43). The multivariate OR for two short TA (<19 repeats) alleles versus two long alleles was 1.54 (95% CI 0. 73-3.27) and there were suggestions of increasing risk with increasing number of short alleles (P for trend = 0.26). We observed the same pattern of results in an expanded group of subjects, which included women who had used hormone replacement (in total 288 cases and 392 controls). Our data suggest that variants of the ER gene may be associated with an altered risk of endometrial cancer.
Aged↗
New leads on ovarian carcinogenesis.
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Contraceptives, Oral, Combined↗
Breast cancer following breast reduction surgery in Sweden.
Women undergoing breast reduction surgery have been reported to be at low subsequent risk of breast cancer, especially when the surgery is performed after age 40. To evaluate the age and time-related patterns of cancer risk following surgical removal of breast tissue, we identified 31,910 women who underwent breast reduction surgery from 1965 to 1993 in Sweden using hospital discharge register data. There were 19,975 women (63 percent) under age 40 at surgery. Linkages with Swedish registries for cancer, death, and emigration were based on unique national registration numbers assigned to each Swedish resident. Cancer incidence was contrasted with that expected in the general population based on age- and calendar year-specific data from the nationwide cancer registry. Overall, 161 incident breast cancers were identified during 238,765 person-years of observation (mean, 7.5 years) compared with 223.9 expected (standardized incidence ratio = 0.72; 95 percent confidence interval = 0.61 to 0.84). The reduction in risk of breast cancer was most pronounced for women whose operations were performed after age 50 (SIR = 0.57) and for those followed for more than 5 years (SIR = 0.68). Among women operated on before age 40, risk was nonsignificantly elevated within the first 5 years after surgery (SIR = 1.47; 95 percent CI = 0.89 to 2.30) but tended to be reduced thereafter (SIR = 0.80; 95 percent CI = 0.55 to 1.13). The magnitude of the reduction in risk thus appears directly related to age at surgery. Women followed for an average of 7.5 years after bilateral breast reduction surgery, were at a statistically significant 28 percent decreased risk of breast cancer. The current study is thus consistent with a protective effect following partial removal of breast glandular tissue.
Adolescent↗
Organochlorines and endometrial cancer risk.
There is concern that persistent environmental pollutants such as dichlorodiphenyltrichloroethane (DDT) and polychlorinated biphenyls (PCBs) increase breast cancer risk, at least partially through estrogenic effects. Because the endometrium is more sensitive to estrogenic stimulation than the breast, such a carcinogenic effect should be more pronounced in the endometrium than the breast. In a population-based case-control study in Sweden, we measured serum concentrations of 10 chlorinated pesticides and 10 PCB congeners in 154 endometrial cancer cases and 205 population controls. Information on potential confounders was obtained by mailed questionnaires. We used logistic regression to calculate odds ratios (ORs) as measures of relative risk. We performed analyses for lipid-adjusted concentrations of each individual substance and after grouping substances according to putative hormonal effects. We found no significant associations of increasing levels of pesticide or PCB exposure with endometrial cancer risk. The multivariate OR was 1.0 (95% confidence interval, 0.6-2.0; P for trend, 0.78) for the highest compared with the lowest quartile of dichlorodiphenyldichloroethylene (DDE), the predominant dichlorodiphenyltrichloroethane metabolite. Corresponding ORs were 1.0 for hexachlorobenzene, 0.9 for beta-hexachlorocyclohexane, 1.4 for oxychlordane, and 1.2 for trans-nonachlor. Analyses of substances grouped by putative hormonal effect also showed no associations with endometrial cancer risk. For all estrogenic compounds, the OR for the highest compared with the lowest quartile was 1.1 (95% confidence interval, 0.6-2.2; P for trend, 0.90). Our data do not support the hypothesis that the organochlorine exposure studied increases the risk for endometrial cancer.
Aged↗
Influence of perinatal factors on the onset of puberty in boys and girls: implications for interpretation of link with risk of long term diseases.
The authors examined the hypothesis that perinatal factors influence the onset of puberty. Children born as singletons in Uppsala, Sweden, in 1973-1977 were followed for height development before and during their school years (through 16 years of age). In all, 62 children born after preeclampsia, 129 born prematurely, 90 born small for gestational age, 175 born large for gestational age, 49 born short for gestational age, and 38 born tall for gestational age were compared with 688 "normal" children. Differences in age and height at puberty onset and age at menarche were analyzed using the t test and analyses of covariance. For boys, the mean age at puberty onset did not differ between normal boys and those with perinatal factors. Boys born small or short for gestational age were 4 cm shorter than normal boys, and those born large for gestational age were 3 cm taller than normal boys. Among girls, patterns for differences in height were similar. Girls born small for gestational age were 5 months younger than normal girls at the onset of puberty and menarche. Patterns of early childhood growth seemed to explain the relations between these perinatal factors and height and age at puberty. The authors conclude that body size at birth affects stature at puberty; in girls, smallness for gestational age is associated with earlier puberty. Associations between intrauterine exposures and disease risk may be confounded by, or mediated through, effects on adolescence.
Adolescent↗
Risk of endometrial cancer following estrogen replacement with and without progestins.
BACKGROUND: Unopposed estrogen replacement therapy (i.e., estrogen without progestins) increases the risk of endometrial cancer. In this study, we examined the endometrial cancer risk associated with combined estrogen-progestin regimens currently in use, since the safety profiles of these regimens have not been clearly defined. METHODS: We conducted a nationwide population-based, case-control study in Sweden of postmenopausal women aged 50-74 years. We collected information on use of hormone replacement from 709 case patients with incident endometrial cancer and from 3368 control subjects. We used unconditional logistic regression to calculate odds ratios (ORs) as estimates of relative risks. All individual comparisons were made with women who never used the respective hormone replacement regimens. RESULTS: Treatment with estrogens alone was associated with a marked duration- and dose-dependent increase in the relative risk of endometrial cancer. Five or more years of treatment had an OR of 6.2 for estradiol (95% confidence interval [CI] = 3.1-12.6) and of 6.6 for conjugated estrogens (95% CI = 3.6-12.0). Following combined estrogen-progestin use, the association was considerably weaker than that for estrogen alone; the OR was 1.6 (95% CI = 1.1-2.4) after 5 or more years of use. This increase in risk was confined to women with cyclic use of progestins, i.e., fewer than 16 days per cycle (most commonly 10 days per cycle [OR = 2.9; 95% CI = 1.8-4.6 for 5 or more years of use]), whereas continuous progestin use along with estrogens was associated with a reduced risk (OR = 0.2; 95% CI = 0.1-0.8 for 5 or more years of use). CONCLUSION: The risk of developing endometrial cancer is increased after long-term use of estrogens without progestins and with cyclically added progestins. Continuously added progestins may be needed to minimize the endometrial cancer risk associated with estrogen replacement therapy.
Adenocarcinoma↗
Low-potency oestrogen and risk of endometrial cancer: a case-control study.
BACKGROUND: Urogenital symptoms are common among postmenopausal women. Such symptoms may be alleviated by low-potency oestrogen formulations administered orally or vaginally. Although low-potency oestrogen formulations are assumed to have few, if any, adverse effects on the endometrium, risk of endometrial neoplasia has not been quantified. METHODS: In a nationwide population-based case-control study in Sweden of endometrial cancer among postmenopausal women, we obtained detailed information on hormone replacement from 789 cases of endometrial cancer and 3368 population controls. In a histopathological review, 80 cases were reclassified as having endometrial atypical hyperplasia. Odds ratios and 95% CI were calculated with unconditional logistic regression. FINDINGS: After multivariate adjustment, oral use of oestriol 1-2 mg daily increased the relative risk of endometrial cancer and endometrial atypical hyperplasia: the odds ratios for at least 5 years of use compared with never use were 3.0 (95% CI 2.0-4.4) and 8.3 (4.0-17.4), respectively. The association was stronger for well-differentiated cancers and those with limited invasion. The excess relative risk was lost rapidly after cessation of treatment. Only weak associations were observed between vaginal application of low-potency oestrogen formulations and relative risk of endometrial neoplasia. INTERPRETATION: Oral, but not vaginal, treatment with low-potency oestrogen formulations increases the relative risk of endometrial neoplasia. Thus close surveillance of patients is needed, and addition of a progestagen should be considered.
Administration, Intravaginal↗
Genetic polymorphism of xenobiotic metabolizing enzymes among Chinese lung cancer patients.
Polymorphisms in xenobiotic metabolizing enzymes have been implicated in inter-individual and inter-ethnic differences in cancer susceptibilty. Several studies have indicated an association between variant alleles of the human CYP1A1, CYP2E1 and GSTM1 genes and lung cancer. Activity of microsomal epoxide hydrolase (HYL1) has also been associated with lung cancer, and 2 variant alleles causing amino acid substitutions have been described. We have investigated genetic polymorphisms of the CYP1A1, CYP2E1, GSTM1 and HYL1 genes in 76 Chinese lung cancer patients and 122 healthy Chinese subjects. The allele frequency of the CYP1A1*2B allele was 0.21 among lung cancer patients and 0.20 in the reference group, whereas the corresponding values for the CYP1A1*2A allele were 0.34 and 0.36. The CYP2E1*5B and CYP2E1*6 alleles were less frequent among the cancer patients (0.20 and 0.22) compared with healthy subjects (0.25 and 0.26). The frequency distribution of the HYL1*2 allele was 0.49 among lung cancer patients and 0.42 in the reference group, and the corresponding frequencies for the HYL1*3 allele were 0.13 and 0.10. The homozygous GSTM1*0 genotype was found in 64% of lung cancer patients and in 66% of healthy subjects. Among heavy smokers, the frequency was 73%. The differences in the distribution of variant CYP1A1, CYP2E1 and GSTM1 alleles in lung cancer patients and healthy controls were not statistically significant. Our results indicate that the polymorphisms investigated are of minor importance as genetic susceptibility markers for lung cancer in this population. An increased risk for lung cancer in subjects carrying the HYL*3 allele was observed and suggests that polymorphism in this gene might possibly be a susceptibility factor in the Chinese population.
Adult↗
Breast-cancer risk following long-term oestrogen- and oestrogen-progestin-replacement therapy.
While use of hormone-replacement therapy (HRT) effectively alleviates menopausal symptoms and prevents osteoporosis and possibly cardiovascular disease, there is concern of a detrimental impact on breast-cancer risk. There is a particular lack of data regarding the effect of long-term use of oestrogen-progestin combinations on breast-cancer risk. We conducted a large epidemiological study in Sweden, where combined oestrogen-progestin treatment has been predominant, to examine the influence of different regimens of menopausal hormone therapy on breast-cancer risk. In this population-based case-control study, 3,345 women aged 50 to 74 years with invasive breast cancer (84% of all eligible) and 3,454 controls of similar age (82% of all selected) were included. Mailed questionnaires and telephone interviews were used to collect detailed information on use of hormone replacement and on potential confounding factors. Odds ratios (OR) and 95% confidence intervals (CI) were estimated through multiple logistic regression. There was a trend of increasing breast-cancer risk with duration of oestrogen/oestrogen-progestin use (OR for women treated at least 10 years, 2.43; 95% CI, 1.79-3.30, as compared to never-users), with statistically significant estimates only for women with BMI<27 kg/m2. Excess risks were observed to current use and use that ceased more than 10 years ago (OR for women treated at least 5 years, OR was 2.68, 95% CI, 2.09-3.42, and OR 2.57, 95% CI, 1.28-5.15, as compared with never-users, respectively). A positive association which was noted for use of oestrogen combined with testosterone-derived progestins appeared especially pronounced with continuously combined regimens. Long-term use of replacement oestrogens with or without progestins may substantially increase the incidence of post-menopausal breast cancer, particularly among non-obese women.
Breast Neoplasms↗
Oral-contraceptive use and risk of hip fracture: a case-control study.
BACKGROUND: Epidemiological studies indicate a protective effect of postmenopausal oestrogen therapy on the risk of osteoporotic fractures. Whether premenopausal oestrogen exposure in the form of oral contraceptives also reduces the risk of osteoporotic fractures remains uncertain. METHOD: We did a population-based case control study of hip fracture among Swedish postmenopausal women, 50-81 years of age, through mailed questionnaires and telephone interviews. Of those women who were eligible, 1327 (82.5%) cases and 3312 (81.6%) randomly selected controls responded. FINDINGS: 130 (11.6%) cases and 562 (19.1%) controls reported ever-use of oral contraceptives. Ever-use of oral contraceptives was associated with a 25% reduction in hip fracture risk (odds ratio 0.75 [95% CI 0.59-0.96]). Women who had ever used a high-dose pill (equivalent to > or = 50 microg ethinylestradiol per tablet) had a 44% lower risk for hip fracture than never-users (0.56 [0.42-0.75]). No overall trend was observed with duration of oral-contraceptive use, or time since last use. However, when making comparisons with women who have never used oral contraceptives, the odds ratios for hip-fracture were 0.69 (0.51-0.94) for use after age 40, 0.82 (0.57-1.16) for use at ages 30-39, and 1.26 (0.76-2.09) for use before age 30. INTERPRETATION: Our results imply that in postmenopausal women, oral-contraceptive use late in reproductive life may reduce the risk of hip fracture, although we recognise the limitations of the case-control method.
Adult↗
Performance in functional balance tests during menopausal hormone replacement: a double-blind placebo-controlled study.
BACKGROUND AND PURPOSE: Recent studies have indicated that oestrogens might have an effect on postural control. The purpose of this study was to investigate the short-term effect of hormone replacement therapy (HRT) on postural control in menopausal women and to analyse the correlation between sway velocity measures and results of functional balance tests. SUBJECTS: 100 menopausal women who were randomized to receive either HRT or placebo for three months were included in the study. METHOD: The balance function was measured with nine different static and dynamic functional balance tests. The sway velocities were measured on a computerized force platform. RESULTS: No significant differences were found between the two groups in the results of the functional balance tests after the three-month placebo-controlled period or in the changes over time. However, some significant improvements occurred within both groups over this three-month period. The correlations between different sway velocities and the results of the functional balance tests were all very low (r < 0.35). CONCLUSION: It can not be concluded that HRT had a positive effect on the performance in the functional balance tests, as some improvement occurred in both groups. The low correlations indicate that the sway velocity and functional balance tests measure different aspects of balance function.
Analysis of Variance↗
Nest attendance during egg laying in pheasants.
As precocial bird species hatch synchronously, incubation during the egg-laying stage should be disadvantageous because it makes the embryos develop asynchronously. We established the patterns of nest attendance during egg laying and the start of incubation in ring-necked pheasants, Phasianus colchicus, and tested three hypotheses regarding the advantage of early incubation. To determine nest attendance, we measured egg temperatures in real pheasant nests. Females spent more time on the nest as laying progressed, with an average of 6.4 h at a clutch size of 10. At the start of incubation, nest attendance increased to over 20 h/day. On the day before full incubation, time spent on the nest was positively correlated with the female's condition and negatively with the number of breeding attempts she had already made that season. The hypothesis that an early start of incubation improves egg viability was rejected, as the predicted relationship between the number of eggs laid after the start of incubation and the number laid before the start of incubation was not significant. We also rejected the possibility that early incubation reduces the risk of nest parasitism, as it was negatively related to the number of females radiotracked around the nest. Our data supported the hypothesis that early incubation reduces the risk of nest predation by shortening the period of exposure, as the number of eggs laid after incubation started was positively related to the number of breeding attempts made by the female, and thus to the perceived predation risk, but was negatively related to the time of season. Copyright 1999 The Association for the Study of Animal Behaviour.
Journal Article↗