Biomedical subjects

Jonas Manjer

Publications and source records attributed to Jonas Manjer.

14 recordsLinked to original sources

PubMed2007

Endogenous androgens and risk of epithelial ovarian cancer: results from the European Prospective Investigation into Cancer and Nutrition (EPIC).

Few epidemiologic studies have examined the hypothesis that circulating androgens are involved in the development of ovarian cancer. We investigated the association between prediagnostic serum levels of androgens and sex hormone-binding globulin (SHBG) and ovarian cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition cohort. One hundred and ninety-two ovarian cancer cases and 346 matched controls not using exogenous hormones at baseline blood donation were eligible for the study. Serum levels of testosterone, androstenedione, dehydroepiandrosterone sulfate, and SHBG were measured by direct immunoassays. Free testosterone (fT) was calculated according to mass action laws. Multivariate conditional logistic regression was used to estimate odds ratios adjusted for possible confounders. Overall, there was no association between serum concentrations of androgens or SHBG and ovarian cancer risk. In postmenopausal women, fT concentrations were inversely related to risk [highest versus lowest tertile odds ratio 0.45 (0.24-0.86); P(trend) = 0.01]. Among women diagnosed before the age of 55 years, there was a negative association with SHBG and a positive association with fT and ovarian cancer risk, although these associations were not statistically significant. The present study suggests that circulating androgens and SHBG levels are not strongly associated with ovarian cancer risk, although levels of fT may be associated with an increased risk among women diagnosed at relatively young age. The heterogeneity of results on the associations of fT with ovarian cancer risk in postmenopausal women deserves further investigation.

Adult↗

PubMed2006

Physical activity and breast cancer risk: the European Prospective Investigation into Cancer and Nutrition.

There is convincing evidence for a decreased risk of breast cancer with increased physical activity. Uncertainties remain, however, about the role of different types of physical activity on breast cancer risk and the potential effect modification for these associations. We used data from 218,169 premenopausal and postmenopausal women from nine European countries, ages 20 to 80 years at study entry into the European Prospective Investigation into Cancer and Nutrition. Hazard ratios (HR) from multivariate Cox regression models were calculated using metabolic equivalent value-based physical activity variables categorized in quartiles, adjusted for age, study center, education, body mass index, smoking, alcohol use, age at menarche, age at first pregnancy, parity, current oral contraceptive use, and hormone replacement therapy use. The physical activity assessment included recreational, household, and occupational activities. A total physical activity index was estimated based on cross-tabulation of these separate types of activity. During 6.4 years of follow-up, 3,423 incident invasive breast cancers were identified. Overall, increasing total physical activity was associated with a reduction in breast cancer risk among postmenopausal women (P(trend) = 0.06). Specifically, household activity was associated with a significantly reduced risk in postmenopausal (HR, 0.81; 95% confidence interval, 0.70-0.93, highest versus the lowest quartile; P(trend) = 0.001) and premenopausal (HR, 0.71; 95% confidence interval, 0.55-0.90, highest versus lowest quartile; P(trend) = 0.003) women. Occupational activity and recreational activity were not significantly related to breast cancer risk in both premenopausal and postmenopausal women. This study provides additional evidence for a protective effect of physical activity on breast cancer risk.

Adult↗

PubMed2006

Rate of over-diagnosis of breast cancer 15 years after end of Malmö mammographic screening trial: follow-up study.

OBJECTIVE: To evaluate the rate of over-diagnosis of breast cancer 15 years after the end of the Malmö mammographic screening trial. DESIGN: Follow-up study. SETTING: Malmö, Sweden. SUBJECTS: 42 283 women aged 45-69 years at randomisation. INTERVENTIONS: Screening for breast cancer with mammography or not (controls). Screening was offered at the end of the randomisation design to both groups aged 45-54 at randomisation but not to groups aged 55-69 at randomisation. MAIN OUTCOME MEASURES: Rate of over-diagnosis of breast cancer (in situ and invasive), calculated as incidence in the invited and control groups, during period of randomised design (period 1), during period after randomised design ended (period 2), and at end of follow-up. RESULTS: In women aged 55-69 years at randomisation the relative rates of over-diagnosis of breast cancer (95% confidence intervals) were 1.32 (1.14 to 1.53) for period 1, 0.92 (0.79 to 1.06) for period 2, and 1.10 (0.99 to 1.22) at the end of follow-up. CONCLUSION: Conclusions on over-diagnosis of breast cancer in the Malmö mammographic screening trial can be drawn mainly for women aged 55-69 years at randomisation whose control groups were never screened. Fifteen years after the trial ended the rate of over-diagnosis of breast cancer was 10% in this age group.

Age Factors↗

PubMed2006

Physical activity and risk of colon and rectal cancers: the European prospective investigation into cancer and nutrition.

We investigated several aspects of the role of physical activity in colon and rectal cancer etiology that remain unclear in the European Prospective Investigation into Nutrition and Cancer. This cohort of 413,044 men and women had 1,094 cases of colon and 599 cases of rectal cancer diagnosed during an average of 6.4 years of follow-up. We analyzed baseline data on occupational, household, and recreational activity to examine associations by type of activity, tumor subsite, body mass index (BMI), and energy intake. The multivariate hazard ratio for colon cancer was 0.78 [95% confidence interval (95% CI), 0.59-1.03] among the most active participants when compared with the inactive, with evidence of a dose-response effect (P(trend) = 0.04). For right-sided colon tumors, the risk was 0.65 (95% CI, 0.43-1.00) in the highest quartile of activity with evidence of a linear trend (P(trend) = 0.004). Active participants with a BMI under 25 had a risk of 0.63 (95% CI, 0.39-1.01) for colon cancer compared with the inactive. Finally, an interaction between BMI and activity (P(interaction) = 0.03) was observed for right-sided colon cancers; among moderately active and active participants with a BMI under 25, a risk of 0.38 (95% CI, 0.21-0.68) was found as compared with inactive participants with BMI >30. No comparable decreased risks were observed for rectal cancer for any type of physical activity for any subgroup analyses or interactions considered. We found that physical activity reduced colon cancer risk, specifically for right-sided tumors and for lean participants, but not rectal cancer.

Body Mass Index↗

PubMed2005

Expression and signaling activity of Wnt-5a/discoidin domain receptor-1 and Syk plays distinct but decisive roles in breast cancer patient survival.

PURPOSE: The loss of Wnt-5a, a G-protein-coupled receptor ligand, or Syk, an intracellular kinase, has in separate studies been associated with poor prognosis of breast cancer patients. Both proteins are involved in cell adhesion, a key event in epithelial cancer metastasis. Here, we have investigated whether Syk is part of the Wnt-5a/discoidin domain receptor-1 (DDR1) signaling pathway and if a signaling interaction of these proteins is important for breast cancer-specific survival. EXPERIMENTAL DESIGN: The signaling interactions between Wnt-5a/DDR1 and Syk were addressed in mammary cell lines. Their mRNA and protein levels and the respective clinical correlates were investigated in 94 cases of primary breast cancer. RESULTS: The expression of Wnt-5a and Syk correlated in four of five tumor cell lines. However, despite a constitutive association between Syk and the Wnt-5a-dependent adhesion receptor DDR1, we found no evidence of a Wnt-5a/DDR1-mediated activation of Syk. Instead, beta(1) integrins initiate the adhesion-induced activation of Syk. In tumors from breast cancer patients, the protein expression of Wnt-5a and Syk were differently regulated at the translational and transcriptional level, respectively. Analysis of breast cancer-specific survival revealed that the presence of Wnt-5a and Syk in primary tumors has good predictive value for a favorable outcome. Intriguingly, a simultaneous loss of both proteins did not reduce survival more than loss of either. CONCLUSIONS: Despite the difference in regulation of Wnt-5a and Syk protein expression and their lack of signaling interaction, our clinical data indicate that a favorable prognosis in breast cancer requires the expression and signaling activity of both.

Breast Neoplasms↗

PubMed2005

Smoking as a determinant for plasma levels of testosterone, androstenedione, and DHEAs in postmenopausal women.

The aim of the present study was to investigate whether current smoking, ex-smoking, or amount of current smoking among postmenopausal women was associated with plasma levels of testosterone, and rostenedione, and DHEAs. About 65,000 women in Sweden have participated in two population-based prospective cohort studies where blood samples were collected at baseline, and information on life-style, reproductive history and anthropometrical measurements were available. The present study was based on 407 control subjects from a previous nested case-control study on the relation between steroid hormone levels and risk of breast cancer. A multivariate logistic regression analysis, adjusted for potential confounders, was used in order to obtain odds ratios (OR) with 95% confidence intervals. There was a high risk of high testosterone levels (above the median) in current vs. never smokers, OR: 1.85 (1.06-3.23). Risk of high testosterone levels increased by amount of daily smoking (increments of 10 cigarettes/day), OR: 1.55 (1.02-2.37). Ex-smoking was associated with high testosterone levels, OR: 1.56 (0.98-2.47). Current smoking and increasing amount of current smoking were weakly associated with high androstenedione levels. However, these associations did not reach statistical significance. No association was seen between smoking habits and DHEAs levels. We conclude that current smoking, and increasing amount of daily smoking, is associated with high testosterone levels.

Aged↗

PubMed2004

Smoking is associated with postmenopausal breast cancer in women with high levels of estrogens.

We investigated the association between smoking and risk of postmenopausal breast cancer in groups defined by high levels of estrogens, a factor known to enhance tumour progression. Two prospective cohorts of Swedish women provided 260 postmenopausal breast cancer cases and 514 controls. Blood samples were collected at baseline, and anthropometry, life-style factors and reproductive history had been assessed. Subjects were classified into quartiles with regard to the level of estrone, and into three categories with regard to estradiol. All analyses of the relation between smoking and breast cancer were repeated in different categories of these hormones. Logistic regression analysis, adjusted for matching factors, i.e., age at baseline, storage time and sub-cohort, yielded odds ratios (OR) with 95% confidence intervals (CI). Ever-smoking was associated with breast cancer in the top category of estrone, 2.02 (1.17-3.49). The highest risk was seen among ex-smokers, 2.96 (1.53-5.75). The pattern was similar for estradiol. Recent smoking cessation was associated with a high OR in top categories of estrone, 4.38 (1.27-15.2) and estradiol 10.0 (1.14-88.7). Smoking initiation before the age of 20 was associated with breast cancer in the top category of estrone, 2.73 (1.27-5.91). Several potential confounders were introduced into the statistical model, but none remained using backward selection. We conclude that ever-smoking was associated with the risk of breast cancer in women with high levels of estrone, and that ex-smoking was associated with breast cancer in women with high levels of estrone or estradiol.

Aged↗

PubMed2004

Non-attendance in breast cancer screening is associated with unfavourable socio-economic circumstances and advanced carcinoma.

Our first objective was to assess changes in non-attendance, proportion of advanced breast cancer and survival in Malmö Mammographic Service Screening Program, MMSSP, compared to a former trial, Malmö Mammographic Screening Trial, MMST. Our second objective was to describe non-attenders in MMSSP in socio-economic terms and risk for advanced breast cancer compared to attenders. Information from hospital and national registers was used to identify 33,800 women invited to service screening in MMSSP 1990-93. Attendance rates at first screening, the proportion of advanced breast cancers (Stage II-IV) and survival among non-attenders in MMSSP were compared to the non-attenders and with the control group of the former trial, MMST. Various socio-economic factors were assessed as potential predictors of non-attendance in MMSSP. Odds ratios (OR) and 95% confidence interval (CI) were computed. Incidence of breast cancer during a 10-year-period, relative risks and 95% CI among non-attenders compared to attenders in MMSSP were computed. Attendance rates were significantly lower in MMSSP but a lower proportion of advanced breast cancers and a somewhat better survival among breast cancer cases (not significant) was seen in non-attenders in MMSSP compared to MMST. In MMSSP non-attendance was associated with being unmarried, being born abroad, being not currently employed, crowded housing conditions and low income. Incidence of advanced breast cancer was significantly higher among non-attenders than among attenders. Attendance has decreased over time and potential reasons are discussed. Stage distribution and survival among non-attenders seem to have improved. Several socio-economic factors predict non-attendance and non-attenders are at higher risk for advanced breast cancer.

Aged↗

PubMed2004

Trends in incidence of acute pancreatitis in a Swedish population: is there really an increase?

BACKGROUND AND AIMS: Recent reports have suggested an increasing incidence of acute pancreatitis, and changing patterns of risk factors, over the past decades. The aim of this study was to investigate trends in the incidence of acute pancreatitis, and risk factors related to the disease, in a general population over a 15-year period. METHODS: Clinical, autopsy, and forensic records for all patients with a first attack of acute pancreatitis in Malmö, Sweden, from 1985 to 1999, were validated retrospectively. Evidence for diagnosis was reconsidered and plausible cause was assessed. The incidence of gallstone disease, lung cancer, and alcohol-related conditions in the background population were retrieved from hospital diagnosis records and cancer and cause-of-death registries. RESULTS: A total of 929 first attacks of acute pancreatitis were identified. The total incidence of acute pancreatitis increased by 3.9% per year (95% confidence interval [CI], 2.1-5.8). The incidence of gallstone-related pancreatitis increased by 7.6% per year (95% CI, 4.0-11.4), and this correlated with an increase in the incidence of other gallstone-related conditions ( r = 0.68; P = 0.005). Alcohol-related pancreatitis decreased by -5.1% per year (95% CI, -7.4 to -2.8), and this correlated with a decrease in the incidence of delirium tremens ( r = 0.75; P = 0.001), mortality from cirrhosis ( r = 0.81; P < 0.001), and incidence of lung cancer ( r = 0.57; P = 0.026). CONCLUSIONS: There was a statistically significant increase in the incidence of acute pancreatitis. Gallstone-related pancreatitis increased, and alcohol-related pancreatitis decreased. Both of these trends were statistically significant and correlated with trends in the incidence of other conditions associated with either gallstone disease or alcohol abuse.

Acute Disease↗

PubMed2004

Validity of self-reported information on cancer: determinants of under- and over-reporting.

The first aim of the present study was to assess the validity of self-reported information concerning previous cancer. The second aim was to investigate determinants for under- and over-reporting of cancer. The Malmö Diet and Cancer Study is a prospective cohort study including 28,098 subjects. A questionnaire assessed lifestyle and medical conditions, e.g. previous cancer (yes/no). Cancer follow-up was made using the Swedish Cancer Registry (SCR). Questionnaire information concerning previous cancer was considered as test, and SCR information as golden standard (any tumour in the SCR, and specific sites were investigated). The validity analysis assessed agreement, sensitivity and specificity. Under- and over-reporting were studied in relation to lifestyle and socio-demographic factors. Sensitivity of the questionnaire in relation to malignant tumours was 0.82. It was 0.53 when cancer in situ of the breast and uterine cervix together with benign lesions of the urinary bladder and the nervous system were included in the cancer definition. Under- and over-reporting (in relation to malignant tumours) were more common among women and old people. Obesity, size of household, place of birth, smoking, social participation, educational level, type of employment, alcohol consumption and poor well-being was associated with under- or over-reporting in relation to at least one of the studied endpoints in either men or women. We conclude that there was a considerable disagreement between self-reported information and cancer registry data.

Aged↗

PubMed2003

Postmenopausal breast cancer risk in relation to sex steroid hormones, prolactin and SHBG (Sweden).

OBJECTIVE: High levels of sex steroid hormones and prolactin have been suggested to enhance breast cancer development. Low levels of SHBG may indicate high levels of (bio-available) steroid hormones. The present study investigates whether high levels of sex steroid hormones and prolactin, and/or low levels of SHBG, are associated with high breast cancer risk. METHODS: Blood samples were collected in about 65,000 women participating in two population-based prospective cohort studies in Sweden. Follow-up yielded 173 postmenopausal breast cancer cases who had not been exposed to HRT. Levels of estrone, estradiol, SHBG, FSH, prolactin, testosterone, androstenedione and DHEAs were analysed in cases and 438 controls. Logistic regression analysis yielded odds ratios (ORs), with 95% confidence intervals, adjusted for potential confounders. RESULTS: The risk of breast cancer was associated with the highest versus lowest quartiles of estrone, OR: 2.58 (1.50-4.44), estradiol (dichotomised: high versus low) (1.73: 1.04-2.88), and testosterone (1.87: 1.08-3.25). High risks, although not statistically significant, were seen for androstenedione (1.58: 0.92-2.72) and DHEAs (1.62: 0.89-2.72). No strong associations were seen between SHBG or prolactin and risk of breast cancer. CONCLUSIONS: High levels of estrone, estradiol, testosterone, and possibly androstenedione and DHEAs, in postmenopausal women are associated with a high risk of subsequent breast cancer.

Androstenedione↗

PubMed2002

Prospective study of IGF-I, IGF-binding proteins, and breast cancer risk, in northern and southern Sweden.

OBJECTIVE: To examine the possible relationships of breast cancer risk to prediagnostic plasma levels of insulin; insulin-like growth factor-I (IGF-I); and IGF-binding proteins -1, -2, and -3. METHODS: Within two prospective cohorts in Umeå and Malmö we measured plasma concentrations of insulin, IGF-I, and IGFBPs for a total of 513 incident breast cancer cases and 987 matched controls. RESULTS: Globally, risk was unassociated with levels of IGF-I, IGFBP-3, or IGF-I adjusted for IGFBP-3. When breaking down the analysis by subgroups of age at blood donation, an increase in risk was observed for increasing levels of IGF-I in women aged 55 or older, in the Umeå cohort only (odds ratios of 1.00, 1.73, 1.76, 1.90; Ptrend = 0.05). This effect weakened, however, when the analysis was restricted to subjects who did not use exogenous hormones for the treatment of menopausal symptoms. Levels of IGF-I and IGFBP-3 were not related to risk in younger women, recruited before age 50, contrary to observations from previous studies. In a subcohort where blood samples had been collected after at least four hours of fasting, breast cancer risk showed no clear associations with levels of insulin, IGFBP-1, or IGFBP-2. CONCLUSIONS: Our results do not confirm earlier findings of an association of plasma IGF-I levels with breast cancer risk especially in young women, but suggest a possible association with postmenopausal breast cancer risk, possibly among ERT/HRT users only. Our results do not support the hypothesis that elevated plasma insulin levels, and reduced levels of IGFBP-I and IGFBP-2, are associated with increased breast cancer risk.

Adult↗

PubMed2002

Invitation to a population-based cohort study: differences between subjects recruited using various strategies.

AIM: The present study compares subjects recruited to a population-based prospective cohort study by community versus personal invitation, and subjects responding late versus early to personal invitation. Subjects were compared with respect to sociodemographic characteristics, selected lifestyle factors, cancer incidence and mortality. METHODS: The Malmö Diet and Cancer Study recruited a total of 28,098 subjects between 1991 and 1996. Entire birth-year cohorts, born 1923-50, were recruited using community directed (passive) invitation, and a personal letter of invitation (active recruitment). Information on sociodemography and lifestyle was obtained using a self-administered questionnaire. Anthropometric measurements were assessed at a physical examination. Cancer incidence and cause of death were retrieved using record linkage with national registries. RESULTS: Subjects responding to community directed invitation were older, and more often females, than participants recruited using personal invitation. Furthermore, participants recruited through passive invitation had a comparably more favourable situation with regard to sociodemographic and lifestyle factors. They also had a lower frequency of prevalent disease, lower incidence of cancer and lower mortality. Contrary to this, men were more likely to respond late to a personal letter of invitation and late responders were also older, as compared with subjects responding early to personal invitation. Furthermore, those who responded late had a comparatively unfavourable socioeconomic situation and were characterized by a high prevalence of current smoking, obesity, weight change, and prevalent disease. CONCLUSIONS: Subjects who are recruited using different strategies in population-based cohort studies may have different sociodemographic and lifestyle characteristics, and may vary with regard to prevalent disease, cancer incidence and subsequent mortality.

Adult↗

PubMed2002

Incidence of cardiovascular disease, cancer and death in postmenopausal women affirming use of hormone replacement therapy.

AIM: The goal of this study was to evaluate the incidence of myocardial infarction, cancer and death in relation to use of hormone replacement therapy (HRT). METHODS: Nine years' follow up of an urban cohort of peri-/postmenopausal women was undertaken. Local and national registers were used for retrieval of events. RESULTS: The incidence of myocardial infarction per 1.000 person-years in users and non-users was 0.61 (5/962) and 2.20 (92/4759) respectively, adjusted relative risk (RR) 0.37; 95% confidence interval 0.15-0.90. Rates of mortality from cardiovascular disease and cancer were 0.36 and 1.10, p= 0.058, and 2.60 and 2.09, p=0.360 respectively. In terms of all-cause mortality the adjusted RR was 1.02; 0.69-1.52, incidence of cancer 1.28; 1.01-1.64, breast cancer 1.52; 1.01-2.28 and endometrial cancer 3.61; 1.54-8.46. CONCLUSIONS: Women affirming use of HRT had a lower incidence of myocardial infarction. Further studies are needed to assess whether the absence of effect on total mortality may be accounted for by an increased cancer risk.

Adult↗