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O Bratt

Publications and source records attributed to O Bratt.

At least 19 recordsLinked to original sources
PubMed2006

CHEK2*1100delC is not an important high-risk gene in families with hereditary prostate cancer in southern Sweden.

OBJECTIVE: CHEK2*1100delC is a frame-shifting germ-line mutation which abolishes the function of cell-cycle-checkpoint kinase 2 (chk2) and hence impairs the cells' response to DNA damage. This variant occurs in 1% of the general Western population but has been reported to be more common among patients with breast and prostate cancer. The aim of this study was to investigate the significance of CHEK2*1100delC as a possible high-risk gene for hereditary prostate cancer in the population of southern Sweden. MATERIAL AND METHODS: We screened for the CHEK2*1100delC variant in 419 men diagnosed with prostate cancer in southern Sweden, 145 of whom were sporadic cases that were divided into two subgroups depending on whether they were diagnosed before (n=64) or after (n=81) the age of 55 years. A further 126 men were classified as familial prostate cancer cases and 148 as hereditary prostate cancer cases. The control group consisted of 305 military conscripts aged 18 years (range 18-21 years). RESULTS: The CHEK2*1100delC variant was found in 1.2% of the cases (sporadic: 0.7%; familial: 1.6%; hereditary: 1.4%) and in 1.0% of the controls. CONCLUSION: The CHEK2 1100delC mutation is not a clinically important high-risk gene for hereditary prostate cancer susceptibility in the population of southern Sweden.

Aged↗
PubMed2003

Acupuncture fails to reduce but increases anaesthetic gas required to prevent movement in response to surgical incision.

BACKGROUND: Acupuncture is used for clinical pain relief but has not been evaluated under clinical anaesthesia. This study was designed to compare movement in response to surgical incision in anaesthetized patients subjected to electro-acupuncture (EA) or sham procedures. Our hypothesis was that EA stimulation would reduce the requirements for anaesthetic gas. METHODS: Forty-six healthy women, scheduled for laparoscopic sterilization at a Swedish county hospital, were randomized to have either the electro-acupuncture (n = 23) or sham (n = 23) procedure between the induction of general anaesthesia and the start of surgery. The minimal alveolar concentration (MAC) of sevoflurane required to prevent neck or major limb movements in response to surgical incision was determined in each group of patients. RESULTS: The MAC for sevoflurane was found to be higher in the group given acupuncture than in the control group (2.1 +/- 0.3% vs. 1.8 +/- 0.4%; P = 0.008). CONCLUSION: Electro-acupuncture given during general anaesthesia with sevoflurane failed to reduce but instead increased the clinical need for anaesthetic gas, possibly by reducing the anaesthetic effect of sevoflurane and/or by facilitating nociceptive transmission and/or reflex activity.

Adult↗
PubMed2002

Hereditary prostate cancer: clinical characteristics and survival.

PURPOSE: Hereditary prostate cancer accounts for 5% to 10% of all prostate cancer cases. We assessed clinical characteristics and survival in patients with hereditary prostate cancer MATERIALS AND METHODS: The study comprised 201 patients from 62 Swedish hereditary prostate cancer families and 402 controls with prostate cancer who were matched for age and calendar year at diagnosis, and the hospital where the diagnosis was made. Clinical data were obtained from the National Cancer Registry, Causes of Death Registry and medical records. RESULTS: Median age at the diagnosis of hereditary prostate cancer was 68 years, which was 6 years less than in patients with prostate cancer in the general population in Sweden. Distributions of tumor grade, symptoms at diagnosis and initial therapy were similar in hereditary prostate cancer cases and controls. More controls were classified with localized disease but it may have been due to methodological problems. Overall and cancer specific survival was similar in patients with hereditary prostate cancer and controls as well as in subgroup analyses including those with early onset and those diagnosed before 1990. Prostate cancer was the cause of death in 75% of patients with hereditary prostate cancer, in contrast to 55% with prostate cancer in the Swedish population. This difference was completely explained by the earlier age at the diagnosis of hereditary prostate cancer. CONCLUSIONS: Hereditary prostate cancer has an earlier onset than sporadic prostate cancer but this study did not indicate any other important difference in clinical characteristics or survival in patients with hereditary prostate cancer and those with sporadic prostate cancer. However, it cannot be excluded that individual hereditary prostate cancer genes may have specific biological characteristics.

Age of Onset↗
PubMed2001

Amplification of hypoxia-inducible factor 1alpha gene in prostate cancer.

Hypoxia-inducible factor 1 (HIF-1) is a transcription factor that regulates the expression of genes associated with adaptation to reduced oxygen pressure. Increased expression of HIF-1alpha gene (HIF1A) has been found in the majority of prostate carcinomas. In addition, the PC-3 prostate cancer cell line has been shown to express the gene even under normoxic conditions. By comparative genomic hybridization (CGH), we have earlier shown that the PC-3 cell line contains a high-level amplification in the chromosomal region harboring the HIF1A gene. Here, we first fine mapped the gene to locus 14q23 by fluorescence in situ hybridization (FISH). The gene was then shown to be highly amplified in the PC-3 cell line. Subsequently, the copy number of the HIF1A gene was studied in 5 other prostate cancer cell lines (LNCaP, DU-145, NCI-H660, Tsu-Pr, JCA-1) and in 117 prostate tumors representing both hormone-dependent and -refractory disease as well as primary and metastatic lesions. No high-level amplifications of the HIF1A gene were found. Additional copies of the gene were seen in all of the cell lines and in 36% of the tumors. There was no association between the tumor type and the copy number alterations of the gene. In conclusion, high-level amplification of the HIF1A gene may explain the overexpression of the gene in the PC-3 prostate cancer cell line. However, such high-level amplification seems to be very rare in prostate cancer.

Chromosome Mapping↗
PubMed2001

Amplification of EIF3S3 gene is associated with advanced stage in prostate cancer.

Gain of the long arm of chromosome 8 (8q) is one of the most common gains found in the advanced prostate cancer by comparative genomic hybridization. We have previously identified a putative target gene for the 8q gain, EIF3S3, that encodes a p40 subunit of eukaryotic translation initiation factor 3 (eIF3). Here, we studied the frequency of the EIF3S3 amplification in different stages of prostate cancer and co-amplification of EIF3S3 and oncogene MYC. In addition, prognostic utility of the EIF3S3 copy number alteration was evaluated. The analyses were done with fluorescence in situ hybridization and tissue microarray technology. High-level amplification of EIF3S3 was found in 11 of 125 (9%) of pT1/pT2 tumors, 12 of 44 (27%) of pT3/pT4 tumors, and 8 of 37 (22%) of lymph node metastases as well as in 26 of 78 (33%) and 15 of 30 (50%) of hormone refractory locally recurrent tumors and metastases, respectively. The amplification was associated with high Gleason score (P < 0.001). One of the 79 tumors with EIF3S3 amplification had only two copies of MYC, whereas all tumors with amplification of MYC had also amplification of EIF3S3 indicating common co-amplification of the genes. Gain of EIF3S3 was associated with poor cancer-specific survival in incidentally found prostate carcinomas (P = 0.023). In the analyses of prostatectomy-treated patients, the amplification was not statistically significantly associated with progression-free time. In conclusion, amplification of EIF3S3 gene is common in late-stage prostate cancer suggesting that it may be functionally involved in the progression of the disease.

Aged↗
PubMed2000

Risk perception, screening practice and interest in genetic testing among unaffected men in families with hereditary prostate cancer.

Approximately 5-10% of prostate cancer cases are caused by dominantly inherited susceptibility to the disease. Although advances have been made in research concerning the genetic mechanisms of hereditary prostate cancer, little is known about the psychological consequences for men at high risk of developing the disease. The aims of the present study were to examine risk perception, interest in genetic investigations, cancer-specific worry, and screening practice among unaffected men, aged 40-72 years old, with a pedigree consistent with hereditary prostate cancer and an estimated lifetime risk of prostate cancer of 35-45%. A questionnaire was sent by mail to 120 subjects, of whom 110 responded. Most of the men (n = 90, 82%) worried about having an inherited susceptibility to prostate cancer, and 34 (31%) claimed that worry about prostate cancer affected their daily life (3 (3%) fairly much, 31 (28%) slightly). As many as 40% of the study subjects perceived their lifetime risk of prostate cancer as 67% or more. Perceived high risk was associated with symptoms of depression and with cancer worry affecting daily living. Two-thirds of the men aged 50 years old or more were regularly screened for prostate cancer. Subjects with high levels of cancer-specific stress, as measured by the avoidance subscale of the Impact of Event Scale, were less likely to opt for screening. Almost all of the men (94%) were interested in presymptomatic genetic testing (84 (76%) "definitely yes" and 20 (18%) "probably yes"). We conclude that hereditary susceptibility to prostate cancer has significant psychological consequences although it rarely causes psychiatric morbidity. The present study underlines the importance of giving thorough, repeated information to men at high risk of prostate cancer.

Adult↗
PubMed1999

Familial and hereditary prostate cancer in southern Sweden. A population-based case-control study.

The objectives of this study were to investigate the effect of family history on prostate cancer risk, to estimate the incidence of hereditary prostate cancer in southern Sweden and to assess the reliability of self-reported family history of prostate cancer. The study included consecutive prostate cancer patients and age-matched control subjects from a geographically defined population. The controls consisted of 1 male patient with malignant melanoma or non-Hodgkin's lymphoma and 1 male from the community per prostate cancer case. Family history was assessed with questionnaires, and diagnoses of fathers and brothers of cases were validated by the Southern Swedish Regional Tumour Registry. Among fathers and brothers whose names and birth dates were available, 56 (92%) of the 61 reported prostate cancer diagnoses were verified. Fifteen per cent of 356 cases and 5.0% of 712 controls reported at least 1 case of prostate cancer among their brothers or fathers, giving a relative risk of 3.2 (95% confidence interval 2.1-5.1). The relative risk increased with decreasing age at diagnosis of the patient. Based on the pedigree, 3.1% of the 356 patients were classified as having hereditary prostate cancer. This proportion was significantly higher among patients diagnosed before the age of 60 years (7.1%) than among older patients (2.2%). We conclude that there is a substantially increased risk of prostate cancer for sons and brothers of prostate cancer patients. The risk increases with decreasing age at diagnosis of the patient as an effect of a higher prevalence of hereditary prostate among early onset cases. Furthermore, we found self-reported family history of prostate cancer to be a valid estimate of the true incidence of prostate cancer in fathers and brothers of men with prostate cancer.

Adult↗
PubMed1999

CAG repeat length in the androgen receptor gene is related to age at diagnosis of prostate cancer and response to endocrine therapy, but not to prostate cancer risk.

The length of the polymorphic CAG repeat in the N-terminal of the androgen receptor (AR) gene is inversely correlated with the transactivation function of the AR. Some studies have indicated that short CAG repeats are related to higher risk of prostate cancer. We performed a case-control study to investigate relations between CAG repeat length and prostate cancer risk, tumour grade, tumour stage, age at diagnosis and response to endocrine therapy. The study included 190 AR alleles from prostate cancer patients and 186 AR alleles from female control subjects. All were whites from southern Sweden. The frequency distribution of CAG repeat length was strikingly similar for cases and controls, and no significant correlation between CAG repeat length and prostate cancer risk was detected. However, for men with non-hereditary prostate cancer (n = 160), shorter CAG repeats correlated with younger age at diagnosis (P = 0.03). There were also trends toward associations between short CAG repeats and high grade (P = 0.07) and high stage (P = 0.07) disease. Furthermore, we found that patients with long CAG repeats responded better to endocrine therapy, even after adjusting for pretreatment level of prostate-specific antigen and tumour grade and stage (P = 0.05). We conclude that short CAG repeats in the AR gene correlate with young age at diagnosis of prostate cancer, but not with higher risk of the disease. Selection of patients with early onset prostate cancer in case-control studies could therefore lead to an over-estimation of the risk of prostate cancer for men with short CAG repeats. An association between long CAG repeats and good response to endocrine therapy was also found, but the mechanism and clinical relevance are unclear.

Adult↗
PubMed1998

Clinical course of early onset prostate cancer with special reference to family history as a prognostic factor.

OBJECTIVE: The aim of this study was to describe the clinical characteristics of early onset prostate cancer, with special reference to family history as a possible prognostic factor. MATERIAL AND METHODS: We identified all cases of prostate cancer diagnosed before the age of 51 in the Southern health care region in Sweden between 1958 and 1994. Clinical data were collected retrospectively from medical records. Data about family history of prostate cancer were also collected from the parish authorities and the Regional Cancer Registry. RESULTS: In all, 89 cases were included. The median time of follow-up was 17 years. During the time of follow-up, 65 patients died, 57 of whom died from prostate cancer. At diagnosis, 34% of the patients had localized, 22% had locally advanced, and 40% had metastatic tumours. The tumours were well differentiated in 30% of the cases, moderately differentiated in 38%, and poorly differentiated in 28%. Information on tumour grade and stage was missing in 3 cases. The cause-specific survival was 48% at 5 years and 29% at 10 years. The 18 patients with a family history of prostate cancer had a somewhat better prognosis than the patients with a negative family history, though the difference did not reach statistical significance (p = 0.08). CONCLUSIONS: Early onset prostate cancer is a serious disease with high mortality. The proportions of patients with poorly differentiated and metastatic tumours appeared to be larger than for cases diagnosed later in life, but this could be explained by selection bias since younger men may have a lower probability of having asymptomatic localized tumours diagnosed. Family history of prostate cancer was not significantly associated with prognosis.

Age of Onset↗
PubMed1997

Sons of men with prostate cancer: their attitudes regarding possible inheritance of prostate cancer, screening, and genetic testing.

OBJECTIVES: To study attitudes regarding possible inheritance of prostate cancer among sons of men with prostate cancer. METHODS: A questionnaire was sent to 69 men with prostate cancer and their 101 unaffected sons. All participants were also interviewed by telephone. Sociodemographic data were collected, as were data about the fathers' disease. RESULTS: The response rate was high; 100 sons (99%) and 65 fathers (94%) answered all questions. Sixty of the sons claimed they had worries about having an increased risk of prostate cancer due to possible inheritance. About 90% of the sons wanted to know whether prostate cancer was inheritable (66 definitely and 24 probably), were positively inclined to undergo screening (65 definitely and 27 probably), and to undergo genetic testing (50 definitely and 41 probably), provided there had been multiple cases of prostate cancer in their family. An interest to know whether prostate cancer could be inherited was more frequent among sons with less than 12 years of education, worries about inheritance, younger age, a father treated with curative intent, and with children of their own, especially if sons. Interest in genetic testing was associated with less than 12 years of education and with worries about inheritance. CONCLUSIONS: A large majority of healthy men with a family history of prostate cancer were interested in knowing whether the disease could be inherited and were positively inclined to undergo screening and genetic testing. Our findings indicate that genetic counseling and a screening program could have beneficial psychological effects in families with multiple cases of prostate cancer.

Adult↗
PubMed1997

The risk of malignant tumours in first-degree relatives of men with early onset prostate cancer: a population-based cohort study.

Previous studies have indicated that hereditary prostate cancer is common among men with early onset prostate cancer. The aim of this study was to investigate the incidence of malignant tumours in first-degree relatives of men with early onset prostate cancer. All prostate cancer cases diagnosed before the age of 51 years from 1958 to 1994 were identified in the population-based Swedish Cancer Register. The first-degree relatives of clinical cases were identified through parish data. Their vital status and cancer incidence were studied in the Swedish Cancer Register, the Cause of Death Register and the Census Register. The expected incidence of malignant tumours for the first-degree relatives were calculated using regional cancer register data. Cause-specific standardised incidence ratios (SIR) and 95% confidence intervals (CI) were calculated. The study included 423 first-degree relatives of 89 men with clinical prostate cancer. The first-degree relatives' SIR for malignant tumours was 0.99 (95% CI 0.78-1.23). The SIR for prostate cancer diagnosed at any age was 1.43 (95% CI 0.82-2.33), and 3.37 for first-degree relatives diagnosed before the age of 70 years (95% CI 1.36-6.94). There was no significantly increased risk of any non-prostatic malignant tumour. Only in five of the families did the pedigree show a pattern of hereditary prostate cancer. The first-degree relatives of men with early onset prostate cancer had more than a 3-fold increase in the risk of developing prostate cancer before the age of 70 years, but their total cancer risk was not increased. This study does not support the assumption that dominantly inherited susceptibility is a major cause of early onset prostate cancer.

Adult↗