PubMed Health⌕ Search

Biomedical subjects

A Auranen

Publications and source records attributed to A Auranen.

18 recordsLinked to original sources
PubMed2003

Common polymorphisms in checkpoint kinase 2 are not associated with breast cancer risk.

A substantial proportion of the familial risk of breast cancer may be attributable to genetic variants each contributing a small effect. Polymorphisms in DNA repair genes are good candidates for such low penetrance breast cancer susceptibility alleles. Checkpoint kinase 2 (CHEK2) is a kinase in which the yeast counterpart regulates a cell cycle checkpoint and causes cells to arrest proliferation after DNA damage. A rare, protein truncating mutation in the CHEK2 gene has recently been shown to confer a modest risk of breast cancer. The aim of this study was to determine whether common polymorphic variants in CHEK2 are associated with an increase in breast cancer risk. We assessed two variants in CHEK2 using a case control study design (n = 1786 cases and 1828 controls). No differences in genotype frequencies were found between cases and control for either the IVS1 + 38insa or the a1013g polymorphisms (P = 0.3 and 0.2 respectively), and no genotype-specific risk was significantly different from unity. The haplotype frequency distribution in cases and controls were also similar (P = 0.3). We conclude that the CHEK2 polymorphisms IVS + 1a and a1013g do not confer an increased risk of breast cancer. It is also unlikely that other, as yet unidentified, common polymorphisms that affect risk are present in the gene in the British population.

Breast Neoplasms↗
PubMed2001

BRCA1 and BRCA2 mutations among Finnish ovarian carcinoma families.

Germ-line mutations in BRCA1 and BRCA2 predispose to hereditary breast-ovarian cancer syndrome. In Finland, 21 different BRCA1/2 mutations have been identified and 14 of the mutations are founders that account for the great majority of all BRCA1/2 mutations. Our aim was to determine the prevalence of the 21 BRCA1/2 mutations in Finnish ovarian carcinoma families. Mutations were screened in 23 families with at least two cases of invasive epithelial ovarian carcinoma in the first-degree relatives. The families had been identified from a population-based series of 559 Finnish epithelial ovarian carcinoma patients. Fourteen of the families were site-specific ovarian carcinoma families, while breast cancer was present in nine families. Mutations were detected in five families: two had a mutation in BRCA1 and three in BRCA2. In one family, a novel, apparently disease-causing missense mutation in the BRCA2 gene had been identified previously. Thus, 26% of the Finnish ovarian carcinoma families were found to be BRCA1/2 mutation-positive. Strong ovarian cancer family history and early-onset breast cancer were strongly associated with BRCA1/2 mutation status; all families with three ovarian carcinoma cases or early-onset breast cancer (<50 years) were mutation-positive, whereas all families with later-onset breast cancer as well as the majority (9/11) of the site-specific ovarian carcinoma families with minor ovarian cancer history (i.e. two affected cases) remained mutation-negative.

Adult↗
PubMed1998

A missense mutation in the BRCA2 gene in three siblings with ovarian cancer.

Inherited susceptibility to ovarian cancer has been associated with germline defects at several loci. The major known ovarian cancer susceptibility gene is BRCA1 on chromosome 17q, which confers a risk of approximately 60% by the age of 70 years. Truncating mutations in BRCA2 on chromosome 13q also predispose to ovarian cancer, although they confer a lower risk than mutations in BRCA1. We have studied the molecular basis of ovarian cancer predisposition in a Finnish family with three affected sisters. Analysis of polymorphic markers provided evidence against linkage to BRCA1, but the sibship was consistent with linkage to BRCA2. Conformation-sensitive gel electrophoresis was used to screen the entire coding sequence of BRCA2. A G to A transition at nucleotide 8702 was observed, which is predicted to convert glycine 2901 to aspartate in the encoded protein. This sequence variant was not detected in 220 cancer-free Finnish control individuals, or in several hundred cancer families of many nationalities previously screened for BRCA2 mutations. Taken together with the fact that this amino acid residue and the surrounding region of BRCA2 is identical in mouse and chicken, the data suggest that this alteration is a disease-causing BRCA2 missense mutation. Previously published data indicate that the risks of breast and ovarian cancer conferred by BRCA2-truncating mutations varies with the position of the mutation in the gene. The missense mutation reported here suggests that the BRCA2 domain including and surrounding glycine 2901 may be more important in preventing neoplastic transformation in ovarian epithelium than in breast epithelium.

Adult↗
PubMed1998

Segregation analysis of epithelial ovarian cancer in Finland.

Epithelial ovarian cancer is known to aggregate in families. The dominantly inherited ovarian cancer predisposing genes, BRCA1, BRCA2 and genes involved in the hereditary non-polyposis colorectal cancer (HNPCC) syndrome, have recently been identified. However, in the majority of families with more than one case of ovarian cancer, dominant inheritance cannot be recognized. We investigated familial clustering of epithelial ovarian cancer in a population-based sample of 663 Finnish ovarian cancer patients. A segregation analysis with the POINTER software was conducted on the 937 nuclear families from these 663 pedigrees. The major gene model was favoured, and the sporadic and multifactorial models were strongly rejected. In the studied population, the best fitting model was a recessive mode of inheritance, and 8% of ovarian cancer patients were estimated to be homozygous for the deleterious genotype. This evidence for recessively inherited ovarian cancer predisposition should be interpreted cautiously, as the analysis is subject to certain errors, which are discussed in the article. Results of this analysis, however, strongly emphasize the role of genetic factors in all familial aggregation of epithelial ovarian cancer.

Adult↗
PubMed1997

Immunohistochemically detected p53 and HER-2/neu expression and nuclear DNA content in familial epithelial ovarian carcinomas.

BACKGROUND: Some epithelial ovarian carcinomas tend to occur more frequently in certain families. This clustering may be due to a genetic predisposition, but the role of inherited susceptibility in all families with multiple cases of ovarian carcinoma is currently unresolved. Studies characterizing familial ovarian carcinomas are few. METHODS: From a population-based study of 559 patients with epithelial ovarian carcinoma, 27 families with 2 or more ovarian carcinoma cases occurring in first-degree relatives were identified. Histopathology, ploidy, and immunohistochemically detected p53 and HER-2/neu expression in these tumors were examined. RESULTS: The mean age of the patients with familial ovarian carcinoma was 56.7 years. Approximately 67% of the tumors were either serous or undifferentiated adenocarcinomas. The percentage of aneuploid tumors was 46%, that of p53 positive tumors was 51%, and that of HER-2/neu positive tumors was 69%. When the families were divided into families with cases of breast carcinoma in addition to ovarian carcinoma cases and/or ovarian carcinoma in 2 consecutive generations (12 families) and families with ovarian carcinoma occurring in sisters only without cases of breast carcinoma (15 families), no differences were noted in the frequency of any of the studied variables. CONCLUSIONS: Familial ovarian carcinomas do not appear to differ from sporadic ovarian carcinomas with regard to patient age at presentation, histopathology, ploidy, and immunohistochemically detected p53 expression. Immunohistochemically detected HER-2/neu expression was found to occur more frequently in familial ovarian carcinomas than has been reported in sporadic ovarian carcinomas.

Adenocarcinoma↗
PubMed1997

PROGNOSTICATION OF BREAST CANCER BY MULTIVARIATE METHODS.

Three multivariate prognostic models based on Cox's regression were tested in terms of how they predicted prognosis in a material of 134 patients with breast cancer. The multivariate models all incorporated tumor size, mitotic activity index (MAI), and axillary lymph node status in their formulas, and were originally produced through studies on different patient materials. The predictive behavior of MAI was also tested separately in the same material. The multivariate models gave roughly parallel predicted percentages of survival at two years (CV=5.2%), but showed clearly greater variation later (12.3% and 24.4% at 5 and 9 years, respectively). The results were more uniform between the multivariate models, than between the prediction by MAI and the multivariate models. The variation between repeated estimates was smaller within multivariate models than within the estimation of one of their components (MAI). We found the use of the multivariate models easy. However, traditional hospital practice does not necessarily favor the use of multivariate models, although they seem to group patients more reliably than single prognostic features.

Journal Article↗
PubMed1996

Borderline ovarian tumors in Finland: epidemiology and familial occurrence.

A total of 1,197 borderline ovarian tumors were reported to the Finish Cancer Registry in 1973-1992. The mean age of the patients was 52 years, while the mean age of the 7,060 patients with an invasive epithelial ovarian carcinoma reported in the same time period was 62 years. The incidence of borderline ovarian tumors did not increase with age after patients became 35 years old and older. The overall age-adjusted incidence of borderline ovarian tumors was 1.8 per 100,000 women-years. Familial cancer occurrence during 1967-1992 was studied among relatives of 144 index patients diagnosed in 1980-1982. No borderline ovarian tumors were detected in the relatives, and only one of the 446 female first-degree relatives had an epithelial ovarian cancer. The expected number (borderline and invasive combined) was 1.9. The mothers of the index patients had an increased risk for pancreatic cancer (standardized incidence ratio 4.9, 95% confidence interval 1.0-14.3) and for cancer of the uterine cervix (standardized incidence ratio 7.8, 95% confidence interval 1.6-22.8). No significant increase in cancer risk was observed for fathers, brothers, or sisters of the patients with borderline ovarian tumors.

Adolescent↗
PubMed1996

Cancer incidence in the first-degree relatives of ovarian cancer patients.

Cancer incidence was studied among 3072 first-degree relatives of 559 unselected ovarian cancer patients. Among cohort members there were 306 cancer cases. The overall cancer incidence was not increased: the standardised incidence ratio (SIR) in males was 0.9 (95% confidence interval 0.8-1.1) and in females 1.0 (0.8-1.1). The female relatives had a significantly increased risk for ovarian cancer (SIR 2.8, 1.8-4.2). The excess was attributable to sisters only (SIR 3.7, 2.3-5.7). The relative risk for ovarian cancer among sisters decreased both by increasing age of the sister and by increasing age at diagnosis of the index patient: the SIRs were 7.3 (1.5-21.4), 4.5 (1.6-9.8) and 3.1 (1.7-5.4) for sisters of index patients diagnosed in age < 45, 45-54 and 55-75 years respectively. The age dependency of the risk supports the role of genetic factors in familial ovarian cancer. Although the risk of ovarian cancer among sisters from families with breast cancer (SIR 9.2, 3.7-19.0) was significantly higher than among sisters from families with no breast cancer patients (SIR 2.9, 1.6-4.8, rate ratio 3.1, P < 0.05), the excess was not solely attributable to coaggregation of breast and ovarian cancer. Among the 27 families with two or more ovarian cancers, only sisters were affected in 24 families, which might implicate recessive inheritance or shared environmental factors influencing ovarian cancer risk in sisters.

Adult↗
PubMed1975

The rate of drug biotransformation reactions and cellular viability in the livers of patients with biliary diseases.

The cytochrome P-450 level, the rate of o-amino-phenylglucuronide synthesis and the oxygen consumption of liver slices from female patients with various gall bladder disease were determined. The cytochrome P-450 level showed a decreasing trend in patients with chronic cholecystitis, choledocholithiasis or obstructive icterus when compared with those with uncomplicated gall bladder stones. The rate of o-aminophenylglucuronide synthesis was markedly increased in patients with obstructive icterus when compared with other groups. The oxygen consumption was also enhanced in this group. The enhanced rate of glucuronidation is suggested to be caused by endogenous induction of increased bilirubin level or by accumulation of bile acids in the liver cells. The present study proposes that the drug hydroxylation and glucuronidation activities are under separate control mechanisms.

Adult↗
PubMedDate not supplied

Hormonal treatments and epithelial ovarian cancer risk.

Exogenous sex hormones are widely used by women either for pregnancy prevention, as part of infertility treatment, or for treatment of menopausal symptoms. The role of these hormones in the development of ovarian cancer has been vastly explored. The protective effect of combined oral contraceptive pill is confirmed in multiple studies, but it is not clear whether this protection also covers women with a genetic predisposition to ovarian cancer. There is no conclusive evidence of infertility treatments increasing ovarian cancer risk, but infertility as such is a risk factor. Currently available data suggest that long-term users of hormone replacement therapy may have a slightly increased risk for ovarian cancer compared to women who have never used estrogen. The risk might particularly involve the endometrioid type of ovarian cancer. Most data on ovarian cancer and estrogen comes from epidemiological studies, since the normally high concentrations of estrogens in ovarian tissue and follicular fluid make direct biologic studies on the effects of exogenous estrogens on the ovarian cell difficult. This review discusses the risk of ovarian cancer associated with the use of sex steroid hormones, with special emphasis on the possible risk associated with estrogens.

Animals↗