| 1. |
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| 2. |
- Jakubowska, A, et al.
(författare)
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Association of PHB 1630 C andgt; T and MTHFR 677 C andgt; T polymorphisms with breast and ovarian cancer risk in BRCA1/2 mutation carriers: results from a multicenter study
- 2012
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Ingår i: British Journal of Cancer. - : Cancer Research UK / Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 106:12, s. 2016-2024
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The variable penetrance of breast cancer in BRCA1/2 mutation carriers suggests that other genetic or environmental factors modify breast cancer risk. Two genes of special interest are prohibitin (PHB) and methylene-tetrahydrofolate reductase (MTHFR), both of which are important either directly or indirectly in maintaining genomic integrity. less thanbrgreater than less thanbrgreater thanMETHODS: To evaluate the potential role of genetic variants within PHB and MTHFR in breast and ovarian cancer risk, 4102 BRCA1 and 2093 BRCA2 mutation carriers, and 6211 BRCA1 and 2902 BRCA2 carriers from the Consortium of Investigators of Modifiers of BRCA1 and BRCA2 (CIMBA) were genotyped for the PHB 1630 Candgt;T (rs6917) polymorphism and the MTHFR 677 Candgt;T (rs1801133) polymorphism, respectively. less thanbrgreater than less thanbrgreater thanRESULTS: There was no evidence of association between the PHB 1630 Candgt;T and MTHFR 677 Candgt;T polymorphisms with either disease for BRCA1 or BRCA2 mutation carriers when breast and ovarian cancer associations were evaluated separately. Analysis that evaluated associations for breast and ovarian cancer simultaneously showed some evidence that BRCA1 mutation carriers who had the rare homozygote genotype (TT) of the PHB 1630 Candgt;T polymorphism were at increased risk of both breast and ovarian cancer (HR 1.50, 95% CI 1.10-2.04 and HR 2.16, 95% CI 1.24-3.76, respectively). However, there was no evidence of association under a multiplicative model for the effect of each minor allele. less thanbrgreater than less thanbrgreater thanCONCLUSION: The PHB 1630TT genotype may modify breast and ovarian cancer risks in BRCA1 mutation carriers. This association need to be evaluated in larger series of BRCA1 mutation carriers.
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| 6. |
- Bratt, O, et al.
(författare)
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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
- 1999
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Ingår i: British Journal of Cancer. - : Springer Science and Business Media LLC. - 0007-0920 .- 1532-1827. ; 81:4, s. 6-672
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 7. |
- Bratt, O, et al.
(författare)
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Clinical course of early onset prostate cancer with special reference to family history as a prognostic factor
- 1998
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Ingår i: European Urology. - 0302-2838. ; 34:1, s. 19-24
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 8. |
- Bratt, O, et al.
(författare)
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Familial and hereditary prostate cancer in southern Sweden. A population-based case-control study
- 1999
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Ingår i: European Journal of Cancer. - 0959-8049. ; 35:2, s. 7-272
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 9. |
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| 10. |
- Bratt, O, et al.
(författare)
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Risk perception, screening practice and interest in genetic testing among unaffected men in families with hereditary prostate cancer
- 2000
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Ingår i: European Journal of Cancer. - 0959-8049. ; 36:2, s. 235-241
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 11. |
- Bratt, O, et al.
(författare)
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Sons of men with prostate cancer : their attitudes regarding possible inheritance of prostate cancer, screening, and genetic testing
- 1997
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Ingår i: Urology. - 0090-4295. ; 50:3, s. 5-360
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 12. |
- Bratt, O, et al.
(författare)
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The risk of malignant tumours in first-degree relatives of men with early onset prostate cancer : a population-based cohort study
- 1997
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Ingår i: European Journal of Cancer. - 0959-8049. ; 33:13, s. 2237-2240
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 15. |
- Engel, C., et al.
(författare)
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Association of the variants CASP8 D302H and CASP10 V410I with breast and ovarian cancer risk in BRCA1 and BRCA2 mutation carriers
- 2010
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 19:11, s. 2859-2868
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Tidskriftsartikel (refereegranskat)abstract
- Background: The genes caspase-8 (CASP8) and caspase-10 (CASP10) functionally cooperate and play a key role in the initiation of apoptosis. Suppression of apoptosis is one of the major mechanisms underlying the origin and progression of cancer. Previous case-control studies have indicated that the polymorphisms CASP8 D302H and CASP10 V410I are associated with a reduced risk of breast cancer in the general population.Methods: To evaluate whether the CASP8 D302H (CASP10 V410I) polymorphisms modify breast or ovarian cancer risk in BRCA1 and BRCA2 mutation carriers, we analyzed 7,353 (7,227) subjects of white European origin provided by 19 (18) study groups that participate in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). A weighted cohort approach was used to estimate hazard ratios (HR) and 95% confidence intervals (95% CI).Results: The minor allele of CASP8 D302H was significantly associated with a reduced risk of breast cancer (per-allele HR, 0.85; 95% CI, 0.76-0.97; Ptrend = 0.011) and ovarian cancer (per-allele HR, 0.69; 95% CI, 0.53-0.89; Ptrend = 0.004) for BRCA1 but not for BRCA2 mutation carriers. The CASP10 V410I polymorphism was not associated with breast or ovarian cancer risk for BRCA1 or BRCA2 mutation carriers.Conclusions: CASP8 D302H decreases breast and ovarian cancer risk for BRCA1 mutation carriers but not for BRCA2 mutation carriers.Impact: The combined application of these and other recently identified genetic riskmodifiers could in the future allow better individual risk calculation and could aid in the individualized counseling and decision making with respect to preventive options in BRCA1 mutation carriers.
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| 16. |
- Hakansson, Sara, et al.
(författare)
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Moderate frequency of BRCA1 and BRCA2 germ-line mutations in Scandinavian familial breast cancer
- 1997
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Ingår i: American Journal of Human Genetics. - 0002-9297. ; 60:5, s. 1068-1078
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Tidskriftsartikel (refereegranskat)abstract
- Previous studies of high-risk breast cancer families have proposed that two major breast cancer-susceptibility genes, BRCA1 and BRCA2, may account for at least two-thirds of all hereditary breast cancer. We have screened index cases from 106 Scandinavian (mainly southern Swedish) breast cancer and breast-ovarian cancer families for germ-line mutations in all coding exons of the BRCA1 and BRCA2 genes, using the protein-truncation test, SSCP analysis, or direct sequencing. A total of 24 families exhibited 11 different BRCA1 mutations, whereas 11 different BRCA2 mutations were detected in 12 families, of which 3 contained cases of male breast cancer. One BRCA2 mutation, 4486delG, was found in two families of the present study and, in a separate study, also in breast tumors from three unrelated males with unknown family history, suggesting that at least one BRCA2 founder mutation exists in the Scandinavian population. We report 1 novel BRCA1 mutation, eight additional cases of 4 BRCA1 mutations described elsewhere, and 11 novel BRCA2 mutations (9 frameshift deletions and 2 nonsense mutations), of which all are predicted to cause premature truncation of the translated products. The relatively low frequency of BRCA1 and BRCA2 mutations in the present study could be explained by insufficient screening sensitivity to the location of mutations in uncharacterized regulatory regions, the analysis of phenocopies, or, most likely, within predisposed families, additional uncharacterized BRCA genes.
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| 17. |
- Ilinca, A., et al.
(författare)
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Whole-Exome Sequencing in 22 Young Ischemic Stroke Patients With Familial Clustering of Stroke
- 2020
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Ingår i: Stroke. - : Ovid Technologies (Wolters Kluwer Health). - 0039-2499 .- 1524-4628. ; 51:4, s. 1056-1063
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Tidskriftsartikel (refereegranskat)abstract
- Backgrounds and Purpose-Although new methods for genetic analyses are rapidly evolving, there are currently knowledge gaps in how to detect Mendelian forms of stroke. Methods-We performed whole-exome sequencing in 22 probands, under 56 years at their first ischemic stroke episode, from multi-incident stroke families. With the use of a comprehensive stroke-gene panel, we searched for variants in stroke-related genes. The probands' clinical stroke subtype was related to clinical characteristics previously associated with pathogenic variants in these genes. Relatives were genotyped in 7 families to evaluate stroke-gene variants of unknown significance. In 2 larger families with embolic stroke of unknown source, whole-exome sequencing was performed in additional members to examine the possibility of identifying new stroke genes. Results-Six of 22 probands carried pathogenic or possibly pathogenic variants in genes reported to be associated with their stroke subtype. A known pathogenic variant in NOTCH3 and a possibly pathogenic variant in ACAD9 gene were identified. A novel JAK2:c.3188G>A (p.Arg1063His) mutation was seen in a proband with embolic stroke of undetermined source and prothrombotic status. However, penetrance in the family was incomplete. COL4A2:c.3368A>G (p.Glu1123Gly) was detected in 2 probands but did not cosegregate with the disease in their families. Whole-exome sequencing in multiple members of 2 pedigrees with embolic stroke of undetermined source revealed possibly pathogenic variants in genes not previously associated with stroke, GPR142:c.148C>G (p.Leu50Val), and PTPRN2:c.2416A>G (p.Ile806Val); LRRC1 c.808A>G (p.Ile270Val), SLC7A10c.1294dupG (p.Val432fs), IKBKB: c.1070C>T (p.Ala357Val), and OXGR1 c.392G>A (p.Arg131His), respectively. Conclusions-Screening with whole-exome sequencing using a comprehensive stroke-gene panel may identify rare monogenic forms of stroke, but careful evaluation of clinical characteristics and potential pathogenicity of novel variants remain important. In our study, the majority of individuals with familial aggregation of stroke lacked any identified genetic causes.
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| 18. |
- Kristoffersson, Anders N., 1985-, et al.
(författare)
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Population pharmacokinetics of colistin and the relation to survival in critically ill patients infected with colistin susceptible and carbapenem-resistant bacteria
- 2020
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Ingår i: Clinical Microbiology and Infection. - : Elsevier BV. - 1198-743X .- 1469-0691. ; 26:12, s. 1644-1650
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVES: The aim was to analyse the population pharmacokinetics of colistin and to explore the relationship between colistin exposure and time to death.METHODS: Patients included in the AIDA randomized controlled trial were treated with colistin for severe infections caused by carbapenem-resistant Gram-negative bacteria. All subjects received a 9 million units (MU) loading dose, followed by a 4.5 MU twice daily maintenance dose, with dose reduction if creatinine clearance (CrCL) < 50 mL/min. Individual colistin exposures were estimated from the developed population pharmacokinetic model and an optimized two-sample per patient sampling design. Time to death was evaluated in a parametric survival analysis.RESULTS: Out of 406 randomized patients, 349 contributed pharmacokinetic data. The median (90% range) colistin plasma concentration was 0.44 (0.14-1.59) mg/L at 15 minutes after the end of first infusion. In samples drawn 10 hr after a maintenance dose, concentrations were >2 mg/L in 94% (195/208) and 44% (38/87) of patients with CrCL ≤120 mL/min, and >120 mL/min, respectively. Colistin methanesulfonate sodium (CMS) and colistin clearances were strongly dependent on CrCL. High colistin exposure to MIC ratio was associated with increased hazard of death in the multivariate analysis (adjusted hazard ratio (95% CI): 1.07 (1.03-1.12)). Other significant predictors included SOFA score at baseline (HR 1.24 (1.19-1.30) per score increase), age and Acinetobacter or Pseudomonas as index pathogen.DISCUSSION: The population pharmacokinetic model predicted that >90% of the patients had colistin concentrations >2 mg/L at steady state, but only 66% at 4 hr after start of treatment. High colistin exposure was associated with poor kidney function, and was not related to a prolonged survival.
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| 19. |
- Kristoffersson, Ulf, et al.
(författare)
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Brister i genetisk kunskap i vården?
- 2007
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Ingår i: Att forma vår framtid. Bioteknikens möjligheter och problem. - 9789189116900 ; , s. 109-109
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Bokkapitel (övrigt vetenskapligt/konstnärligt)
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| 20. |
- Kristoffersson, U., et al.
(författare)
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Fine needle aspiration biopsy: A useful tool in tumor cytogenetics with special reference to malignant lymphomas
- 1981
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Ingår i: Cancer Genetics and Cytogenetics. - 2210-7762. ; 4:1, s. 53-60
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Tidskriftsartikel (refereegranskat)abstract
- A method for chromosome analysis of malignant cells by means of fine needle aspiration biopsy has been developed. The method has some obvious advantages compared to conventional surgical biopsy. During a 1-year period 25 consecutive non-Hodgkin, non-Burkitt lymphoma biopsies from 19 patients have been studied. In 14 out of 21 lymph node biopsies chromosome analysis was successful; whereas, four biopsies of subcutaneous lymphomas were unsuccessful. © 1981.
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| 24. |
- Loman, N, et al.
(författare)
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Family history of breast and ovarian cancers and BRCA1 and BRCA2 mutations in a population-based series of early-onset breast cancer
- 2001
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 1460-2105 .- 0027-8874. ; 93:16, s. 23-1215
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: BRCA1 and BRCA2 are the two major susceptibility genes involved in hereditary breast cancer. This study was undertaken to provide reliable population-based estimates of genetic influence and to characterize the nature and prevalence of BRCA1 and BRCA2 germline mutations in early-onset breast cancer.METHODS: In a series comprising all women diagnosed with breast cancer under the age of 41 years in southern Sweden during 1990 through 1995 (n = 262), family history of cancer was evaluated in 95% (n = 250) of the case subjects and germline mutations in BRCA1 and BRCA2 were analyzed in 89% (n = 234). All statistical tests were two-sided.RESULTS: A total of 97 case subjects had at least one first- or second-degree relative with breast or ovarian cancer; 34 (14%; 95% confidence interval [CI] = 9.6% to 18%) cases had at least two first- or second-degree relatives, 22 (8.8%; 95%CI = 5.3% to 12%) had one first-degree relative, and 41 (16%; 95% CI = 12% to 21%) had one second-degree relative with either cancer. If two females affected with breast or ovarian cancer who were related through an unaffected male were also defined as first-degree relatives, then a higher number of case subjects, 120 (48%; 95% CI = 42% to 54%), had at least one first-degree or second-degree relative with breast or ovarian cancer. Sixteen (6.8%; 95% CI = 4.0% to 11%) BRCA1 mutation carriers and five (2.1%; 95% CI = 0.70% to 4.9%) BRCA2 mutation carriers were identified. Among case subjects with one first- or more than one first- or second-degree relative with breast or ovarian cancer, BRCA mutations were more frequent (P<.001) than among the case subjects without this degree of family history. BRCA mutations were also statistically significantly more common among women with bilateral breast cancer than among women with unilateral breast cancer (P =.002). BRCA mutations were more common among younger case subjects than among older ones (P =.0027).CONCLUSIONS: Almost half (48%) of women in southern Sweden with early-onset breast cancer have some family history of breast or ovarian cancer, and 9.0% of early-onset breast cancer cases are associated with a germline mutation in BRCA1 or BRCA2. Mutation carriers were more prevalent among young women, women with at least one first- or second-degree relative with breast or ovarian cancer, and women with bilateral breast cancer.
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| 25. |
- Malander, S, et al.
(författare)
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One in 10 ovarian cancer patients carry germ line BRCA1 or BRCA2 mutations : results of a prospective study in Southern Sweden
- 2004
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Ingår i: European Journal of Cancer. - : Elsevier BV. - 1879-0852 .- 0959-8049. ; 40:3, s. 422-428
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Tidskriftsartikel (refereegranskat)abstract
- At least 10% of all ovarian cancers are estimated to have a hereditary background. Hereditary breast-ovarian cancer (HBOC) due to mutations in the BRCA genes is a major cause of hereditary ovarian cancer, although its frequency and relationship to age and family history in unselected series of ovarian cancers is not completely known. We report here the results of a full mutational screening analysis for germ line BRCA1 and BRCA2 mutations in 161 patients with invasive epithelial ovarian carcinomas. Age at diagnosis ranged from 22 to 82 years (mean 59 years). Deleterious (frame-shift, nonsense and missense) mutations were detected in 13/161 (8%) of the patients and affected BRCA1 in 12 cases and BRCA2 in one case. Four additional missense variants (one in BRCA1 and three in BRCA2) with a possible association with an increased risk ovarian cancer were revealed, resulting in a total frequency of BRCA gene alterations of 17/161 (11%). The 13 patients with deleterious mutations had a mean age of 57 years (range 41-76 years) and only three of these patients were below 50 years of age. A family history of at least one breast cancer and/or ovarian cancer was reported in all but 1 of the patients with BRCA mutations compared with only 24% of patients without mutations. Our findings in this prospective study confirm approximately 1 in 10 patients with ovarian cancer carry a germ line BRCA gene mutation associated with HBOC, and also indicate that a large number of these patients are over 50 years of age at diagnosis.
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