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1.
Br J Cancer ; 102(11): 1665-9, 2010 May 25.
Article in English | MEDLINE | ID: mdl-20407437

ABSTRACT

BACKGROUND: We investigated whether elevation in serum cytomegalovirus (CMV) or Epstein-Barr virus (EBV) immunoglobulin G (IgG) antibody levels precedes the development of breast cancer. METHODS: A nested case-control study was carried out within the Janus Serum Bank cohort. Two serum samples, one taken at least 4 years before diagnosis (sample 2) and an earlier sample (sample 1) from 399 women with invasive breast cancer and from 399 controls, matched for date of blood samples and age were tested for CMV and EBV IgG antibodies. Odds ratios (ORs) with 95% confidence intervals (CIs) for CMV and EBV seroconversion between the samples and unit changes in IgG optical density (OD) examined as a continuous variable were calculated using conditional logistic regression. RESULTS: Eleven cases and three controls seroconverted for CMV IgG between the first and second blood samples, with an adjusted OR for CMV IgG seroconversion of 4.0 (95% CI=1.1-14.4). The risk of breast cancer, adjusted for parity, increased per unit difference in CMV OD between samples (OR=1.7, 95% CI=1.1-2.5). In an analysis restricted to parous cases and age-matched parous controls, the OR for CMV seroconversion for IgG between the two samples, adjusted for parity and age at first birth, was 9.7 (95% CI=1.2-77.3). The EBV seroconversion or change in EBV OD was not associated with risk of breast cancer. CONCLUSION: Our hypothesis that elevation in serum CMV IgG antibody levels precedes the development of breast cancer in some women is supported by the results of this study. Changes in EBV IgG antibody are not associated with risk of breast cancer.


Subject(s)
Breast Neoplasms/epidemiology , Carcinoma/epidemiology , Cytomegalovirus Infections/epidemiology , Epstein-Barr Virus Infections/epidemiology , Adult , Aged , Aged, 80 and over , Antibodies, Viral/blood , Breast Neoplasms/blood , Breast Neoplasms/complications , Breast Neoplasms/virology , Carcinoma/blood , Carcinoma/complications , Carcinoma/virology , Case-Control Studies , Cytomegalovirus/immunology , Cytomegalovirus Infections/blood , Cytomegalovirus Infections/complications , Cytomegalovirus Infections/diagnosis , Epstein-Barr Virus Infections/blood , Epstein-Barr Virus Infections/complications , Epstein-Barr Virus Infections/diagnosis , Female , Herpesvirus 4, Human/immunology , Humans , Immunoglobulin G/analysis , Immunoglobulin G/blood , Middle Aged , Parity , Pregnancy , Serologic Tests , Young Adult
2.
J Inherit Metab Dis ; 31 Suppl 2: S293-7, 2008 Dec.
Article in English | MEDLINE | ID: mdl-18500571

ABSTRACT

Wolcott-Rallison syndrome (WRS) (OMIM 226980) is a rare, autosomal recessive disorder with infancy-onset diabetes mellitus, multiple epiphyseal dysplasia, osteopenia, mental retardation or developmental delay, and hepatic and renal dysfunction as main clinical findings. Patients with WRS have mutations in the EIF2AK3 gene, which encodes the pancreatic eukaryotic translation initiation factor 2-alpha kinase 3. We report a female patient who developed insulin-requiring diabetes at 2.5 months of age. Multiple epiphyseal dysplasia was diagnosed at age 2 years. At age 5.5 years she developed a Reye-like syndrome with hypoketotic hypoglycaemia and renal and hepatic insufficiency and died. A partial autopsy showed fat infiltration in the liver and kidneys. Examination of urine by gas chromatography and mass spectrometry showed large amounts of C(6)-dicarboxylic acid (adipic acid), 3-hydroxy-C(8)-dicarboxylic acid, 3-hydroxy-C(10)-dicarboxylic acid, and 3-hydroxydecenedioic acid. Acetoacetate and 3-hydroxybutyrate were absent. The findings suggested a metabolic block in mitochondrial fatty acid oxidation, but lack of material precluded enzyme analyses. The clinical diagnosis of WRS was suggested in retrospect, and confirmed by sequencing of DNA extracted from stored autopsy material. The patient was compound heterozygous for the novel EIF2AK3 mutations c.1694_1695delAT (Y565X) and c.3044T > C (F1015S). Our data suggest that disruption of the EIF2AK3 gene may lead to defective mitochondrial fatty acid oxidation and hypoglycaemia, thus adding to the heterogeneous phenotype of WRS.


Subject(s)
Diabetes Mellitus, Type 1/diagnosis , Dicarboxylic Acids/urine , Hydroxy Acids/urine , Lipid Metabolism, Inborn Errors/etiology , Osteochondrodysplasias/diagnosis , Adipates/urine , Biomarkers/urine , Child, Preschool , DNA Mutational Analysis , Diabetes Mellitus/etiology , Diabetes Mellitus, Type 1/complications , Diabetes Mellitus, Type 1/enzymology , Diabetes Mellitus, Type 1/genetics , Diabetes Mellitus, Type 1/urine , Disease Progression , Epiphyses/abnormalities , Epiphyses/enzymology , Fatal Outcome , Female , Gas Chromatography-Mass Spectrometry , Hepatic Insufficiency/etiology , Humans , Infant , Lipid Metabolism, Inborn Errors/genetics , Lipid Metabolism, Inborn Errors/urine , Mutation , Osteochondrodysplasias/complications , Osteochondrodysplasias/enzymology , Osteochondrodysplasias/etiology , Osteochondrodysplasias/genetics , Osteochondrodysplasias/urine , Renal Insufficiency/etiology , eIF-2 Kinase/genetics
3.
Br J Cancer ; 91(10): 1829-34, 2004 Nov 15.
Article in English | MEDLINE | ID: mdl-15477862

ABSTRACT

The aims of the present study were to find the frequency of the most common BRCA1 mutations in women with ovarian tumours identified from a population-based cancer registry and in the general population, to estimate the relative risk of ovarian tumours among the mutation carriers, and to explore the value of using CA125 as a prediagnostic test. The study was designed as a nested case-control study within a cohort mainly consisting of participants in population-based health examinations. The data files of The Cancer Registry of Norway and the Janus serum bank were linked to identify cases with ovarian cancer and borderline tumours. Hereditary BRCA1 mutations were determined using archived serum samples and capillary electrophoresis. Altogether 478 ovarian cancer patients and 190 patients with borderline tumours were identified, and 1421 and 568 matching controls were selected. Odds ratios (OR) of developing ovarian cancer and borderline tumours in the presence of BRCA1 mutations and CA125 level were derived from conditional logistic regression models. Among the 478 ovarian cancer patients, 19 BRCA1 mutations were identified (1675delA, 1135insA, 816delGT and 3347delAG), none among the patients with borderline tumours. Only two of the 1989 controls were BRCA1 mutation carriers (0.10%). The risk of ovarian cancer among the mutation carriers was strongly elevated (OR=29, 95% CI=6.6-120). CA125 was a marker for ovarian cancer, but the sensitivity was low. This study showed that BRCA1 mutation carriers have a very high risk of ovarian cancer. However, since the prevalence of BRCA1 mutations in the Norwegian population was low, the proportion of ovarian cancers due to BRCA1 mutations seemed to be low, about 4%. The sensitivity of using CA125 only as a screening test for ovarian cancer was low.


Subject(s)
Genes, BRCA1 , Mutation , Ovarian Neoplasms/genetics , Adult , Aged , CA-125 Antigen/analysis , Case-Control Studies , Female , Humans , Middle Aged , Norway/epidemiology , Odds Ratio , Ovarian Neoplasms/epidemiology , Prognosis , Risk
4.
Eur J Cancer ; 40(7): 1058-65, 2004 May.
Article in English | MEDLINE | ID: mdl-15093583

ABSTRACT

This case-control study based in Nordic serum banks evaluated the joint effects of infections with genital human papillomavirus (HPV) types, and Chlamydia trachomatis in the aetiology of cervical squamous cell carcinoma. Through a linkage with the cancer registries, 144 cases were identified and 420 controls matched to them. Exposure to past infections was defined by the presence of specific IgG antibodies. The odds ratio (OR) for the second-order interaction of HPV16, HPV6/11 and C. trachomatis was small (1.0) compared to the expected multiplicative OR, 57, and the additive OR, 11. The interactions were not materially different among HPV16 DNA-positive squamous cell carcinomas. When HPV16 was replaced with HPV18/33 in the analysis of second-order interactions with HPV6/11 and C. trachomatis, there was no evidence of interaction, the joint effect being close to the expected additive OR. Possible explanations for the observed antagonism include misclassification, selection bias or a true biological phenomenon with HPV6/11 and C. trachomatis exposures antagonizing the carcinogenic effects of HPV16.


Subject(s)
Carcinoma, Squamous Cell/virology , Chlamydia Infections/complications , Papillomavirus Infections/complications , Uterine Cervical Neoplasms/microbiology , Adult , Carcinoma, Squamous Cell/epidemiology , Case-Control Studies , Cervix Uteri/microbiology , Cervix Uteri/virology , Chlamydia Infections/epidemiology , DNA, Viral/isolation & purification , Female , Finland/epidemiology , Humans , Middle Aged , Multivariate Analysis , Norway/epidemiology , Papillomaviridae/isolation & purification , Papillomavirus Infections/epidemiology , Regression Analysis , Risk Factors , Sweden/epidemiology , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/virology
5.
Br J Cancer ; 87(2): 175-80, 2002 Jul 15.
Article in English | MEDLINE | ID: mdl-12107839

ABSTRACT

Several prospective studies with invasive carcinoma as endpoint have supported Human Papillomavirus as a cause of cervical carcinoma. However, the largest study used seroepidemiology and did not analyse presence of Human Papillomavirus DNA in the subsequent tumour. Linkage of serum bank registries and cancer registries had identified 196 women with a registered cervical carcinoma after donation of a serum sample. For the present study, biopsies for 127 cases could be located, verified to contain invasive carcinoma and be amplified by PCR. Three control women who had remained alive and without cervical carcinoma during an equal length of follow-up had been matched to each of the case women and tested for HPV antibodies. Presence of Human Papillomavirus DNA in the tumours was analysed by general primer and type specific PCR. HPV16-seropositive women had a relative risk of 4.4 (95% CI: 2.2-8.8) to develop cervical carcinoma carrying HPV16 DNA. By contrast, there was no excess risk for Human Papillomavirus 16-seropositive women to develop cervical carcinoma devoid of HPV16 DNA. Prediagnostic HPV16 seropositivity was strongly correlated with later HPV16 DNA positivity of the tumour (P<0.001) and prediagnostic HPV18 seropositivity correlated with HPV18 DNA in the tumour (P<0.03). The link between prediagnostic seropositivity and type of viral DNA in the cancer implies that the carcinogenic effect of infection with these viruses is dependent on persistent presence of type-specific viral DNA.


Subject(s)
Antibodies, Viral/blood , Carcinoma, Squamous Cell/epidemiology , DNA, Viral/isolation & purification , Papillomaviridae/isolation & purification , Papillomavirus Infections/epidemiology , Precancerous Conditions/epidemiology , Tumor Virus Infections/epidemiology , Uterine Cervical Neoplasms/epidemiology , Adult , Carcinoma, Squamous Cell/virology , Case-Control Studies , DNA Probes, HPV , DNA, Viral/blood , Female , Finland/epidemiology , Follow-Up Studies , Humans , Mass Screening , Middle Aged , Norway/epidemiology , Papillomaviridae/classification , Papillomaviridae/genetics , Papillomaviridae/immunology , Papillomavirus Infections/diagnosis , Polymerase Chain Reaction , Precancerous Conditions/diagnosis , Pregnancy , Pregnancy Complications, Infectious/diagnosis , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/virology , Prospective Studies , Risk , Seroepidemiologic Studies , Tumor Virus Infections/diagnosis , Uterine Cervical Neoplasms/virology
6.
Br J Cancer ; 87(1): 61-4, 2002 Jul 01.
Article in English | MEDLINE | ID: mdl-12085257

ABSTRACT

Human papillomavirus has emerged as the leading infectious cause of cervical and other anogenital cancers. We have studied the relation between human papillomavirus infection and the subsequent risk of anal and perianal skin cancer. A case-cohort study within two large Nordic serum banks to which about 760 000 individuals had donated serum samples was performed. Subjects who developed anal and perianal skin cancer during follow up (median time of 10 years) were identified by registry linkage with the nationwide cancer registries in Finland and Norway. Twenty-eight cases and 1500 controls were analysed for the presence of IgG antibodies to HPV 16, 18, 33 or 73, and odds ratios of developing anal and perianal skin cancer were calculated. There was an increased risk of developing anal and perianal skin cancer among subjects seropositive for HPV 16 (OR=3.0; 95%CI=1.1-8.2) and HPV 18 (OR=4.4; 95%CI=1.1-17). The highest risks were seen for HPV 16 seropositive patients above the age of 45 years at serum sampling and for patients with a lag time of less than 10 years. This study provides prospective epidemiological evidence of an association between infection with HPV 16 and 18 and anal and perianal skin cancer.


Subject(s)
Anus Neoplasms/etiology , Anus Neoplasms/virology , Carcinoma, Squamous Cell/etiology , Carcinoma, Squamous Cell/virology , Papillomaviridae/pathogenicity , Papillomavirus Infections/complications , Registries , Tumor Virus Infections/complications , Adult , Age Factors , Aged , Antibodies, Viral/analysis , Anus Neoplasms/epidemiology , Carcinoma, Squamous Cell/epidemiology , Epidemiologic Studies , Female , Finland/epidemiology , Humans , Immunoglobulin G/analysis , Male , Middle Aged , Odds Ratio , Prospective Studies , Risk Factors
7.
Scand J Clin Lab Invest ; 61(6): 443-7, 2001.
Article in English | MEDLINE | ID: mdl-11681533

ABSTRACT

Stored sera from healthy persons can be used to study relationships between blood variables at the time of sampling and disease appearing several years later but storage may influence the variables. In this work we measured the concentration of albumin and free fatty acids (FFA) in samples from the JANUS serum bank of Norway. Sera from blood donors and persons participating in health screening programs have been added to the bank since 1973. The concentration of albumin and FFA was measured in 443 JANUS bank sera. The material was divided into quartiles according to the length of storage: <3 years (n = 110), 3-6 years (n = 110), 6-12 years (n = 115) and >12 years (n = 108). Albumin was measured colorometrically using the bromcresol green method and FFA was determined enzymatically. The serum albumin concentrations (mean +/- SEM) in the four groups were 55.8+/-0.6, 56.2+/-0.5, 59.9+/-0.6 and 59.5+/-0.6 g/L. The values of groups 3 and 4 were significantly higher than those of groups 1 and 2 (p<0.001). The serum FFA concentrations in the four groups were 0.56+/-0.03, 0.64+/-0.03, 0.77+/-0.03 and 0.85+/-0.04 mmol/L, i.e. a significant storage effect. The Scheffé multiple comparison test showed that FFA values in groups 3 and 4 were significantly higher than those in groups 1 and 2 (p <0.001 for group 4 vs. 1 and 2, and 3 vs. 1; p<0.04 for group 3 vs. 2) Serum FFA and albumin levels were positively associated (r = 0.489, p <0.01). Using linear regression analysis, it was estimated that serum albumin values increased by 0.28 g/L per year (i.e. 0.5%) and FFA by 0.02 mmol/L (i.e. 3.8%). Thus, measured by standard methods, serum FFA and albumin could increase in response to several years of storage at -25 degrees C. It is suggested that the storage time dependent increase in FFA is due to FFA liberation from lipoprotein triglycerides, whereas the apparent increase in albumin concentration possibly could be attributed to an unfolding of the protein, allowing more bromcresol green to be bound.


Subject(s)
Blood Preservation , Fatty Acids, Nonesterified/blood , Serum Albumin/analysis , Specimen Handling , Humans
8.
J Chromatogr A ; 914(1-2): 265-75, 2001 Apr 20.
Article in English | MEDLINE | ID: mdl-11358221

ABSTRACT

Urine and blood samples from patients with known metabolic disorders have been analyzed by CE, MS-MS and CE-MS-MS. For the identification of defects in acylcarnitine metabolism, blood spots on filter paper were analyzed using an MS-MS "neonatal screening" approach. Direct CE-MS-MS analysis was used for the analysis of urine samples from patients with different metabolic disorders, including galactosemia, neuroblastoma, Zellweger syndrome, propionic acidemia and alcaptonuria. The sensitivity of the CE-MS-MS method was increased by use of multiple reaction monitoring.


Subject(s)
Electrophoresis, Capillary/methods , Mass Spectrometry/methods , Metabolism, Inborn Errors/diagnosis , Neonatal Screening/methods , Humans , Infant, Newborn , Metabolism, Inborn Errors/blood , Metabolism, Inborn Errors/urine , Reproducibility of Results
9.
N Engl J Med ; 344(15): 1125-31, 2001 Apr 12.
Article in English | MEDLINE | ID: mdl-11297703

ABSTRACT

BACKGROUND: Oncogenic human papillomaviruses (HPVs), especially HPV type 16 (HPV-16), cause anogenital epithelial cancers and are suspected of causing epithelial cancers of the head and neck. METHODS: To examine the relation between head and neck cancers and HPVs, we performed a nested case-control study within a joint Nordic cohort in which serum samples were collected from almost 900,000 subjects. Samples collected at enrollment from 292 persons in whom squamous-cell carcinoma of the head and neck developed, on average, 9.4 years after enrollment and from 1568 matched controls were analyzed for antibodies against HPV-16, HPV-18, HPV-33, and HPV-73 and for cotinine levels as a marker of smoking habits. Polymerase-chain-reaction (PCR) analyses for HPV DNA were performed in tumor tissue from 160 of the study patients with cancer. RESULTS: After adjustment for cotinine levels, the odds ratio for squamous-cell carcinoma of the head and neck in subjects who were seropositive for HPV-16 was 2.2 (95 percent confidence interval, 1.4 to 3.4). No increased risk was observed for other HPV types. Fifty percent of oropharyngeal and 14 percent of tongue cancers contained HPV-16 DNA, according to PCR analysis. CONCLUSIONS: HPV-16 infection may be a risk factor for squamous-cell carcinoma of the head and neck.


Subject(s)
Antibodies, Viral/blood , Carcinoma, Squamous Cell/virology , Head and Neck Neoplasms/virology , Papillomaviridae , Papillomavirus Infections/complications , Tumor Virus Infections/complications , Adult , Carcinoma, Squamous Cell/blood , Case-Control Studies , Cohort Studies , Cotinine/blood , Female , Head and Neck Neoplasms/blood , Humans , Male , Middle Aged , Odds Ratio , Papillomaviridae/classification , Papillomaviridae/immunology , Risk Factors
10.
JAMA ; 285(1): 47-51, 2001 Jan 03.
Article in English | MEDLINE | ID: mdl-11150108

ABSTRACT

CONTEXT: Human papillomavirus (HPV) infection has been established as a cause of cervical cancer. Epidemiologic studies suggest that Chlamydia trachomatis infection also confers increased risk for cervical squamous cell carcinoma (SCC). Whether this risk is serotype-specific is unknown. OBJECTIVE: To study the association between exposure to different C trachomatis serotypes and subsequent development of cervical SCC. DESIGN AND SETTING: Longitudinal, nested case-control study within a cohort of 530 000 women who provided samples to serum banks in Finland, Norway, and Sweden. The data files were linked to respective national cancer registries. SUBJECTS: One hundred twenty-eight women who had developed invasive cervical SCC at least 12 months following serum donation. Each case had 3 matched controls. MAIN OUTCOME MEASURE: Risk for the development of cervical SCC by IgG antibodies to 10 different C trachomatis serotypes, adjusted for antibodies to HPV types 16, 18, and 33 and for serum cotinine levels. RESULTS: Of specific C trachomatis serotypes, serotype G was most strongly associated with SCC (adjusted odds ratio [OR], 6.6; 95% confidence interval [CI], 1. 6-27.0). Other serotypes associated with SCC were I (OR, 3.8; 95% CI, 1.3-11.0) and D (OR, 2.7; 95% CI, 1.3-5.6). Presence of serum IgG antibodies to more than 1 serotype increased the adjusted ORs for SCC (P<.001 for trend). CONCLUSIONS: Chlamydia trachomatis serotype G is most strongly associated with subsequent development of cervical SCC. Increasing numbers of exposures to different C trachomatis serotypes also increases risk. Our results strengthen the evidence that there is a link between past C trachomatis infection and cervical SCC.


Subject(s)
Carcinoma, Squamous Cell/microbiology , Chlamydia trachomatis/classification , Uterine Cervical Neoplasms/microbiology , Antibodies, Bacterial/blood , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/epidemiology , Carcinoma, Squamous Cell/virology , Case-Control Studies , Chlamydia Infections/complications , Chlamydia trachomatis/genetics , Chlamydia trachomatis/immunology , Cotinine/blood , DNA, Bacterial , Female , Humans , Logistic Models , Longitudinal Studies , Papillomaviridae/isolation & purification , Registries , Risk Factors , Scandinavian and Nordic Countries/epidemiology , Serotyping , Uterine Cervical Neoplasms/blood , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/virology
11.
Cancer Causes Control ; 11(9): 783-90, 2000 Oct.
Article in English | MEDLINE | ID: mdl-11075866

ABSTRACT

OBJECTIVES: To estimate the joint effects of infections with human papillomavirus type 16 (HPV16) and Chlamydia trachomatis and smoking on the risk of cervical cancer. To study whether the joint effects can be accounted for by misclassification in the HPV serology. METHODS: A nested case-control study with incidence density sampling was conducted in three cohorts of 530,000 women, who donated serum samples to three Nordic serum banks in 1973-1994. The main outcome measure is the odds ratio (OR) of incidence rates of invasive cervical squamous cell carcinoma (SCC) among those seropositive for HPV16 and/or C. trachomatis and/or with increased levels of cotinine in serum compared to those negative for all the three exposures. RESULTS: Two hundred eight women with SCC and 624 matched controls were identified during a mean follow-up of 5 years through linkage to the national cancer registries. Exposure to past infections and smoking was defined by presence of specific IgG antibodies to HPV16 and C. trachomatis and increased levels of serum cotinine. Observed ORs were compared to OR = 20 for HPV16 and accounting the differences for by misclassification bias. OR = 20 was elected as a gold standard on the basis of other studies with PCR-based analyses and a follow-up design. Each of the three exposures was associated with an increased risk of SCC (OR = 5.4 for HPV16, 3.4 for C. trachomatis and 1.8 for cotinine). The interaction was antagonistic (observed OR = 2.5 among those positive for all three exposures as compared to OR = 33 expected on the basis of multiplicative single effects (p = 0.047)). The antagonism could not totally be accounted for by any credible combination of sensitivity and specificity of HPV16 serology. CONCLUSION: HPV16, C. trachomatis, and smoking are likely to be risk factors of SCC with strong antagonistic joint effect. Non-differential misclassification in serology for HPV16 could be ruled out (but only some types of differential) as an alternative explanation for the observed antagonism.


Subject(s)
Antibiosis , Chlamydia Infections/complications , Chlamydia trachomatis/classification , Chlamydia trachomatis/virology , Papillomaviridae/classification , Papillomavirus Infections/complications , Smoking/adverse effects , Tumor Virus Infections/complications , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/virology , Antibodies, Viral/blood , Case-Control Studies , Cohort Studies , Female , Finland , Follow-Up Studies , Humans , Norway , Odds Ratio , Pregnancy/physiology , Risk Factors , Sensitivity and Specificity , Sweden
12.
Acta Neurochir (Wien) ; 142(9): 1025-30, 2000.
Article in English | MEDLINE | ID: mdl-11086812

ABSTRACT

BACKGROUND: Bilateral, temporal arachnoid cysts are common in patients with Glutaric aciduria type 1 (GAT1). The present study investigates whether bitemporal cysts may occur unrelated to GAT1. and it reports our experience with 2 GAT1 patients. METHODS: During the last 11 years, the regional neurosurgical department has seen a total of 147 patients with arachnoid cysts in a population of 890,000. Eight of these patients had bitemporal arachnoid cysts, 4 boys, 3 adult females, and 1 adult male. Urine from 7 of these patients was examined with gas chromatography-mass spectrometry. FINDINGS: Large amounts of glutaric acid were discovered in the urine of only 2 of these patients, both young boys with severe neurological symptoms of the disease. One of them died 2 years after the clinical start of the disease. The remaining 5 urinary specimens contained low (normal) concentrations of glutaric acid. INTERPRETATION: For neurosurgeons, it is important to recognise that children with bitemporal arachnoid cysts may have GAT1, and that even simple surgical procedures may be extremely harmful for such patients. All paediatric patients with bitemporal arachnoid cysts should therefore be screened for GAT1 before any surgical procedure takes place, especially if there is also macrocephaly, an acute encephalitis-like illness, or a dystonic, cerebral palsy-like condition. It is concluded that bitemporal arachnoid cysts are extremely rare, and that they may well occur unrelated to GAT1.


Subject(s)
Arachnoid Cysts/complications , Glutarates/urine , Metabolism, Inborn Errors/complications , Neurosurgical Procedures , Oxidoreductases Acting on CH-CH Group Donors , Oxidoreductases/deficiency , Adult , Aged , Arachnoid Cysts/surgery , Arachnoid Cysts/urine , Contraindications , Fatal Outcome , Female , Glutaryl-CoA Dehydrogenase , Humans , Infant , Male , Metabolism, Inborn Errors/enzymology , Metabolism, Inborn Errors/urine , Severity of Illness Index , Temporal Lobe/pathology , Treatment Outcome
14.
Cancer Epidemiol Biomarkers Prev ; 9(12): 1357-67, 2000 Dec.
Article in English | MEDLINE | ID: mdl-11142422

ABSTRACT

This study investigated the potential association between organochlorine exposure and breast cancer using stored sera collected from 1973 through 1991 from the Janus Serum Bank in Norway. Breast cancer cases were ascertained prospectively from among 25,431 female serum bank donors. A total of 150 controls were matched to cases by birth dates and dates of sample collection. One g of serum per subject was analyzed for a total of 71 organochlorine compounds. For 6 pesticides [B-hexachlorocyclohexane, heptachlor epoxide, oxychlordane, trans-nonachlor, p, p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene, and p, p'-2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane] and 26 individual polychlorinated biphenyl (PCB) congeners there were >90% of samples over the limit of detection. There was no evidence for higher mean serum levels among cases for any of these compounds, nor any trend of increasing risk associated with higher quartiles of exposure. The remaining compounds (including dieldrin) were analyzed with respect to the proportion of cancer cases and controls having detectable levels; no positive associations were noted in these analyses. Our study did not confirm the recent findings of a Danish study of increased concentrations of dieldrin in the serum of breast cancer cases. The evidence to date on the association between serum organochlorines is not entirely consistent, but there is accumulating evidence that serum levels of p, p'-1,1-dichloro-2,2-bis(p-chlorophenyl)ethylene and total PCBs are not important predictors for breast cancer in the general population. Studies to date have not been able to evaluate whether exposure to highly estrogenic, short-lived PCB congeners increases breast cancer risk, nor have they fully evaluated the risk associated with organochlorine exposure in susceptible subgroups or at levels above general population exposure, including women with occupational exposure.


Subject(s)
Adenocarcinoma/blood , Breast Neoplasms/blood , Insecticides/blood , Adenocarcinoma/chemically induced , Adolescent , Adult , Age Factors , Blood Banks/statistics & numerical data , Breast Neoplasms/chemically induced , Case-Control Studies , Female , Humans , Middle Aged , Norway , Polychlorinated Biphenyls/blood , Prospective Studies , Receptors, Estrogen/analysis , Receptors, Progesterone/analysis , Regression Analysis
15.
Int J Cancer ; 85(1): 35-9, 2000 Jan 01.
Article in English | MEDLINE | ID: mdl-10585579

ABSTRACT

Cervical carcinoma is a sexually transmitted disease most strongly linked with human-papillomavirus (HPV) infection. We conducted a prospective sero-epidemiologic study to evaluate the role of Chlamydia trachomatis infection in the development of cervical carcinoma, with invasive cancer as an end point. A nested case-control study within a cohort of 530000 Nordic women was performed. Linking data files of 3 Nordic serum banks and the cancer registries of Finland, Norway and Sweden identified 182 women with invasive cervical carcinoma diagnosed during a mean follow-up of 5 years after serum sampling. The serum samples of the cases and matched cancer-free controls were analyzed for IgG antibodies to C. trachomatis, C. pneumoniae (a control microbe) and HPV types 16, 18 and 33, as well as for serum cotinine (an indicator of tobacco smoking). Serum antibodies to C. trachomatis were associated with an increased risk for cervical squamous-cell carcinoma (HPV- and smoking-adjusted OR, 2.2; 95% CI, 1.3-3.5). The association remained also after adjustment for smoking both in HPV16-seronegative and -seropositive cases (OR, 3.0; 95% CI, 1.8-5.1; OR, 2.3, 95% CI, 0. 8-7.0 respectively). No such association was found for C. pneumoniae. Our prospective study provides sero-epidemiologic evidence that infection with C. trachomatis confers an increased risk for subsequent development of invasive squamous-cell carcinoma of the uterine cervix.


Subject(s)
Adenocarcinoma/epidemiology , Carcinoma, Squamous Cell/epidemiology , Chlamydia Infections/epidemiology , Chlamydia trachomatis/immunology , Uterine Cervical Neoplasms/epidemiology , Uterine Cervical Neoplasms/microbiology , Adenocarcinoma/blood , Adenocarcinoma/microbiology , Antibodies, Bacterial/blood , Carcinoma, Squamous Cell/blood , Carcinoma, Squamous Cell/microbiology , Case-Control Studies , Chlamydia Infections/blood , Chlamydia Infections/complications , Chlamydia Infections/microbiology , Cohort Studies , Female , Finland , Humans , Neoplasm Invasiveness , Norway , Odds Ratio , Prospective Studies , Risk Factors , Seroepidemiologic Studies , Smoking/epidemiology , Sweden , Uterine Cervical Neoplasms/blood
16.
Scand J Gastroenterol ; 34(4): 353-60, 1999 Apr.
Article in English | MEDLINE | ID: mdl-10365894

ABSTRACT

BACKGROUND: Helicobacter pylori infection is an established risk factor for gastric adenocarcinoma. Potential confounding by socioeconomic factors has not been adequately assessed, and the magnitude of the relative risk in relation to gastric subsites, morphologic subtypes, sex, age, and follow-up time need further study. METHODS: We conducted a serologic case-control study nested within the Norwegian JANUS cohort. Between 1972 and 1986 serum was collected from 101,601 subjects who were followed up with regard to cancer development through 1992. RESULTS: Among 208 gastric adenocarcinoma cases, we found a strong positive association between H. pylori infection and non-cardia gastric cancer (odds ratio (OR), 5.15; 95% confidence interval (CI), 2.83-9.37), and a statistically significant negative association with cardia cancer (OR, 0.40; 95% CI, 0.20-0.77). Adjustment for socioeconomic factors and smoking did not materially alter the effect estimates. The association between the infection and non-cardia cancer was stronger for tumors distal to the angulus and tended to be stronger in women than in men. The results were similar across Laurén morphologic subtypes. CONCLUSIONS: These results strengthen the evidence of H. pylori infection as a risk factor in non-cardia gastric cancer. A negative association with H. pylori infection was found for cardia cancer.


Subject(s)
Adenocarcinoma/microbiology , Helicobacter Infections/complications , Helicobacter pylori , Stomach Neoplasms/microbiology , Adenocarcinoma/epidemiology , Cardia , Case-Control Studies , Female , Helicobacter Infections/epidemiology , Humans , Male , Middle Aged , Norway/epidemiology , Risk Factors , Smoking/epidemiology , Socioeconomic Factors , Stomach Neoplasms/epidemiology
17.
Thyroid ; 9(3): 285-8, 1999 Mar.
Article in English | MEDLINE | ID: mdl-10211606

ABSTRACT

In animal models of carcinogenesis, pharmacological doses of dehydroepiandrosterone (DHEA) treatment appear to reduce the incidence of chemically induced thyroid cancers. DHEA and its sulfate (DHEA-S) are secreted in approximately equal amounts, but serum levels of DHEA-S are 300-500 times higher and have no diurnal variation when compared to DHEA. The hypothesis that serum concentrations of DHEA-S may be associated with thyroid cancer risk was tested in a population-based prospective case control study. Data from the practically complete nationwide Cancer Registry of Norway were linked to the data file of a serum bank comprising blood samples from 300,000 Norwegian men and women obtained through national health surveys. A total of 113 donors, who during the years after blood sampling received a diagnosis of thyroid cancer, were identified in the serum bank and were eligible for the study. Each case was matched with 3 controls. Serum levels of DHEA-S were determined blindly. Controls were divided into tertiles, and odds ratios between cases and controls were determined relative to the group with the lowest serum DHEA-S level. The risk of developing thyroid cancer was determined in women 50 years of age or older, in women below age 50, in men, and in the subgroup of 77 cases who had morphologically verified papillary thyroid cancer. No significant association between prediagnostic serum DHEA-S concentrations and thyroid cancer risk was observed. These data indicate that DHEA-S within physiological concentrations does not reduce the risk of thyroid cancer.


Subject(s)
Carcinoma, Papillary/epidemiology , Dehydroepiandrosterone Sulfate/blood , Thyroid Neoplasms/epidemiology , Adult , Age Factors , Carcinoma, Papillary/blood , Case-Control Studies , Female , Humans , Male , Middle Aged , Odds Ratio , Prospective Studies , Risk Assessment , Sex Factors , Thyroid Neoplasms/blood
18.
Int J Cancer ; 80(6): 818-22, 1999 Mar 15.
Article in English | MEDLINE | ID: mdl-10074912

ABSTRACT

Human papillomavirus (HPV) types 16 and 18 are the major risk factors for cervical carcinoma, whereas HPV types 6 and 11 cause benign genital lesions. We wanted to study the joint effect of simultaneous infections with the oncogenic and non-oncogenic HPV types on risk of subsequent development of cervical carcinoma. A cohort of 530,000 women who had donated blood samples to Nordic serum banks between 1973 and 1994 was followed up by linkage to national cancer registries. We identified 182 prospective cases with invasive cervical carcinoma and selected 538 matched controls at random. HPV 6, 11, 16, 18 and 33 seropositivity was used as a marker for the different HPV infections, and seropositivity for Chlamydia trachomatis and cotinine were used as markers for risk-taking sexual behavior and smoking respectively. The adjusted odds ratio (OR) of cervical squamous-cell carcinoma (SCC) was 2.2 for HPV6/11 among HPV16 seronegatives and 5.5 for HPV16 among HPV6/11 seronegatives. Assuming multiplicative joint effect, the expected OR for seropositivity to both HPV6/11 and HPV16 would have been 12, but the observed OR was 1.0. The antagonistic interaction was statistically significant (p = 0.001) and present also under deterministic considerations of possible misclassification bias. Antagonistic interactions were also detected for combinations of HPV16 and HPV18 and of HPV16 and HPV33. The results are in line with the concept that HPV-specific immunity protects against SCC and support primary prevention of SCC by vaccination against the HPVs.


Subject(s)
Antibodies, Viral/blood , Papillomaviridae/pathogenicity , Papillomavirus Infections/epidemiology , Tumor Virus Infections/epidemiology , Uterine Cervical Neoplasms/epidemiology , Adult , Antibodies, Viral/immunology , Blood Donors , Chlamydia Infections/epidemiology , Cohort Studies , Comorbidity , Cross Reactions , Female , Finland/epidemiology , Humans , Norway/epidemiology , Papillomaviridae/classification , Papillomaviridae/immunology , Papillomaviridae/isolation & purification , Papillomavirus Infections/virology , Pregnancy , Pregnancy Complications, Infectious/epidemiology , Pregnancy Complications, Infectious/virology , Prospective Studies , Seroepidemiologic Studies , Sexual Behavior/statistics & numerical data , Smoking/epidemiology , Species Specificity , Sweden/epidemiology , Tumor Virus Infections/virology , Uterine Cervical Neoplasms/virology
19.
J Inherit Metab Dis ; 21(6): 662-70, 1998 Aug.
Article in English | MEDLINE | ID: mdl-9762602

ABSTRACT

Male, identical twins presented with hypotonia, hypoglycaemia, dysmorphic facies, feeding problems, discoloured stools, hepatomegaly, and nephrolithiasis. Elevated blood levels of very long-chain fatty acids and bile acids suggested a peroxisomal disorder. Plasmalogen biosynthesis in cultured fibroblasts was reduced. Morphologically distinct peroxisomes were undetectable in liver. Twin 1 suffered from nephrocalcinosis and severe infection, and died at 18 months of age. Twin 2 was blind and physically severely retarded with epilepsy, but survived up to the age of 5 years. Studies of the fatty acid composition of serum lipids showed barely detectable values of eicosapentaenoic (EPA) and docosahexaenoic acid (DHA). During long-term treatment with these n-3 fatty acids, started at age 10 months, the fatty acid profile of the serum lipids was improved or normalized. Since n-3 fatty acids are essential elements in normal development, notably of the nervous system, we suggest that treatment with EPA and DHA should be started as early as possible in general peroxisomal disorders.


Subject(s)
Diseases in Twins , Fatty Acids, Omega-3/therapeutic use , Fatty Acids/blood , Lipids/blood , Peroxisomal Disorders/metabolism , Fatal Outcome , Humans , Infant , Male , Peroxisomal Disorders/diagnosis , Peroxisomal Disorders/drug therapy , Phospholipids/blood , Twins, Monozygotic
20.
Brain Dev ; 20(4): 227-33, 1998 Jun.
Article in English | MEDLINE | ID: mdl-9661967

ABSTRACT

In this paper the results of an extensive medical investigation of 25 children with childhood autism are presented and compared with those found in a group of non-autistic individuals matched for sex, age and intellectual level, all referred for developmental deviancy of unknown etiology. The examination included a psychiatric assessment and a neurological examination in addition to neurophysiological, chromosomal, metabolic and neuroimaging evaluation. In the clinical examination macrocephaly was found only among the autistic individuals, while the frequency of pathological cerebral CT and clinical parameters such as tendon reflexes and mobility problems was significantly greater in the control group. All the other pathological findings were found to occur with the same frequency in the two groups. Except for research purposes this study did not lend support to those who argue for extensive medical examinations for all children with autism. Based on the present findings, ordinary procedures for assessment of developmentally delayed children should be followed. This should include a systematic clinical neuropaediatric examination, an assessment of vision and hearing and a chromosome study, including that for fragile X.


Subject(s)
Autistic Disorder/physiopathology , Autistic Disorder/psychology , Adolescent , Autistic Disorder/complications , Brain/abnormalities , Central Nervous System Diseases/complications , Child , Child, Preschool , Electroencephalography , Epilepsy/complications , Epilepsy/diagnosis , Female , Humans , Interview, Psychological , Male , Neurologic Examination
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