Risk of breast cancer among female airline cabin attendants. Large European studies are now carried.
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Aircraft↗
Biomedical subjects
M Blettner
Publications and source records attributed to M Blettner.
[Meta-analysis of epidemiologic studies].
BACKGROUND: A metaanalysis is often performed if risk assessment with available epidemiological data is not sensible. The results of these analyses serve mainly to quantify the risk of weak associations. MATERIAL AND METHODS: In this paper we describe methodologic issues of this approach with emphasis on the difference between metaanalysis from published data and from individual patient records. As an example we discuss studies on oral contraceptives and breast cancer. Limits of metaanalysis from published data are given. CONCLUSION: Although metaanalysis with individual data may be cost- and time-consuming their results are more reliable.
Breast Neoplasms↗
Major locus influencing plasma APO-A1 levels also controls plasma HDL3-C concentrations.
Elevated plasma levels of apolipoprotein A1 (APO-A1) and high-density lipoprotein cholesterol (HDL-C) are important protective factors for atherosclerosis and coronary heart disease. Using the data on plasma concentrations of APO-A1, and HDL-C particles HDL2-C and HDL3-C in 970 Israeli individuals belonging to 228 pedigrees, we tested the hypothesis that a major locus influencing interindividual variation in APO-A1 levels also controls interindividual variation in HDL3-C and HDL2-C levels. Univariate and bivariate complex segregation analyses, as implemented in two statistical packages (MAN-3 and PAP-4.0) were applied to test the hypothesis. The results of the analysis clearly indicated the possibility of major gene involvement in the determination of plasma concentration variation of each of the 3 study variables. The results provide strong evidence in support of our hypothesis that HDL3-C genetic variation fully depends on the APO-A1 major locus. In particular, environmental and sporadic models were strongly rejected (P < 0.001) in bivariate analysis. The hypothesis of no pleiotropic effect of the putative APO-A1 locus on HDL3-C transmission was also unequivocally rejected (P < 0.001), while the bivariate Mendelian model was accepted (P > 0.05). The results of bivariate analysis of APO-A1 effect on HDL2-C were not clear. They indicated the possibility of the existence of slight genetic covariation between the two variables, and as yet we were unable to decipher the mode of covariation with the applied models.
Apolipoprotein A-I↗
Identifying influential families using regression diagnostics for generalized estimating equations.
The Generalized Estimating Equations (GEE) is an approach to analyze correlated data. It is applied here to data from an epidemiological study of oesophageal cancer in a high incidence area in China to investigate familial aggregation. Regression diagnostics for mean structures and association structures are used to identify families that influence estimates of these structures. It is shown that most of the families influencing the mean structure have a low age of disease onset in common. Most families identified by regression diagnostics for the association structure influence the parent correlation. It is concluded that regression diagnostic techniques can be used to identify clusters influencing mean and association structures of the models.
China↗
Adult leukaemia: what is the role of currently known risk factors?
Leukaemias are a heterogeneous group of tumours including acute and chronic forms. Considerable efforts have been made to identify risk factors for these diseases, but only a minority of leukaemia cases can currently be attributed to identified or hypothesized factors. This review highlights recent epidemiological literature concerning adult leukaemia, discussing in detail the hereditary, environmental and medical risks. Chromosomal syndromes and genetically based diseases carry a high risk of leukaemia, but rarely occur in the population. Environmental and occupational exposures to chemicals including pesticides have been widely studied, although the results are not consistent, with the exception of benzene. Smoking seems to be a weak causal risk factor. The risk of ionizing radiation has further been quantified in recent studies, although the effects of low doses have not yet been clarified. The results for non-ionizing radiation continue to be inconsistent, but a large effect of electromagnetic fields on the risk of leukaemia appears to be unlikely. Medically applied radio- and chemotherapy are clearly associated with subsequent leukaemia development, and there are links between leukaemia and viral infections. Future research should emphasize the shortcomings in exposure assessment that pervade many studies, and interactions between different risk factors need to be taken into consideration.
Adult↗
Occupational cancer risk in pilots and flight attendants: current epidemiological knowledge.
Occupational studies of aircrew in civil or military aviation did not receive much attention until the beginning of this decade. Since 1990, a number of epidemiological studies has been published on the cancer risk among flight personnel. Their results are equivocal: elevated cancer risks have been observed in some studies, but not in others. The exposure situation for pilots and flight attendants is unique with respect to several factors and particularly in that cosmic rays contribute substantially to their cumulative radiation dose. The average annual doses received are relatively low, however, and commonly range between 3 and 6 mSv. Results of epidemiological studies are presented as well as information on planned studies.
Aviation↗
Serologic response to the E4, E6, and E7 proteins of human papillomavirus type 16 in pregnant women.
OBJECTIVE: In a seroepidemiologic study the effects of pregnancy and other factors on humoral response to human papillomavirus type 16 infection were examined. STUDY DESIGN: Multiple serum samples were taken at 3-month intervals for 15 months from 77 pregnant and 85 nonpregnant women. Serologic response to human papillomavirus type 16 proteins was analyzed with a peptide-based enzyme-linked immunosorbent assay. RESULTS: Seroreactivity was higher in nonpregnant women than in pregnant women, suggesting a reduced humoral immune response against human papillomavirus infections during pregnancy. Among the pregnant women a twofold to threefold decrease in mean reactivity in the E4 protein-based assay was detected between early gestation and delivery. The presence of human papillomavirus type 16 or 18 deoxyribonucleic acid was significantly associated with reactivity to the E6 protein (p = 0.0005) and the E4 protein (p = 0.06). Reactivity to the E4 protein also correlated with an abnormal Papanicolaou smear. CONCLUSIONS: The observation of changes in humoral response to genital human papillomavirus infections during pregnancy warrants further investigation with highly seroreactive assays.
Amino Acid Sequence↗
The effect of oral contraceptive use on the prognosis of node positive breast cancer patients. German Breast Cancer Study Group.
The effect of oral contraceptive (OC) use as a risk factor for breast cancer was recently assessed in a large meta-analysis, but currently available data on the prognostic effect are still insufficient. We investigated the relationship between OC use and standard prognostic factors and the effect of OC use on recurrence-free survival (RFS) and overall survival (OS) in 422 premenopausal pT1a-3aN + M0 patients from two trials of the German Breast Cancer Study Group (GBSG). 137 patients (32.5%) were OC users. They were younger on average (mean age 41.5 years versus 45 years for non-OC users) and the percentage of patients with smaller tumours was higher in the group of OC users. Based on 163 events for RFS and 103 events for OS, no significant effect of OC use on RFS and OS could be demonstrated in univariate and multivariate analyses. In our study of node positive breast cancer cases, OC users were younger and had smaller tumours. This may be an effect of earlier detection of breast cancer, but OC users did not have a better prognosis, both before and after adjustment for tumour size and other prognostic factors.
Adult↗
An international case-control study of adult glioma and meningioma: the role of head trauma.
BACKGROUND: Increased brain tumour risk after head trauma suggested by case reports and clinical series has been previously studied epidemiologically with mixed results. An international multicentre case-control study investigated the role of head trauma from injury or sports participation in adult brain tumour risk. METHODS: In all, 1178 glioma and 330 meningioma cases were individually or frequency matched to 2236 controls. Only exposures that occurred at least 5 years before diagnosis and head injuries that received medical attention were considered. RESULTS: Risk for ever having experienced a head injury was highest for male meningiomas (odds ratio [OR] = 1.5, 95% confidence interval [CI] : 0.9-2.6) but was lower for 'serious' injuries, i.e. those causing loss of consciousness, loss of memory or hospitalization (OR = 1.2, 95% CI: 0.6-2.3). Among male meningiomas, latency of 15 to 24 years significantly increased risk (OR = 5.4, 95% CI: 1.7-16.6), and risk was elevated among those who participated in sports most correlated with head injury (OR = 1.9, 95% CI: 0.7-5.3). Odds ratios were lower for male gliomas (OR = 1.2, 95% CI : 0.9-1.5 for any injury; OR = 1.1, 95% CI: 0.7-1.6 for serious injuries) and in females in general. CONCLUSIONS: Evidence for elevated brain tumour risk after head trauma was strongest for meningiomas in men. Findings related to sports should be interpreted cautiously due to cultural variability in our data and our lack of complete data on physical exercise in general which appeared to be protective.
Adult↗
[Limitations of meta-analysis from published data in epidemiological research].
Metaanalyses of epidemiological studies have increased during the last years and are often used to evaluate the effect of risk factors which are inconsistent in different studies, mainly for small risk factors. Very often a metaanalysis is performed from published data. In this article we discuss this form of a metaanalysis and investigate whether the requirement to get reliable information is achievable with it. We mainly ask questions whether qualitative and quantitative dose-response analysis can be performed. We point out the differences between metaanalysis from experimental data and clinical randomized studies and epidemiological studies. We discuss different arguments that were given for performing metaanalysis in clinical trials and investigate whether they are also valid in observational studies. We mainly concentrate on the problem of estimating a single pooled risk estimate. Two examples from literature are used to show problems with metaanalysis from published data.
Bias↗
Familial aggregation of oesophageal cancer in a high incidence area in China.
BACKGROUND: The high incidence of oesophageal cancer in northern China is attributed predominantly to environmental factors. The role of genetic factors has not been extensively studied. METHODS: Our aim was to study familial aggregation of oesophageal cancer in pedigrees from a defined population base in a high incidence area in China and to quantify the risk associated with different first degree relatives using different analytical approaches. Detailed data on family members of three successive generations and the occurrence of oesophageal and other cancers in family members were collected from a population-based series of 244 oesophageal cancer cases which occurred between 1987 and mid-1992 in Huixian County, Henan. RESULTS: Compared to expected rates, the standardized mortality ratio (SMR) of oesophageal cancer among first degree relatives of oesophageal cancer patients was 2.4 (2.2 in male and 2.7 in female relatives). The corresponding SMR for first and second degree relatives were 1.6 and 2.2. The null hypothesis of 'no familial aggregation' was rejected using Tarone's one-sided score test for binomial distributions indicating some evidence for clustering within families. To account for variance due to between-pairs correlation and family and/or individual specific variables, we fitted a series of regression models using a Generalized Estimation Equations (GEE) approach. The pairwise odds ratios were 2.3 for parent-parent, 1.9 for sib-parent and 1.1 for sib-sib, adjusted for sex, age and sex of index case. DISCUSSION: The existence of familial aggregation of oesophageal cancer in the study population was confirmed using different analyses and a two- to threefold increased risk was found for first degree relatives. The clear association of disease between parent and sib provides some indication of a genetic component. The pairwise association between parents but not between sibs suggests that environmental factors have a stronger action after childhood.
Aged↗
Induced abortion as an independent risk factor for breast cancer.
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Abortion, Induced↗
Controlling for continuous confounders in epidemiologic research.
Multiple regression models are commonly used to control for confounding in epidemiologic research. Parametric regression models, such as multiple logistic regression, are powerful tools to control for multiple covariates provided that the covariate-risk associations are correctly specified. Residual confounding may result, however, from inappropriate specification of the confounder-risk association. In this paper, we illustrate the order of magnitude of residual confounding that may occur with traditional approaches to control for continuous confounders in multiple logistic regression, such as inclusion of a single linear term or categorization of the confounder, under a variety of assumptions on the confounder-risk association. We show that inclusion of the confounder as a single linear term often provides satisfactory control for confounding even in situations in which the model assumptions are clearly violated. In contrast, categorization of the confounder may often lead to serious residual confounding if the number of categories is small. Alternative strategies to control for confounding, such as polynomial regression or linear spline regression, are a useful supplement to the more traditional approaches.
Bias↗
The merits of unrealistic scenarios.
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Computer Simulation↗
Tel Aviv-Heidelberg three-generation offspring study: genetic determinants of plasma fibrinogen level.
Elevated plasma fibrinogen concentrations (fibrinogen) are an important independent risk factor of atherosclerotic disease. Using the kinetic method, we measured fibrinogen in 808 individuals, of which 757 were members of 204 pedigrees. Correlation analysis and two-way analysis of variance (ANOVA) showed a significant association of fibrinogen with age, body mass index (BMI), sex, smoking habits, sport activity, and other lifestyle factors. However, multivariate regression analysis of fibrinogen established an independent significant contribution of only the first three factors. Fibrinogen levels adjusted respectively were subjected to complex segregation analysis. Our aim was to identify the contribution of major gene effects and residual (within the genotype) family correlations on fibrinogen variation. Results of this study suggest codominant alleles at a major locus accounting for 39% of variation. There was also evidence of a significant residual parent/offspring correlation.
Age Factors↗
Sero-epidemiological analysis of the risk of virus infections for childhood leukaemia.
Virus infections have been thought to be involved in the development of childhood leukaemia. In order to address this issue we determined, in a case-control study, the prevalence of antibodies to viruses infecting blood or bone-marrow cells [Epstein-Barr virsus (EBV), human herpes virus type 6 (HHV-6), parvovirus B19] as well as to the human virus known for its tumour-suppressive properties, the adeno-associated virus type 2 (AAV-2), in the sera of 121 children with leukaemia in Germany, and in 197 control individuals, hospitalized for other reasons, and matched for age and gender to the cases. In addition, we developed a questionnaire to be answered by the children's parents, in order to gain information on previous infections of the children as well as to calculate for factors which may influence serological findings. Comparative determination of the prevalence of antibodies against AAV-2, B-19 or HHV-6 revealed no significant differences in cases and controls. However, antibodies to EBV were more frequently found in children with leukaemia younger than 6 years of age (age at the time of diagnosis of leukaemia) than in controls. Apparently, infection with AAV-2 has no protective effect in childhood leukaemia, in contrast to results observed for other malignancies. Similarly, and in accordance with results on leukaemia in adults, we found no indication of a protective effect of infection with the parvovirus B-19. The data suggest that EBV, which is known to be involved in various lymphomas, may play a role in the development of childhood leukaemia in young children.
Adolescent↗
Longitudinal study of the effects of pregnancy and other factors on detection of HPV.
OBJECTIVE: An epidemiologic study of 108 pregnant and 192 non-pregnant women was carried out to determine the effects of pregnancy and other factors on the detection of HPV infection, since both or larger numbers of pregnancies and HPV infection are known to be risk factors for cervical cancer. PATIENTS AND METHODS: Study participants were followed up at 3-months intervals for a period of 15 months (1-6 months after delivery). At each visit, two cervical specimens were taken, one for routine cytology and a second for HPV DNA hybridization using Virapap/Viratype, and a 5-ml blood sample was taken and a self-administered questionnaire was completed. RESULTS: In cervical specimens of the initial examination, HPV DNA was detected among 5.0% of pregnant and 5.2% of nonpregnant women, whereas HPV 16/18 was found in 80% of the HPV-positive specimens. Using multiple cervical specimens taken over time, 13.9% of the pregnant and 15.1% of the nonpregnant women tested positive for HPV DNA at least once. Adjusted for study group, age, and the number of available cervical specimens, ever detection of HPV infection (any type) was associated with more sexual partners and larger numbers of cigarettes smoked daily. An autoregressive generalized linear model was used to analyze the time-dependent multiple observations per study subject. Adjusting for age and trimester of pregnancy, the determinants of detecting high-risk HPV types (16/18 and 31/33/35) in the cervical specimen were an abnormal Pap smear, a positive HPV result in a preceding specimen, more than six sexual partners in the lifetime, and currently smoking more than 20 cigarettes per day with odds ratios of 10.9, 5.6, 3.2, and 2.7, respectively. CONCLUSION: Our data provide no evidence for a higher detection rate of HPV during pregnancy.
Adult↗
Analysis of familial aggregation of atopic eczema and other atopic diseases by ODDS RATIO regression models.
In order to determine the relative importance of genetics and the environment on the occurrence of atopic diseases, we investigated the familial aggregation of atopic eczema, allergic rhinitis, and allergic asthma in the relatives of 426 patients with atopic eczema and 628 subjects with no history of eczema (5,136 family members in total). Analyses were performed by regression models for odds ratios (OR) allowing us to estimate OR for the familial aggregation and simultaneously to adjust for other covariates. Three models were analyzed assuming that the OR i) is the same among any two members of a family, ii) depends on different familial constellations, i.e., whether the pairs are siblings, parents, or parent/sibling pairs, and iii) is not the same between the father and the children and between the mother and the children. The OR of familial aggregation for atopic eczema was 2.16 (95% confidence interval (95%-CI) 1.58-2.96) if no distinction was made between the degree of relationship. Further analyses within the members of the family showed a high OR among siblings (OR = 3.86; 95%-CI 2.10-7.09), while the OR between parents and siblings was only 1.90 (95%-CI 1.31-2.97). Only for atopic eczema was the familial aggregation between fathers and siblings (ms: OR = 2.66; fs: OR = 1.29). This can be explained by stronger maternal heritability, shared physical environment of mother and child, or environmental events that affect the fetus in utero. Since for all atopic diseases a stronger correlation was found between siblings than between siblings and parents, our study indicates that environmental factors, especially during childhood, seem to explain the recently observed increased frequencies of atopic diseases.
Adult↗