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  • 1
    Electronic Resource
    Electronic Resource
    Low-penetrance susceptibility to breast cancer due to CHEK2 * 1100delC in noncarriers of BRCA1 or BRCA2 mutations (2002)
    [s.l.] : Nature Publishing Group
    Nature genetics 31 (2002), S. 55-59 
    Details
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Mutations in BRCA1 and BRCA2 confer a high risk of breast and ovarian cancer, but account for only a small fraction of breast cancer susceptibility. To find additional genes conferring susceptibility to breast cancer, we analyzed CHEK2 (also known as CHK2), which encodes a cell-cycle checkpoint ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/ng879
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  • 2
    Electronic Resource
    Electronic Resource
    A common variant in BRCA2 is associated with both breast cancer risk and prenatal viability (2000)
    [s.l.] : Nature America Inc.
    Nature genetics 26 (2000), S. 362-364 
    Details
    ISSN: 1546-1718
    Source: Nature Archives 1869 - 2009
    Topics: Biology , Medicine
    Notes: [Auszug] Inherited mutations in the gene BRCA2 predispose carriers to early onset breast cancer, but such mutations account for fewer than 2% of all cases in East Anglia. It is likely that low penetrance alleles explain the greater part of inherited susceptibility to breast cancer; polymorphic variants in ...
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1038/81691
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  • 3
    Electronic Resource
    Electronic Resource
    Breast cancer risk assessment: use of complete pedigree information and the effect of misspecified ages at diagnosis of affected relatives (1998)
    Springer
    Human genetics 〈Berlin〉 102 (1998), S. 348-356 
    Details
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004390050704
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  • 4
    Electronic Resource
    Electronic Resource
    A high proportion of mutations in the BRCA1 gene in German breast/ovarian cancer families with clustering of mutations in the 3′ third of the gene (1998)
    Springer
    Human genetics 〈Berlin〉 103 (1998), S. 154-161 
    Details
    ISSN: 1432-1203
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology , Medicine
    Notes: Abstract We have analyzed 61 German breast and breast/ovarian cancer families for BRCA1 mutations using single-strand conformation polymorphism analysis (SSCP) followed by sequencing. Forty-seven of the families had at least three cases (at least two under 60 years) and 14 families had only two cases of breast/ovarian cancer (at least one under 50 years). Twenty-eight families were breast/ovarian and 33 were breast cancer-only families. Eighteen mutations in BRCA1 were detected in 11/28 breast/ovarian cancer families and 7/33 breast cancer families and none in the families with only two cases. We identified 17 truncation mutations (8 frameshift, 7 nonsense and 2 splice variants) and one missense mutation. Seven of these are novel and two, the 5382insC and 5622C→T mutations, occurred in two apparently unrelated families. The genotype of the two families with the 5382insC mutation is compatible with the rare haplotype segregating with the 5382insC mutation in different populations, further supporting its European origin. One unclassified missense alteration, R841W, was found in one family but did not segregate with the disease, suggesting that it is more likely a polymorphism. We also report and discuss the sequence of several new unclassified single-nucleotide changes first identified by SSCP. Of the 18 mutations, 13 occurred in the 3′ third of the gene (end of exon 11–24) and ovarian cancers were found in eight of these families.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/s004390050799
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  • 5
    Electronic Resource
    Electronic Resource
    Modifying effect of reproductive risk factors on the age at onset of breast cancer for German BRCA1 mutation carriers (1997)
    Springer
    Journal of cancer research and clinical oncology 123 (1997), S. 272-279 
    Details
    ISSN: 1432-1335
    Keywords: Key words Breast cancer  ;  Genetic susceptibility  ;  Modifying factors  ;  Survival analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Female carriers of mutations in the BRCA1 gene on chromosome 17q have a very high risk of developing breast and/or ovarian cancer during their lifetime. There is, however, little knowledge of to what extent non-genetic risk factors, such as age at menarche, age at first birth, and body mass index, alter the age at onset of disease. We identified individuals showing a high probability of linkage to BRCA1 and examined the effect of other known risk factors on disease risk. A total of 43 families with at least three breast or ovarian cancer cases, including two affected before 60 years of age, were studied for linkage to the susceptibility locus BRCA1. Blood samples from relevant family members were used to genotype for at least three chromosome 17q polymorphic markers. Information on reproductive history, hormone use and lifestyle factors was collected from female members using a self-administered questionnaire. Diagnoses of breast and ovarian cancer were verified through pathology reports and paraffin blocks were obtained when available. Multipoint LOD (logarithm of the odds) scores were calculated and individuals from 10 families with a posteriori probability for linkage greater than 0.90 were used for further analysis. Forty-six BRCA1 carriers were identified by the disease haplotype; 30 were affected with breast cancer and 5 with ovarian cancer. Proportional- hazards analysis of age at onset of breast cancer yielded increased relative risks of 1.74 for early age at menarche (〈14 years), 1.58 for late age at first birth ( ≥ 25 years) or nulliparity, and 2.78 for recent year of birth ( ≥ 1940); however, none of the risk estimates was statistically significant. When both breast and ovarian cancer were considered as disease endpoints, the birth cohort effect was stronger and age at first birth showed no effect. Our data provide some evidence that reproductive risk factors for breast cancer have an effect on age at onset for BRCA1 carriers. However, considering that our analyses were based on limited numbers, these results warrant further clarification.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01208638
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  • 6
    Electronic Resource
    Electronic Resource
    Modifying effect of reproductive risk factors on the age at onset of breast cancer for GermanBRCA1 mutation carriers (1997)
    Springer
    Journal of cancer research and clinical oncology 123 (1997), S. 272-279 
    Details
    ISSN: 1432-1335
    Keywords: Breast cancer ; Genetic susceptibility ; Modifying factors ; Survival analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Female carriers of mutations in theBRCA1 gene on chromosome 17q have a very high risk of developing breast and/or ovarian cancer during their life-time. There is, however, little knowledge of to what extent non-genetic risk factors, such as age at menarche, age at first birth, and body mass index, alter the age at onset of disease. We identified individuals showing a high probability of linkage toBRCA1 and examined the effect of other known risk factors on disease risk. A total of 43 families with at least three breast or ovarian cancer cases, including two affected before 60 years of age, were studied for linkage to the susceptibility locusBRCA1. Blood samples from relevant family members were used to genotype for at least three chromosome 17q polymorphic markers. Information on reproductive history, hormone use and lifestyle factors was collected from female members using a self-administered questionnaire. Diagnoses of breast and ovarian cancer were verified through pathology reports and paraffin blocks were obtained when available. Multipoint LOD (logarithm of the odds) scores were calculated and individuals from 10 families with a posteriori probability for linkage greater than 0.90 were used for further analysis. Forty-sixBRCA1 carriers were identified by the disease haplotype; 30 were affected with breast cancer and 5 with ovarian cancer. Proportional-hazards analysis of age at onset of breast cancer yielded increased relative risks of 1.74 for early age at menarche (〈14 years), 1.58 for late age at first birth (≥25 years) or nulliparity, and 2.78 for recent year of birth (≥1940); however, none of the risk estimates was statistically significant. When both breast and ovarian cancer were considered as disease endpoints, the birth cohort effect was stronger and age at first birth showed no effect. Our data provide some evidence that reproductive risk factors for breast cancer have an effect on age at onset forBRCA1 carriers. However, considering that our analyses were based on limited numbers, these results warrant further clarification.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01208638
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  • 7
    Electronic Resource
    Electronic Resource
    Lung cancer mortality among European rock/slag wool workers: exposure-response analysis (1998)
    Springer
    Cancer causes & control 9 (1998), S. 411-416 
    Details
    ISSN: 1573-7225
    Keywords: Europe ; dose-response ; lung cancer ; man-made vitreous fibers ; men ; occupation
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Objectives: The purpose was to analyze the relationship between semi-quantitative indices of exposure to man-made vitreous fibers and lung cancer mortality among European rock/slag wool (RSW) workers. Methods: The study population comprised 9,603 male workers employed in RSW production in seven factories in Denmark, Norway, Sweden, and Germany, followed up for mortality as of 1990-91. Estimates of past exposure to respirable fibers were used to calculate cumulative exposure with a 15-year lag and maximum annual exposure based on employment history up to 1977. Rate ratios were estimated via multivariate Poisson regression, adjusting for country, age, calendar year, time since first employment, and employment status. Results: A total of 159 lung cancer deaths were included in the analysis of which 97 among workers with more than one year of employment. We found nonstatistically significant trends in lung cancer risk according to cumulative exposure. Relative risks (RR) in the four quartiles were 1.0 (reference), 1.3 (95 percent confidence interval [CI]=0.8-2.4), 1.2 (CI=0.7-2.1), and 1.5 (CI=0.7-3.0, P test for trend=0.4). When workers with less than one year of employment were excluded, there was no increased risk; the RRs in the four quartiles were 1.0, 0.9 (CI=0.4-2.0), 0.8 (CI=0.3-1.9), and 1.0 (CI=0.4-2.7). No trend was present according to maximum annual exposure. The results were not consistent among countries. Conclusions: We found a positive association between exposure to respirable fibers and lung cancer mortality. However, the lack of statistical significance, the dependence of the results on inclusion of short-term workers, the lack of consistency among countries, and the possible correlation between exposure to respirable fibers and to other agents reduce the weight of such evidence.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008871718323
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  • 8
    Electronic Resource
    Electronic Resource
    Familial risk and genetic susceptibility for breast cancer (1994)
    Springer
    Cancer causes & control 5 (1994), S. 458-470 
    Details
    ISSN: 1573-7225
    Keywords: Breast neoplasms ; case-control studies ; familial risk ; genetics ; pedigree analysis
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Clinical observations suggest that breast cancer is occasionallyinherited as an autosomal dominant disease in families. Epidemiologic studies consistently have shown that a history of breast cancer in a first-degree relative increases a woman's risk of breast cancer when compared with the general population. The risk is similar if a mother or sister is affected and is increased further if both are affected. The difficulty with such an observation is that in itself it does not clarify the nature of the true underlying risk factors which could be genetic or due to the aggregation of environmental risk factors in families. Complex segregation analysis of breast cancer aggregation in families suggests that breast cancer susceptibility is due to an autosomal dominant inheritance of one or more rare genes in a few families in which carriers have a high probability of developing the disease perhaps as great as 100 percent. Close linkage of a breast-cancer-susceptibility gene (BRCA1), between markers of the chromosomal region 17q12-q21 on the long arm of chromosome 17, with breast cancer recently has been reported. Families linked to BRCA1 were more likely to have early onset of breast cancer or have breast and ovarian cancer in the family. It is likely that other genes play a role in the unlinked breastcancer families. Both the epidemiologic and genetic data suggest that breast cancer is a heterogeneous disease.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1007/BF01694760
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  • 9
    Electronic Resource
    Electronic Resource
    Breastfeeding and breast cancer risk by age 50 among women in Germany (2000)
    Springer
    Cancer causes & control 11 (2000), S. 687-695 
    Details
    ISSN: 1573-7225
    Keywords: breast neoplasms ; breastfeeding ; family history ; Germany ; population-based case–control study
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Epidemiological evidence which suggests that prolonged breastfeeding protects against breast cancer has accumulated in recent years. Issues with regard to the timing of breastfeeding and effect modification by correlates of breastfeeding and other risk factors of breast cancer remain unresolved. Methods: A population-based case–control family study of breast cancer among women diagnosed by the age of 50, conducted in two geographic areas in Germany, was used to evaluate the effect of breastfeeding on risk of breast cancer. Results: Among parous women in this study (553 cases, 1094 age-matched population controls), having ever breastfed a child for at least 1 month did not confer protection (odds ratio of 0.9 and 95% confidence interval (CI) 0.8–1.2). However, risk of breast cancer significantly decreased with increasing duration of breastfeeding (p for trend = 0.01) and the estimated relative risk was 0.6 (95% CI 0.4–0.9) for 13–24 months of cumulative breastfeeding and 0.5 (95% CI 0.3–1.1) for 25 months or more. Risk was less related to number of children breastfed than to increasing average length of breastfeeding per child (p for trend = 0.03). Conclusions: The reduction in risk associated with duration of breastfeeding was not primarily due to breastfeeding the firstborn and more evident in women who were older ( 〉 25 years) when they first breastfed and among women who experienced a recent full-term pregnancy. Risks were modified somewhat by a first-degree family history of breast cancer whereby a greater reduction in risk per additional month of breastfeeding was observed among women with a family history than those without (0.9 vs. 1.0). The study results support a protective role of prolonged breastfeeding against the development of breast cancer in predominantly premenopausal women in Germany.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1008907901087
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  • 10
    Electronic Resource
    Electronic Resource
    Coffee consumption and bladder cancer in nonsmokers: a pooled analysis of case–control studies in European countries (2000)
    Springer
    Cancer causes & control 11 (2000), S. 925-931 
    Details
    ISSN: 1573-7225
    Keywords: bladder cancer ; coffee consumption ; nonsmokers
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Background: Coffee consumption has been associated with an excess bladder cancer risk, but results from epidemiological studies are inconsistent. This association has been long debated, in part due to the potential confounding by smoking. We examined the risk associated with coffee consumption in nonsmokers in a pooled analysis of ten European bladder cancer case–control studies. Methods: The pooled data set comprises 564 cases and 2929 hospital or population controls who had never smoked. They were enrolled in ten studies conducted in Denmark, Germany, Greece, France, Italy and Spain. Information on coffee consumption and occupation was re-coded following standard criteria. Unconditional logistic regression was applied adjusting for age, study center, occupation and gender. Results: Seventy-nine percent of the study population reported having drunk coffee, and 2.4% were heavy drinkers, reporting having drunk on average ten or more cups per day. There was no excess risk in ever coffee drinkers (OR = 1.0, 95% CI 0.8–1.3) compared to never drinkers. The risk did not increase monotonically with dose but a statistically significant excess risk was seen for subjects having drunk ten or more cups per day (OR = 1.8, 95% CI 1.0–3.3). This excess was seen in both men and women. There was no evidence of an association of the risk with duration or type of coffee consumption. The pooled results were not dependent on the findings of any specific study, but they depended on the type of controls with an overall excess risk observed only for studies using hospital controls. Conclusion: Nonsmokers who are heavy coffee drinkers may have a small excess risk of bladder cancer. Although these results cannot be attributed to confounding by smoking, the possibility of bias in control selection cannot be discarded. On the basis of these results, only a very small proportion of cancers of the bladder among nonsmokers could be attributed to coffee drinking.
    Type of Medium: Electronic Resource
    URL: http://dx.doi.org/10.1023/A:1026524014954
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