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Vlaanderen J.,International Agency for Research on Cancer | Taeger D.,Institute for Prevention and Occupational Medicine | Wellman J.,Ruhr University Bochum | Keil U.,University of Munster | And 2 more authors.
Journal of Occupational and Environmental Medicine | Year: 2013

Objective: We extended follow-up of a cohort of German rubber industry workers (active or retired in 1981) by 9 years (1992 to 2000) to reassess previously observed cancer mortality risks. Methods: We calculated standardized mortality ratios and stratified Results by work area, duration of employment, and year of hire. Results: The cohort includes 11,632 men and 1863 women from five tire or general rubber goods producing factories. Among men we observed significantly elevated standardized mortality ratios for cancers of the lung and the pleura in the full cohort and in specific strata. Among women we observed a significantly elevated standardized mortality ratio for cancer of the lung. Conclusions: We observed excess risk for several cancer sites among men and women. Further cancer risk analysis of workers in the rubber industry should focus on differences in work areas and associated exposures. © 2013 Lippincott Williams & Wilkins. Source


Peters S.,University Utrecht | Vermeulen R.,University Utrecht | Olsson A.,International Agency for Research on Cancer | Van Gelder R.,Institute for Occupational Safety and Health | And 16 more authors.
Annals of Occupational Hygiene | Year: 2012

Background: SYNERGY is a large pooled analysis of case-control studies on the joint effects of occupational carcinogens and smoking in the development of lung cancer. A quantitative job-exposure matrix (JEM) will be developed to assign exposures to five major lung carcinogens [asbestos, chromium, nickel, polycyclic aromatic hydrocarbons (PAH), and respirable crystalline silica (RCS)]. We assembled an exposure database, called ExpoSYN, to enable such a quantitative exposure assessment. Methods: Existing exposure databases were identified and European and Canadian research institutes were approached to identify pertinent exposure measurement data. Results of individual air measurements were entered anonymized according to a standardized protocol. Results: The ExpoSYN database currently includes 356551 measurements from 19 countries. In total, 140 666 personal and 215885 stationary data points were available. Measurements were distributed over the five agents as follows: RCS (42%), asbestos (20%), chromium (16%), nickel (15%), and PAH (7%). The measurement data cover the time period from 1951 to present. However, only a small portion of measurements (1.4%) were performed prior to 1975. The major contributing countries for personal measurements were Germany (32%), UK (22%), France (14%), and Norway and Canada (both 11%). Conclusions: ExpoSYN is a unique occupational exposure database with measurements from 18 European countries and Canada covering a time period of >50 years. This database will be used to develop a country-, job-, and time period-specific quantitative JEM. This JEM will enable data-driven quantitative exposure assessment in a multinational pooled analysis of community-based lung cancer case-control studies. © 2011 The Author. Source


Milne R.L.,Genetic and Molecular Epidemiology Group | Milne R.L.,University of Melbourne | Goode E.L.,Mayo Medical School | Garcia-Closas M.,Institute of Cancer Research | And 154 more authors.
Cancer Epidemiology Biomarkers and Prevention | Year: 2011

Background: The single-nucleotide polymorphism (SNP) 5p12-rs10941679 has been found to be associated with risk of breast cancer, particularly estrogen receptor (ER)-positive disease. We aimed to further explore this association overall, and by tumor histopathology, in the Breast Cancer Association Consortium. Methods: Data were combined from 37 studies, including 40,972 invasive cases, 1,398 cases of ductal carcinoma in situ (DCIS), and 46,334 controls, all of white European ancestry, as well as 3,007 invasive cases and 2,337 controls of Asian ancestry. Associations overall and by tumor invasiveness and histopathology were assessed using logistic regression. Results: For white Europeans, the per-allele OR associated with 5p12-rs10941679 was 1.11 (95% CI = 1.08-1.14, P = 7 × 10 -18) for invasive breast cancer and 1.10 (95% CI = 1.01-1.21, P = 0.03) for DCIS. For Asian women, the estimated OR for invasive disease was similar (OR = 1.07, 95%CI = 0.99-1.15, P = 0.09). Further analyses suggested that the association in white Europeans was largely limited to progesterone receptor (PR)- positive disease (per-allele OR = 1.16, 95% CI = 1.12-1.20, P = 1 × 10 -18 vs. OR = 1.03, 95% CI = 0.99-1.07, P = 0.2 for PR-negative disease; P heterogeneity = 2 × 10 -7); heterogeneity by ER status was not observed (P= 0.2) once PR status was accounted for. The association was also stronger for lower grade tumors [per-allele OR (95% CI) = 1.20 (1.14-1.25), 1.13 (1.09-1.16), and 1.04 (0.99-1.08) for grade 1, 2, and 3/4, respectively; Ptrend = 5 × 10 -7]. Conclusion: 5p12 is a breast cancer susceptibility locus for PR-positive, lower grade breast cancer. Impact: Multicenter fine-mapping studies of this region are needed as a first step to identifying the causal variant or variants. ©2011 AACR. Source


Bermejo J.L.,University of Heidelberg | Kabisch M.,German Cancer Research Center | Dunnebier T.,German Cancer Research Center | Schnaidt S.,University of Heidelberg | And 14 more authors.
International Journal of Cancer | Year: 2013

Small ubiquitin-like modifier (SUMO) proteins are covalently attached to target proteins to modify their function. SUMO conjugation participates in processes tightly linked to tumorigenesis. Recently USPL1 (ubiquitin-specific peptidase-like (1) was identified as a SUMO isopeptidase. We report here on the first exploratory study investigating the relationship between genetic variability in USPL1 and breast cancer. Three potentially functional nonsynonymous coding SNPs (rs3742303, rs17609459, rs7984952) were genotyped in 1,021 breast cancer cases and 1,015 controls from the population-based GENICA study. We took advantage of multiple genotype imputation based on HapMap and the 1000 Genomes Project data to refine the association screening in the investigated region. Public genetic databases were also used to investigate the relationship with USPL1 expression in lymphoblastoid cell lines and breast tissue. Women homozygous for the minor C allele of rs7984952 showed a lower risk of Grade 3 breast tumors compared to TT homozygotes (OR 0.50, 95% CI 0.30-0.81). Case-only analyses confirmed the association between rs7984952 and tumor grade (OR 0.60, 95% CI 0.39-0.93). Imputation results in a 238 kb region around rs7984952 based on HapMap and the 1000 Genomes Project data were similar. No imputed variant showed an association signal stronger than rs7984952. USPL1 expression in tumor breast tissue increased with the number of C alleles. The present study illustrates the contribution of multiple imputation of genotypes using public data repositories to standard genotyping laboratory. The provided information may facilitate the design of independent studies to validate the association between USPL1 rs7984952 and risk of Grade 3 breast tumors. Copyright © 2013 UICC. Source


Stevens K.N.,Mayo Medical School | Vachon C.M.,Mayo Medical School | Lee A.M.,Mayo Medical School | Slager S.,Mayo Medical School | And 86 more authors.
Cancer Research | Year: 2011

Triple-negative breast cancers are an aggressive subtype of breast cancer with poor survival, but there remains little known about the etiologic factors that promote its initiation and development. Commonly inherited breast cancer risk factors identified through genome-wide association studies display heterogeneity of effect among breast cancer subtypes as defined by the status of estrogen and progesterone receptors. In the Triple Negative Breast Cancer Consortium (TNBCC), 22 common breast cancer susceptibility variants were investigated in 2,980 Caucasian women with triple-negative breast cancer and 4,978 healthy controls. We identified six singlenucleotide polymorphisms, including rs2046210 (ESR1), rs12662670 (ESR1), rs3803662 (TOX3), rs999737 (RAD51L1), rs8170 (19p13.1), and rs8100241 (19p13.1), significantly associated with the risk of triple-negative breast cancer. Together, our results provide convincing evidence of genetic susceptibility for triple-negative breast cancer. ©2011 AACR. Source

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