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  • 1
    Keywords: SURVIVAL ; CELL ; polymorphism ; ELEMENTS ; susceptibility loci ; GENOME-WIDE ASSOCIATION ; MODIFIERS ; EXPRESSION SIGNATURE ; CHIP-SEQ ; GENETIC INTERACTION NETWORKS
    Abstract: While interplay between BRCA1 and AURKA-RHAMM-TPX2-TUBG1 regulates mammary epithelial polarization, common genetic variation in HMMR (gene product RHAMM) may be associated with risk of breast cancer in BRCA1 mutation carriers. Following on these observations, we further assessed the link between the AURKA-HMMR-TPX2-TUBG1 functional module and risk of breast cancer in BRCA1 or BRCA2 mutation carriers. Forty-one single nucleotide polymorphisms (SNPs) were genotyped in 15,252 BRCA1 and 8,211 BRCA2 mutation carriers and subsequently analyzed using a retrospective likelihood approach. The association of HMMR rs299290 with breast cancer risk in BRCA1 mutation carriers was confirmed: per-allele hazard ratio (HR) = 1.10, 95% confidence interval (CI) 1.04 - 1.15, p = 1.9 x 10-4 (false discovery rate (FDR)-adjusted p = 0.043). Variation in CSTF1, located next to AURKA, was also found to be associated with breast cancer risk in BRCA2 mutation carriers: rs2426618 per-allele HR = 1.10, 95% CI 1.03 - 1.16, p = 0.005 (FDR-adjusted p = 0.045). Assessment of pairwise interactions provided suggestions (FDR-adjusted pinteraction values 〉 0.05) for deviations from the multiplicative model for rs299290 and CSTF1 rs6064391, and rs299290 and TUBG1 rs11649877 in both BRCA1 and BRCA2 mutation carriers. Following these suggestions, the expression of HMMR and AURKA or TUBG1 in sporadic breast tumors was found to potentially interact, influencing patients' survival. Together, the results of this study support the hypothesis of a causative link between altered function of AURKA-HMMR-TPX2-TUBG1 and breast carcinogenesis in BRCA1/2 mutation carriers.
    Type of Publication: Journal article published
    PubMed ID: 25830658
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  • 2
    Keywords: CANCER ; SURVIVAL ; Germany ; INFORMATION ; COHORT ; cohort studies ; cohort study ; DISEASE ; MORTALITY ; POPULATION ; RISK ; HEART ; REDUCTION ; RISK-FACTORS ; ASSOCIATION ; PATTERNS ; HEALTH ; DESIGN ; WOMEN ; MEN ; PROSPECTIVE COHORT ; risk factors ; Jun ; RECRUITMENT ; DIET ; DIETARY ; NETHERLANDS ; European Prospective Investigation into Cancer and Nutrition ; nutrition ; LIFE-STYLE ; HEART-DISEASE ; Mediterranean diet ; REGRESSION ; PATTERN ; INCREASE ; overall survival ; CORONARY-HEART-DISEASE ; INTERVAL ; analysis ; dietary patterns ; elderly ; PRINCIPAL COMPONENTS ; QUALITY INDEX ; ALL-CAUSE MORTALITY ; prospective ; RISK-FACTOR ; VARIABLES ; ENGLAND ; multi-centre cohort study ; BRITISH ADULTS ; coronary heart disease ; FOOD-INTAKE PATTERNS
    Abstract: Objective: To investigate the association of a posteriori dietary patterns with overall survival of older Europeans. Design and setting: This is a multi-centre cohort study. Cox regression analysis was used to investigate the association of the prevailing, a posteriori-derived, plant-based dietary pattern with all-cause mortality in a population of subjects who were 60 years or older at recruitment to the European Prospective Investigation into Cancer and Nutrition (EPIC-Elderly cohort). Analyses controlled for all known potential risk factors. Subjects: in total, 74 607 men and women, 60 years or older at enrolment and without previous coronary heart disease, stroke or cancer, with complete information about dietary intakes and potentially confounding variables, and with known survival status as of December 2003, were included in the analysis. Results: An increase in the score which measures the adherence to the plant-based diet was associated with a lower overall mortality, a one standard deviation increment corresponding to a statistically significant reduction of 14% (95% confidence interval 5-23%). In country-specific analyses the apparent association was stronger in Greece, Spain, Denmark and The Netherlands, and absent in the UK and Germany. Conclusions: Greater adherence to the plant-based diet that was defined a posteriori in this population of European elders is associated with lower all-cause mortality. This dietary score is moderately positively correlated with the Modified Mediterranean Diet Score that has been constructed a priori and was also shown to be beneficial for the Survival of the same EPIC-Elderly cohort
    Type of Publication: Journal article published
    PubMed ID: 17381929
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