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    Keywords: CANCER ; MODEL ; MODELS ; DIAGNOSIS ; COHORT ; cohort studies ; cohort study ; HISTORY ; PROTEIN ; radiation ; PATIENT ; MARKER ; treatment ; ASSOCIATION ; BREAST ; breast cancer ; BREAST-CANCER ; HEALTH ; HUMANS ; AGE ; WOMEN ; PROSPECTIVE COHORT ; smoking ; chemotherapy ; MARKERS ; CANCER-PATIENTS ; C-REACTIVE PROTEIN ; FAILURE ; CANCER PATIENTS ; inflammation ; physical activity ; SERUM ; ADULT ; REGRESSION ; PROGNOSTIC-FACTOR ; PHYSICAL-ACTIVITY ; SURVIVORS ; heart failure ; methods ; CLINICAL CHARACTERISTICS ; prospective ; female ; multivariate analysis ; BMI ; population-based ; cross-sectional studies ; Aged ; Middle Aged ; WAIST CIRCUMFERENCE ; Aged,80 and over ; VITAMIN ; C-REACTIVE-PROTEIN ; C-Reactive Protein/*analysis ; Breast Neoplasms/*blood/*epidemiology/ethnology ; Life Style ; Serum Amyloid A Protein/*analysis ; Tumor Markers,Biological/*blood
    Abstract: INTRODUCTION: Inflammatory status may be an important prognostic factor for breast cancer. Correlates of markers of inflammation in breast cancer survivors have not been thoroughly evaluated. METHODS: Using data from, the Health, Eating, Activity, and Lifestyle (HEAL) Study (a population-based, multiethnic prospective cohort study of female breast cancer patients) we evaluated the associations between circulating markers of inflammation (C-reactive protein [CRP] and serum amyloid A [SAA], measured approximately 31 months after diagnosis) and several demographic, lifestyle, and clinical characteristics in 741 disease-free breast cancer survivors. Analysis of variance and regression methods were used for statistical analyses of log-transformed values of CRP and SAA. RESULTS: After adjusting for age, BMI, ethnicity, and study site, higher concentrations of CRP were associated with increasing concentration of SAA (P-trend 〈 0.0001), increasing age (P-trend 〈 0.0001), increasing BMI (P-trend 〈 0.0001), increasing waist circumference (P-trend 〈 0.0001), positive history of heart failure (P = 0.0007), decreasing physical activity (P-trend = 0.005), Hispanic ethnicity (P = 0.05 vs. non-Hispanic white), and current smoking (P = 0.03 vs. never smoking). Vitamin E supplementation (P = 0.0005), tamoxifen use (P = 0.008), and radiation treatment (compared to no chemotherapy or radiation; P = 0.04) were associated with reduced CRP. Associations of CRP with clinical characteristics were not significant in the adjusted models. In a multivariate analysis, CRP showed significant associations with waist circumference, BMI, age, history of heart failure, tamoxifen use, and vitamin E supplementation (R (2) = 0.35). Similar, yet fewer, associations were observed for SAA (R (2) = 0.19). CONCLUSIONS: This study highlights important correlates of inflammatory status in breast cancer patients. Our results are consistent with those from similar studies of healthy women.
    Type of Publication: Journal article published
    PubMed ID: 18401703
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    Keywords: POPULATION ; RISK-FACTORS ; OVARIAN-CANCER ; susceptibility loci ; CHINESE WOMEN ; AFRICAN-AMERICAN ; FGFR2 ; CONFER SUSCEPTIBILITY ; FAMILY REGISTRY ; WHOLE-GENOME
    Abstract: Early-onset breast cancer (EOBC) causes substantial loss of life and productivity, creating a major burden among women worldwide. We analyzed 1,265,548 Hapmap3 single-nucleotide polymorphisms (SNP) among a discovery set of 3,523 EOBC incident cases and 2,702 population control women ages 〈= 51 years. The SNPs with smallest P values were examined in a replication set of 3,470EOBC cases and 5,475 control women. We also tested EOBC association with 19,684 genes by annotating each gene with putative functional SNPs, and then combining their P values to obtain a gene-based P value. We examined the gene with smallest P value for replication in 1,145 breast cancer cases and 1,142 control women. The combined discovery and replication sets identified 72 new SNPs associated with EOBC(P 〈 4 x 10(-8)) located in six genomic regions previously reported to contain SNPs associated largely with later-onset breast cancer (LOBC). SNP rs2229882 and 10 other SNPs on chromosome 5q11.2 remained associated (P 〈 6 x 10(-4)) after adjustment for the strongest published SNPs in the region. Thirty-two of the 82 currently known LOBC SNPs were associated with EOBC (P 〈 0.05). Low power is likely responsible for the remaining 50 unassociated known LOBC SNPs. The gene-based analysis identified an association between breast cancer and the phosphofructokinase-muscle (PFKM) gene on chromosome 12q13.11 that met the genome-wide gene-based threshold of 2.5 x 10(-6). In conclusion, EOBC and LOBC seem to have similar genetic etiologies; the 5q11.2 region may contain multiple distinct breast cancer loci; and the PFKM gene region is worthy of further investigation. These findings should enhance our understanding of the etiology of breast cancer.
    Type of Publication: Journal article published
    PubMed ID: 24493630
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    Keywords: CANCER ; SURVIVAL ; tumor ; MODEL ; MODELS ; DIAGNOSIS ; FOLLOW-UP ; COHORT ; cohort studies ; cohort study ; DEATH ; DISEASE ; HISTORY ; LONG-TERM ; PROTEIN ; PATIENT ; MARKER ; INDEX ; BIOMARKERS ; ASSOCIATION ; BREAST ; breast cancer ; BREAST-CANCER ; STAGE ; PROGRESSION ; HEALTH ; HUMANS ; AGE ; WOMEN ; PROSPECTIVE COHORT ; MARKERS ; LONG-TERM SURVIVAL ; DOSE-RESPONSE ; CANCER-PATIENTS ; C-REACTIVE PROTEIN ; RISK ASSESSMENT ; PREDICTORS ; CANCER PATIENTS ; inflammation ; SERUM ; ADULT ; CARDIOVASCULAR-DISEASE ; development ; biomarker ; methods ; PROGNOSTIC MARKER ; EVENTS ; prospective ; female ; Middle Aged ; cancer survival ; Proportional Hazards Models ; LOW-GRADE ; hazard ratio ; treatment outcome ; C-REACTIVE-PROTEIN ; Disease-Free Survival ; *Prognosis ; Biological Markers/*blood ; Breast Neoplasms/blood/diagnosis/*mortality/pathology ; C-Reactive Protein/*metabolism ; Inflammation/blood/etiology/mortality ; Serum Amyloid A Protein/*metabolism ; Young Adult
    Abstract: PURPOSE Chronic inflammation is believed to contribute to the development and progression of breast cancer. Systemic C-reactive protein (CRP) and serum amyloid A (SAA) are measures of low-grade chronic inflammation and potential predictors of cancer survival. PATIENTS AND METHODS We evaluated the relationship between circulating markers of inflammation and breast cancer survival using data from the Health, Eating, Activity, and Lifestyle (HEAL) Study (a multiethnic prospective cohort study of women diagnosed with stage 0 to IIIA breast cancer). Circulating concentrations of CRP and SAA were measured approximately 31 months after diagnosis and tested for associations with disease-free survival (approximately 4.1 years of follow-up) and overall survival (approximately 6.9 years of follow-up) in 734 disease-free breast cancer survivors. Cox proportional hazards models were used with adjustment for potential confounding factors to generate hazard ratios (HRs) and 95% CIs. Results Elevated SAA and CRP were associated with reduced overall survival, regardless of adjustment for age, tumor stage, race, and body mass index (SAA P trend 〈 .0001; CRP P trend = .002). The HRs for SAA and CRP tertiles suggested a threshold effect on survival, rather than a dose-response relationship (highest v lowest tertile: SAA HR = 3.15; 95% CI, 1.73 to 5.65; CRP HR = 2.27; 95% CI, 1.27 to 4.08). Associations were similar and still significant after adjusting for self-reported history of cardiovascular events and censoring cardiovascular disease deaths. Elevated CRP and SAA were also associated with reduced disease-free survival, although these associations were of borderline significance (SAA P trend = .04; CRP P trend = .07). CONCLUSION Circulating SAA and CRP may be important prognostic markers for long-term survival in breast cancer patients, independent of race, tumor stage, and body mass index.
    Type of Publication: Journal article published
    PubMed ID: 19470939
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