METHODS: A case-control study was nested in the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. A total of 2008 incident invasive breast cancer cases (estrogen receptor (ER)+, n = 1622; ER-, n = 386), matched 1:1 to controls, were included in the analysis. Women were predominantly postmenopausal at blood collection (77%); postmenopausal women included users and non-users of postmenopausal hormone therapy (HT). Serum OPG was quantified with an electrochemiluminescence assay. Relative risks (RRs) and 95% confidence intervals (CIs) were calculated using conditional logistic regression.
RESULTS: The associations between OPG and ER+ and ER- breast cancer differed significantly. Higher concentrations of OPG were associated with increased risk of ER- breast cancer (top vs. bottom tertile RR = 1.93 [95% CI 1.24-3.02]; p trend = 0.03). We observed a suggestive inverse association for ER+ disease overall and among women premenopausal at blood collection. Results for ER- disease did not differ by menopausal status at blood collection (p het = 0.97), and we observed no heterogeneity by HT use at blood collection (p het ≥ 0.43) or age at breast cancer diagnosis (p het ≥ 0.30).
CONCLUSIONS: This study provides the first prospective data on OPG and breast cancer risk by hormone receptor subtype. High circulating OPG may represent a novel risk factor for ER- breast cancer.
METHODS: In this study, plasma miRNA profiles from eight early-stage breast cancer patients and nine age-matched (± 2 years) healthy controls were characterized by miRNA array-based approach, followed by differential gene expression analysis, Independent T-test and construction of Receiver Operating Characteristic (ROC) curve to determine the capability of the assays to discriminate between breast cancer and the healthy control.
RESULTS: Based on the 372-miRNAs microarray profiling, a set of 40 differential miRNAs was extracted regarding to the fold change value at 2 and above. We further sub grouped 40 miRNAs of breast cancer patients that were significantly expressed at 2-fold change and higher. In this set, we discovered that 24 miRNAs were significantly upregulated and 16 miRNAs were significantly downregulated in breast cancer patients, as compared to the miRNA expression of healthy subjects. ROC curve analysis revealed that seven miRNAs (miR-125b-5p, miR-142-3p, miR-145-5p, miR-193a-5p, miR-27b-3p, miR-22-5p and miR-423-5p) had area under curve (AUC) value > 0.7 (AUC p-value < 0.05). Overlapping findings from differential gene expression analysis, ROC analysis, and Independent T-Test resulted in three miRNAs (miR-27b-3p, miR-22-5p, miR-145-5p). Cohen's effect size for these three miRNAs was large with d value are more than 0.95.
CONCLUSION: miR-27b-3p, miR-22-5p, miR-145-5p could be potential biomarkers to distinguish breast cancer patients from healthy controls. A validation study for these three miRNAs in an external set of samples is ongoing.
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OBJECTIVE: This study investigated the relationship between adiposity, lifetime physical activities and serum adiponectin as breast cancer risk factors among Malaysian women in Klang Valley, Malaysia.
DESIGN: A case-control study was carried out among 70 newly diagnosed breast cancer patients and 138 controls aged 29 to 65 years old in Klang Valley.
SUBJECTS: The inclusion criteria for both groups were not having menstruation for premenopausal women, no evidence of pregnancy, not lactating and no chronic diseases such as hypertension and diabetes at the time of data collection. In addition, the cases must be pathologically newly diagnosed with breast cancer (stage I to III) and not on any therapy for cancer, with the exception of surgery. The controls were matched with cases for age +/- 5 years and menopausal status.
MEASUREMENTS: Subjects were interviewed to obtain information on socio-demography, health and reproductive history using a pretested questionnaire. Subjects were also asked on their engagement of physical activity since secondary school. Anthropometric parameters included height, weight, waist and hips were also measured. A total of 6 ml of fasting venous blood was drawn for analysis of serum adiponectin in duplicate using Linko Adiponectin ELISA Kit. Fasting blood glucose (FBG) and blood pressure were also measured.
RESULTS: Mean body mass index (BMI) among cases and controls were not significantly different (p> 0.05) at 26.1 -/+ 4.8 kg/m2 and 25.3 -/+ 4.5 kg/m2, respectively. FBG among cases (6.3 -/+ 1.8 mmol/L) was higher than controls (5.6 -/+ 1.1 mmol/L) (p<0.05). Waist hip ratio (WHR) of cases (0.85 -/+ 0.07) was also higher than controls (0.80 -/+ 0.06) (p<0.05). Abdominal obesity (WHR > 0.85) increased risk of breast cancer by three folds [Adjusted OR 3.3 (95%CI 1.8-6.2)] (p<0.05). Adiponectin level was inversely related to waist circumference (r=-0.510, p=0.000), BMI (r=-0.448, p=0.000) and FBG (r=-0.290, p=0.026). Adiponectin level in cases (11.9 -/+ 4.8 microg/ml) were lower than controls (15.2 -/+ 7.3 microg/ml) (p<0.05). A greater reduction of breast cancer risk was observed with the increasing level of serum adiponectin level according to percentiles (p<0.05). Subjects with mean serum adiponectin level at the highest quintile (> 75th)( >or= 16.7 microg/ml) had 80% reduced risk of breast cancer [Adjusted OR 0.2 (0.0-0.6)](p<0.05). A higher percentage of cases (47%) had not engaged in any physical activity throughout life as compared to controls (19%)[Adjusted OR 3.7 (1.7-7.7)](p<0.001).
CONCLUSIONS: Abdominal obesity and physical inactivity throughout life were associated with low serum adiponectin and breast cancer risk among subjects. Thus, it is essential for Malaysian women to be physically active and achieve a healthy waistline in order to increase serum adiponectin level and reduce breast cancer risk.
METHODS: We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects.
RESULTS: We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, ORlog2=1.35 (95% CI 1.04-1.76), Ptrend=0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (Phet=0.98) or baseline HT use (Phet=0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (Ptrend=0.06 vs Ptrend=0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors<4 years compared to ≥4 years after blood donation (Ptrend=0.01 vs Ptrend=0.63; Phet=0.04) and among nulliparous women compared to parous women (Ptrend=0.03 vs Ptrend=0.15; Phet=0.07).
CONCLUSIONS: Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.
MATERIALS AND METHODS: We assessed the association between plasma phospholipid fatty acids and breast cancer risk in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition study. Sixty fatty acids were measured by gas chromatography in pre-diagnostic plasma phospholipids from 2982 incident breast cancer cases matched to 2982 controls. Conditional logistic regression models were used to estimate relative risk of breast cancer by fatty acid level. The false discovery rate (q values) was computed to control for multiple comparisons. Subgroup analyses were carried out by estrogen receptor (ER) and progesterone receptor expression in the tumours.
RESULTS: A high level of palmitoleic acid [odds ratio (OR) for the highest quartile compared with the lowest OR (Q4-Q1) 1.37; 95% confidence interval (CI), 1.14-1.64; P for trend = 0.0001, q value = 0.004] as well as a high desaturation index (DI16) (16:1n-7/16:0) [OR (Q4-Q1), 1.28; 95% C, 1.07-1.54; P for trend = 0.002, q value = 0.037], as biomarkers of de novo lipogenesis, were significantly associated with increased risk of breast cancer. Levels of industrial trans-fatty acids were positively associated with ER-negative tumours [OR for the highest tertile compared with the lowest (T3-T1)=2.01; 95% CI, 1.03-3.90; P for trend = 0.047], whereas no association was found for ER-positive tumours (P-heterogeneity =0.01). No significant association was found between n-3 polyunsaturated fatty acids and breast cancer risk, overall or by hormonal receptor.
CONCLUSION: These findings suggest that increased de novo lipogenesis, acting through increased synthesis of palmitoleic acid, could be a relevant metabolic pathway for breast tumourigenesis. Dietary trans-fatty acids derived from industrial processes may specifically increase ER-negative breast cancer risk.