METHODS: We used pooled data on tumor markers (estrogen and progesterone receptor, human epidermal growth factor receptor-2 (HER2)) and reproductive risk factors (parity, age at first full-time pregnancy (FFTP) and age at menarche) from 28,095 patients with invasive BC from 34 studies participating in the Breast Cancer Association Consortium (BCAC). In a case-only analysis, we used logistic regression to assess associations between reproductive factors and BC subtype compared to luminal A tumors as a reference. The interaction between age and parity in BC subtype risk was also tested, across all ages and, because age was modeled non-linearly, specifically at ages 35, 55 and 75 years.
RESULTS: Parous women were more likely to be diagnosed with triple negative BC (TNBC) than with luminal A BC, irrespective of age (OR for parity = 1.38, 95% CI 1.16-1.65, p = 0.0004; p for interaction with age = 0.076). Parous women were also more likely to be diagnosed with luminal and non-luminal HER2-like BCs and this effect was slightly more pronounced at an early age (p for interaction with age = 0.037 and 0.030, respectively). For instance, women diagnosed at age 35 were 1.48 (CI 1.01-2.16) more likely to have luminal HER2-like BC than luminal A BC, while this association was not significant at age 75 (OR = 0.72, CI 0.45-1.14). While age at menarche was not significantly associated with BC subtype, increasing age at FFTP was non-linearly associated with TNBC relative to luminal A BC. An age at FFTP of 25 versus 20 years lowered the risk for TNBC (OR = 0.78, CI 0.70-0.88, p
METHODS: Germ line DNA from a hospital-based study of 2575 unselected patients with breast cancer and 2809 healthy controls were subjected to amplicon-based targeted sequencing of exonic and proximal splice site junction regions of BRCA1 and BRCA2 using the Fluidigm Access Array system, with sequencing conducted on a Illumina HiSeq2500 platform. Variant calling was performed with GATK UnifiedGenotyper and were validated by Sanger sequencing.
RESULTS: Fifty-five (2.1%) BRCA1 and 66 (2.6%) BRCA2 deleterious mutations were identified among patients with breast cancer and five (0.18%) BRCA1 and six (0.21%) BRCA2 mutations among controls. One thousand one hundred and eighty-six (46%) patients and 97 (80%) carriers fulfilled the National Comprehensive Cancer Network guidelines for genetic testing.
CONCLUSION: Five per cent of unselected Asian patients with breast cancer carry deleterious variants in BRCA1 or BRCA2. While current referral guidelines identified the majority of carriers, one in two patients would be referred for genetic services. Given that such services are largely unavailable in majority of low-resource settings in Asia, our study highlights the need for more efficient guidelines to identify at-risk individuals in Asia.
METHODS: Volumetric mammographic density was compared for 1501 Malaysian and 4501 Swedish healthy women, matched on age and body mass index. We used multivariable log-linear regression to determine the risk factors associated with mammographic density and mediation analysis to identify factors that account for differences in mammographic density between the two cohorts.
RESULTS: Compared to Caucasian women, percent density was 2.0% higher among Asian women (p breast cancer may be accounted for by height, weight, and parity. Given that pre-menopausal Asian and Caucasian women have similar population risk to breast cancer but different dense volume, development of more appropriate biomarkers of risk in pre-menopausal women is required.
METHODS: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2.
RESULTS: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10-6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance.
CONCLUSION: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
OBJECTIVE: To assess the association of premenopausal and postmenopausal breast cancer risk with fat and fat subtypes intake.
METHODOLOGY: This is a population based case-control study conducted in Kuala Lumpur, Malaysia from January 2006 to December 2007. Food intake pattern was collected from 382 breast cancer patients and 382 control group via an interviewer-administered food frequency questionnaire. Logistic regression was used to compute odds ratios (OR) with 95% confidence intervals (CI) and a broad range of potential confounders was included in analysis.
RESULTS: This study showed that both premenopausal and postmenopausal breast cancer risk did not increase significantly with greater intake of total fat [quartile (Q) 4 versus Q1 OR=0.76, 95% CI, 0.23-2.45 and OR=1.36, 95% CI, 0.30-3.12], saturated fat (ORQ4 to Q1=1.43, 95% CI, 0.51-3.98 and ORQ4 to Q1=1.75, 95% CI, 0.62-3.40), monounsaturated fat (ORQ4 to Q1=0.96, 95% CI, 0.34-1.72 and ORQ4 to Q1=1.74, 95% CI, 0.22-2.79), polyunsaturated fat (ORQ4 to Q1=0.64, 95% CI, 0.23-1.73 and ORQ4 to Q1=0.74, 95% CI, 0.39-1.81), n-3 polyunsaturated fat (ORQ4 to Q1=1.10, 95% CI, 0.49-2.48 and ORQ4 to Q1=0.78, 95% CI, 0.28-2.18), n-6 polyunsaturated fat (ORQ4 to Q1=0.67, 95% CI, 0.24-1.84 and ORQ4 to Q1=0.71, 95% CI, 0.29-1.04) or energy intake (ORQ4 to Q1=1.52, 95% CI, 0.68-3.38 and ORQ4 to Q1=2.21, 95% CI, 0.93-3.36).
CONCLUSION: Total fat and fat subtypes were not associated with pre- and postmenopausal breast cancer risk after controlling for age, other breast cancer risk factors and energy intake. Despite the lack of association, the effects of total fat and fat subtypes intake during premenopausal years towards postmenopausal breast cancer risk still warrant investigation.
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.