Angiogenesis genes, dietary oxidative balance and breast cancer risk and progression: The breast cancer health disparities study

Abstract

Angiogenesis is essential for tumor development and progression. Genetic variation in angiogenesis-related genes may influence breast carcinogenesis. We evaluated dietary factors associated with oxidative balance, DDIT4 (1 SNP), FLT1 (35 SNPs), HIF1A (4 SNPs), KDR (19 SNPs), MPO (1 SNP), NOS2A (15 SNPs), TEK (40 SNPs), and VEGFA (8 SNPs) and breast cancer risk among Hispanic (2111 cases, 2597 controls) and non-Hispanic white (NHW) (1481 cases, 1586 controls) women in the Breast Cancer Health Disparities Study. Adaptive Rank Truncated Product (ARTP) analysis was used to determine gene and pathway significance with breast cancer. TEK was associated with breast cancer overall (PARTP = 0.03) and with breast cancer survival (PARTP = 0.01). KDR was of borderline significance overall (PARTP = 0.07), although significantly associated with breast cancer in both low and intermediate Native American (NA) ancestry groups (PARTP = 0.02) and ER+/PR- tumor phenotype (PARTP = 0.008). Both VEGFA and NOS2A were associated with ER−/PR− tumor phenotype (PARTP = 0.01 and PARTP = 0.04 respectively). FLT1 was associated with breast cancer survival among those with low NA ancestry (PARTP = 0.009). With respect to diet, having a higher dietary oxidative balance score (DOBS) was significantly associated with lower breast cancer risk (OR 0.74 95% CI 0.64–0.84), with the strongest associations observed for women with the highest NA ancestry (OR 0.44 95 %CI 0.30–0.65). We observed few interactions between DOBS and angiogenesis-related genes. Our data suggest that dietary factors and genetic variation in angiogenesis-related genes contribute to breast cancer carcinogenesis.

Genetic variation in the JAK/STAT/SOCS signaling pathway influences breast cancer-specific mortality through interaction with cigarette smoking and use of aspirin/NSAIDs: the Breast Cancer Health Disparities Study

“…Regular cigarette smoking was evaluated as current, former, or never, where regular was defined as having smoked one or more cigarettes for six months or longer in 4-CBCS and SFBCS (data available for a subset of subjects only) or having smoked 100 or more cigarettes in MCBCS. A dietary oxidative balance score (DOBS) that included nutrients with anti- or pro-oxidative properties was used [20]. Dietary information was collected via a computerized validated diet history questionnaire in 4-CBCS [12, 21], a 104-item semi-quantitative Food Frequency Questionnaire (FFQ) in MBCS [22], and a modified version of the Block Food Frequency Questionnaire in SFBCS [23].…”

Blocking of JB6 Cell Transformation by Tanshinone IIA: Epigenetic Reactivation of Nrf2 Antioxidative Stress Pathway

“…It is evident that oxidative stress plays an important role in carcinogenesis and cancer progression (2). Oxidative stress is caused by an imbalance between systemic reactive oxygen species (ROS) and the body's capability to neutralize ROS, which may result in genomic instability, genetic mutation, and neoplastic transformation, leading to a higher incidence of carcinogenesis.…”

Prognostic evaluation of VEGFA genotypes and haplotypes in a cohort of Brazilian women with non metastatic breast cancer

“…With regards to disease-free survival of non-metastatic breast cancer patients, seven previous studies have explored the role of VEGFA SNPs. 13,38,40,[42][43][44]50 However, the studies differed about design, population characteristics and SNPs selected, and the results must be compared with caution. In relation to rs699947, Maae et al 42 and Sa-Nguanraksa et al 44 found no significant results on disease-free survival, whereas Kidd et al 43 reported an increased risk of breast cancer recurrence (HR D 1.58, 95% CI D 1.06-2.35; p D 0.03) for the haplotype formed by rs699947 C, rs1570360 G and rs2010963 G. The authors claimed that such effect might be related to rs699947 C allele, which was not independently predictive of breast cancer outcomes, but improved the 5-and 8-year predictive accuracy of standard prognostic indicators.…”

“…22,21,12 VEGFA SNPs were shown to affect VEGFA levels in different cell models, 21,[23][24][25] including breast cancer. 26 VEGFA SNPs have also been associated with breast cancer susceptibility, 11,13,23,[26][27][28][29][30][31][32][33][34][35][36][37][38][39] increased risk of progression 13,[40][41][42][43][44] or poor survival. 13,43 However, most of these works focused on the effects of SNPs evaluated separately, and the results from different authors present great disparity.…”