Angiogenesis genes, dietary oxidative balance and breast cancer risk and progression: The Breast Cancer Health Disparities Study

作者：Slattery Martha L^*; John Esther M; Torres Mejia Gabriela; Lundgreen Abbie; Lewinger Juan Pablo; Stern Mariana C; Hines Lisa; Baumgartner Kathy B; Giuliano Anna R; Wolff Roger K

来源：International Journal of Cancer, 2014, 134(3): 629-644.

DOI：10.1002/ijc.28377

• breast cancer
• FLT1
• KDR
• NOS2A
• TEK
• VEGFA
• diet
• antioxidants
• survival
• Hispanic

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 (one SNP), FLT1 (35 SNPs), HIF1A (four SNPs), KDR (19 SNPs), MPO (one SNP), NOS2A (15 SNPs), TEK (40 SNPs) and VEGFA (eight SNPs) and breast cancer risk among Hispanic (2,111 cases and 2,597 controls) and non-Hispanic white (1,481 cases and 1,586 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 (p(ARTP)=0.03) and with breast cancer survival (p(ARTP)=0.01). KDR was of borderline significance overall (p(ARTP)=0.07), although significantly associated with breast cancer in both low and intermediate Native American (NA) ancestry groups (p(ARTP)=0.02) and estrogen receptor (ER)+/progesterone receptor (PR)- tumor phenotype (p(ARTP)=0.008). Both VEGFA and NOS2A were associated with ER-/PR- tumor phenotype (p(ARTP)=0.01 and p(ARTP)=0.04, respectively). FLT1 was associated with breast cancer survival among those with low NA ancestry (p(ARTP)=0.009). With respect to diet, having a higher dietary oxidative balance score (DOBS) was significantly associated with lower breast cancer risk [odds ratio (OR) 0.74, 95% confidence interval (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.
What's new? In breast cancer, interactions between dietary and genetic factors may play an important role overseeing the growth of new blood vessels, or angiogenesis, and subsequent tumor development and progression. This study shows, however, that while dietary intake of antioxidants and pro-oxidants is associated with breast cancer risk, the influence of angiogenesis-related genetic factors on this association is minimal. Of greater significance appear to be variations in the tyrosine kinase receptors TEK, KDR, and FLT1, which were linked to breast cancer risk and survival. These genes may be targets for novel anti-breast cancer treatments.

• 出版日期2014-2-1