Abstract
Given the racial/ethnic disparities in breast cancer, we evaluated the association between CYP19A1 single nucleotide polymorphisms (SNPs) on disease progression in women with breast cancer from different racial/ethnic backgrounds. This is a cross-sectional analysis of data from 327 women with breast cancer in the Expanded Breast Cancer Registry program of the University of New Mexico. Stored DNA samples were analyzed for CYP19A1 SNPs using a custom designed microarray panel. Genotype-phenotype correlations were analyzed. Of the 384 SNPs, 2 were associated with clinically significant outcomes, the rs4646 and rs12592697. The T allele for the rs4646 was associated with advanced stage of the disease at the time of presentation (odds ratio [OR]:1.8, confidence intervals [CI]: 1.05–3.13, p < 0.05) and a more progressive disease (OR: 2.1 [CI: 1.1–4.0], p = 0.04). For the rs12592697, the variant T allele was more frequent in Hispanic women and associated with a more progressive disease (OR: 2.05 [CI: 1.0–4.0], p = 0.04). However, further analysis according to menopausal status showed that the association between these 2 SNPs with disease progression or the stage at diagnosis are confined only to postmenopausal women. The odds ratios of disease progression among postmenopausal women carrying the T allele for the rs4646 and rs12592697 are 3.05 (1.21, 7.74, p = 0.02) and 3.80 (1.24, 11.6, p = 0.02), respectively. Regardless, differences in disease progression among the different genotypes for both SNPs disappeared after adjustment for treatment. In summary, the rs4646 and the rs12592697 SNPs in CYP19A1 are associated with differences in disease progression in postmenopausal women. However, treatment appears to mitigate the differences in genetic risk.
Highlights
Breast cancer is the most common cancer diagnosed among women in the US regardless of race or ethnicity; disparities in both breast cancer incidence and mortality exist between the various racial/ethnic groups (ACS Cancer Facts & Figures, 2014)
We found that the T allele in both SNPs was associated with overall higher odds of disease progression mostly in the untreated group, while a separate analysis of women on aromatase inhibitors (AI) alone revealed no significant differences in disease progression associated with both SNPs
Two SNPs in CYP19A1 were associated with disease outcomes in the cohort of postmenopausal women diagnosed with breast cancer at our institution
Summary
Breast cancer is the most common cancer diagnosed among women in the US regardless of race or ethnicity; disparities in both breast cancer incidence and mortality exist between the various racial/ethnic groups (ACS Cancer Facts & Figures, 2014). Since genetic polymorphisms in the CYP450 genes vary according to race/ethnicity (Napoli et al, 2009), it is possible that polymorphisms in CYP19A1 may, in part, account for the racial/ethnic differences in the risk and disease behavior of hormone-related diseases such as breast cancer. It may impact disease progression and response to endocrine therapy for breast cancer that could translate into racial differences in disease outcomes. We hypothesize that certain polymorphisms in CYP19A1 are associated with racial/ethnic differences in allele frequencies resulting in differences in the risk of disease progression and stage at presentation among women with breast cancer
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