PURPOSE: Estrogen exposure is involved in both breast cancer susceptibility and the prognosis in patients with breast cancer. Aromatase is involved in the production of estrogens, and altered expression of it might be associated with the prognosis. The aim of this study was to examine the effect of single nucleotide polymorphisms (SNPs) in the aromatase gene, CYP19A1, on the prognosis, and in relation to tumor and patient characteristics in a cohort of breast cancer patients. PATIENTS AND METHODS: The cohort analyzed in this study consisted of 1,257 patients with invasive primary breast cancer. Polymorphisms rs10046, rs4646 and rs700519 were genotyped within this group. RESULTS: The variant genotypes of rs10046 and rs4646 were associated with a lower percentage of HER2-positive tumors. There was no association of rs700519 and rs4646 with disease-free survival (DFS) or overall survival (OS). The variant genotype of rs10046 was significantly associated with a better 5-year DFS (hazards ratio 0.51; 95% CI, 0.32 to 0.81; P=0.004) adjusted for age, nodal status, tumor size grading, and hormone receptor status. This effect appeared to be determined in the subgroup of premenopausal patients. CONCLUSION: SNPs rs10046 and rs4646 may influence the HER2 status of breast cancer tumors, and rs10046 genotypes are associated with an altered DFS. Genotypes of aromatase polymorphisms may influence the prognosis for breast cancer patients not only by affecting the extent of estrogen exposure but also through an alteration in tumor characteristics.
PURPOSE: Estrogen exposure is involved in both breast cancer susceptibility and the prognosis in patients with breast cancer. Aromatase is involved in the production of estrogens, and altered expression of it might be associated with the prognosis. The aim of this study was to examine the effect of single nucleotide polymorphisms (SNPs) in the aromatase gene, CYP19A1, on the prognosis, and in relation to tumor and patient characteristics in a cohort of breast cancerpatients. PATIENTS AND METHODS: The cohort analyzed in this study consisted of 1,257 patients with invasive primary breast cancer. Polymorphisms rs10046, rs4646 and rs700519 were genotyped within this group. RESULTS: The variant genotypes of rs10046 and rs4646 were associated with a lower percentage of HER2-positive tumors. There was no association of rs700519 and rs4646 with disease-free survival (DFS) or overall survival (OS). The variant genotype of rs10046 was significantly associated with a better 5-year DFS (hazards ratio 0.51; 95% CI, 0.32 to 0.81; P=0.004) adjusted for age, nodal status, tumor size grading, and hormone receptor status. This effect appeared to be determined in the subgroup of premenopausal patients. CONCLUSION: SNPs rs10046 and rs4646 may influence the HER2 status of breast cancer tumors, and rs10046 genotypes are associated with an altered DFS. Genotypes of aromatase polymorphisms may influence the prognosis for breast cancerpatients not only by affecting the extent of estrogen exposure but also through an alteration in tumor characteristics.
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Authors: Zaida Garcia-Casado; Angel Guerrero-Zotano; Antonio Llombart-Cussac; Ana Calatrava; Antonio Fernandez-Serra; Amparo Ruiz-Simon; Joaquin Gavila; Miguel A Climent; Sergio Almenar; Jose Cervera-Deval; Josefina Campos; Carlos Vazquez Albaladejo; Antonio Llombart-Bosch; Vicente Guillem; Jose A Lopez-Guerrero Journal: BMC Cancer Date: 2010-02-09 Impact factor: 4.430
Authors: Peter A Fasching; Simon Gayther; Leigh Pearce; Joellen M Schildkraut; Ellen Goode; Falk Thiel; Georgia Chenevix-Trench; Jenny Chang-Claude; Shan Wang-Gohrke; Susan Ramus; Paul Pharoah; Andrew Berchuck Journal: Mol Oncol Date: 2009-02-04 Impact factor: 6.603