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Coffee Consumption and CYP1A2*1F Genotype Modify Age at Breast Cancer Diagnosis and Estrogen Receptor Status

¹ Department of Oncology, Clinical Sciences, Lund University; Departments of ² Surgery and ³ Oncology, Lund University Hospital, Lund, Sweden; and ⁴ Faculty of Health and Society, Malmö University, Malmö, Sweden

Requests for reprints: Helena Jernström, Lund University Hospital, Barngatan 2B, SE-221 85 Lund, Sweden. Phone: 46-4617-7619. E-mail: Helena.Jernstrom{at}med.lu.se

CYP1A2 plays a key role in the metabolism of both estrogen and coffee. Women with higher coffee intake and the CYP1A2*1F A/A genotype have a ratio of high 2-hydroxyestrone (2-OHE1) to 16-OHE1. 2-OHE1 is a weak estrogen and may even block the estrogen receptor (ER), whereas 16-OHE1 is procarcinogenic. We hypothesized that moderate to high coffee consumption (2 cups per day) combined with the CYP1A2*1F A/A genotype would be associated with a later age at diagnosis and a greater proportion of ER-negative (ER–) tumors among patients with breast cancer. We genotyped 458 patients with breast cancer (age, 25-99 years) in Lund, Sweden, for CYP1A2*1F. Information on lifestyle factors and tumor characteristics were obtained from preoperative questionnaires and pathology reports. Among patients with CYP1A2*1F A/A (51.3%), moderate to high consumption was associated with a later age at diagnosis compared with low coffee consumption (59.8 versus 52.6 years, P = 0.0004). These patients were also more likely to have ER– tumors than patients with low consumption (14.7% versus 0%, P = 0.018). Coffee was not associated with ER status or age at diagnosis in patients with at least one C allele. Age at diagnosis was not associated with ER status in patients with CYP1A2*1F A/A, but younger patients (<50 years) with at least one C allele were more likely to have ER– tumors compared with older patients (odds ratio, 4.2; 95% confidence interval, 1.9-9.3; P = 0.0002). These findings raise the hypothesis that coffee slows the growth of ER-positive tumors in patients with CYP1A2*1F A/A and may have implications for breast cancer if confirmed. (Cancer Epidemiol Biomarkers Prev 2008;17(4):895–901)