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Nutritional Epidemiology

The Protective Association of High Plasma Enterolactone with Breast Cancer Is Reasonably Robust in Women with Polymorphisms in the Estrogen Receptor and β Genes^1,2,3

⁴ Department of Clinical Sciences, Nutrition Epidemiology ⁵ Department of Laboratory Medicine, Clinical Chemistry ⁶ Department of Laboratory Medicine, Medical Microbiology, Lund University, SE-20502 Malmö, Sweden ⁷ Department of Laboratory Medicine, Division of Clinical Chemistry and Pharmacology ⁸ Department of Clinical Sciences, Oncology, Lund University, Lund SE-22185, Sweden ⁹ Institute for Preventive Medicine, Nutrition and Cancer, Folkhälsan Research Center and Division of Clinical Chemistry, University of Helsinki, FIN-00014 Helsinki, Finland

It is plausible that polymorphisms in the estrogen receptor and β genes (ESR1 and ESR2) may modulate the association between enterolactone and breast cancer. Seven polymorphisms in ESR1 (rs827422, rs1709184, rs2347867, rs3020328, rs72207, rs2982896, and rs2234693) and 5 polymorphisms in ESR2 (rs915057, rs1269056, rs1256033, rs3020450, and rs3020443) were selected. The risk of breast cancer for these polymorphisms was estimated among 542 cases and 1076 matched controls from the population-based Malmö Diet and Cancer cohort. The joint effect of these polymorphisms and enterolactone was estimated among those individuals about whom we had information on enterolactone blood concentration (365 cases and 728 controls). Breast cancer risk was not significantly associated with any of the selected polymorphisms. We found a tendency for an interaction between a polymorphism in intron 3 of ESR1 (rs2347867) and enterolactone concentration (P = 0.07). Breast cancer and enterolactone concentration were not associated among those homozygous for the major allele (A) (P = 0.93), whereas we found an inverse association among carriers of the minor allele (G) (P = 0.007). None of the other polymorphisms seem to modify the association between enterolactone and breast cancer. This study suggests that the protective association of enterolactone is reasonably robust across the investigated genotypes. The suggested interaction between enterolactone concentration and rs2347867 needs to be confirmed in larger samples.

^* To whom correspondence should be addressed. E-mail: Emily.Sonestedt{at}med.lu.se.

Manuscript received 30 October 2008. Initial review completed 12 December 2008. Revision accepted 16 February 2009.