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Do Placental Genes Affect Maternal Breast Cancer? Association between Offspring's CGB5 and CSH1 Gene Variants and Maternal Breast Cancer Risk

¹ Departments of Environmental Medicine and Medicine and New York University Cancer Institute, New York University School of Medicine; ² Department of Environmental Health Sciences and ³ Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York; and ⁴ Department of Health Studies and ⁵ Departments of Medicine and Human Genetics and Cancer Research Center, The University of Chicago, Chicago, Illinois

Requests for reprints: Habibul Ahsan, Department of Health Studies and Comprehensive Cancer Center, The University of Chicago, 5841 South Maryland Avenue, Suite N102, Chicago, IL 60637. Phone: 773-834-9956; Fax: 773-834-0139; E-mail: habib{at}uchicago.edu.

Key Words: Breast Cancer • Epidemiology • Genetics

The protective effect of full-term pregnancy against breast cancer is thought to be induced by two placental hormones: human chorionic gonadotropin and human chorionic somatotropin hormone (CSH) produced by the placental trophoblastic cells. We hypothesized that variants in placental genes encoding these hormones may alter maternal breast cancer risk subsequent to pregnancy. We conducted a case-control study to examine the association between polymorphisms in a woman's placental (i.e., her offspring's) homologous chorionic gonadotrophin β5 (CGB5) and CSH1 genes and her post-pregnancy breast cancer risk. A total of 293 breast cancer cases and 240 controls with at least one offspring with available DNA were selected from the New York site of the Breast Cancer Family Registry. Three single nucleotide polymorphisms (SNP) in CGB5 and CSH1 genes were genotyped for 844 offspring of the cases and controls. Overall, maternal breast cancer risk did not significantly differ by the offspring's carrier status of the three SNPs. Among women with an earlier age at childbirth (younger than the median age of 26 years), those with a child carrying the variant C allele of CGB5 rs726002 SNP had an elevated breast cancer risk [odds ratio (OR), 2.09; 95% confidence interval (95% CI), 1.17–3.73]. Among women with a later age at childbirth, breast cancer risk did not differ by offspring's carrier status of CGB5 rs726002 SNP (OR, 0.90; 95% CI, 0.53–1.51; P for interaction = 0.04). The findings suggest that placental CGB5 genotype may be predictive of maternal post-pregnancy breast cancer risk among women who give birth early in life. [Cancer Res 2008;68(23):9729–34]