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Association of Prolactin and Its Receptor Gene Regions with Familial Breast Cancer

Division of Molecular Genetic Epidemiology (A.V., K.H., K.W., B.B., A.F.), German Cancer Research Center, D-69120 Heidelberg, Germany; Department of Biosciences at Novum (K.H., A.F.), Karolinska Institute, SE-141 57 Huddinge, Sweden; Institute of Human Genetics (C.R.B., R.K.), University of Heidelberg, D-69120 Heidelberg, Germany; Division of Molecular Gynaeco-Oncology (B.W., R.K.S.), Department of Gynaecology and Obstetrics, Clinical Center University of Cologne, D-50931 Cologne, Germany; Center of Molecular Medicine of Cologne (B.W., R.K.S.), University Hospital of Cologne, D-50924 Cologne, Germany; Department of Gynaecology and Obstetrics (A.M.), Klinikum rechts der Isar, Technical University of Munich, D-81675 Munich, Germany; and Department of Gynaecology and Obstetrics (M.U.), Ludwig-Maximilians-University, D-81377 Munich, Germany

Address all correspondence and requests for reprints to: Annika Vaclavicek, Division of Molecular Genetic Epidemiology C050, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. E-mail: a.vaclavicek{at}dkfz.de.

Context: The contribution of prolactin (PRL) through its receptor (PRLR) to the pathogenesis and progression of human mammary tumors has received recent attention.

Objective: We investigated whether genetic variation in the PRL and PRLR genes is associated with the risk of breast cancer (BC).

Design: We conducted a case-control study with a total of seven single nucleotide polymorphisms (SNPs).

Setting: The study was conducted at an academic research laboratory and university clinics.

Patients and Other Participants: A total of 441 German familial, unrelated BC cases and 552 controls matched by age, ethnicity, and geographical region participated in the study.

Intervention(s): There were no interventions.

Main Outcome Measures(s): SNP genotype and haplotype distributions and haplotype interactions were correlated with the risk of BC.

Results: Two SNPs (rs1341239 and rs12210179) within the PRL promoter regions were significantly associated with increased risk in homozygotes for the variant alleles [odds ratio (OR), 1.67 and 95% confidence interval (CI), 1.11–2.50; and OR, 2.09 and 95% CI, 1.23–3.52, respectively]. The PRL haplotype containing the variant alleles of the promoter SNPs increased significantly the risk of BC (OR 1.42, 95%CI 1.07–1.90). A PRLR haplotype was associated with a significant decrease in BC risk (OR 0.69, 95% CI 0.54–0.89). An increasing number of PRL and PRLR risk haplotypes led to a significant trend of increasing risk for BC (² = 12.15; P = 0.007).

Conclusions: Genetic variation in the PRL and PRLR genes was shown to influence BC risk. Additional studies are needed to further clarify the role of the PRL and PRLR genes in the risk of BC.

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