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Association of prolactin and its receptor gene regions with familial breast cancer.

Vaclavicek A, Hemminki K, Bartram CR, Wagner K, Wappenschmidt B, Meindl A, Schmutzler RK, Klaes R, Untch M, Burwinkel B, Försti A

Division of Molecular Genetic Epidemiology C050, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. a.vaclavicek@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 (chi(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.

Published 7 April 2006 in J Clin Endocrinol Metab, 91(4): 1513-9.
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