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


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


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


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


METHODS
There were no interventions.


METHODS
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.
Vaclavicek
Annika
A
Division of Molecular Genetic Epidemiology C050, German Cancer Research Center, Im Neuenheimer Feld 580, 69120 Heidelberg, Germany. a.vaclavicek@dkfz.de
Hemminki
Kari
K
Bartram
Claus R
CR
Wagner
Kerstin
K
Wappenschmidt
Barbara
B
Meindl
Alfons
A
Schmutzler
Rita K
RK
Klaes
Rüdiger
R
Untch
Michael
M
Burwinkel
Barbara
B
Försti
Asta
A
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics; D005260:Female; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011388:Prolactin / Q000235:genetics* / Q000378:metabolism; D011981:Receptors, Prolactin / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D011981:Receptors, Prolactin; D011388:Prolactin; D004247:DNA