TY - JOUR
T1 - Genetic variation in PRL and PRLR, and relationships with serum prolactin levels and breast cancer risk
T2 - Results from a population-based case-control study in Poland
AU - Nyante, Sarah J.
AU - Faupel-Badger, Jessica M.
AU - Sherman, Mark E.
AU - Pfeiffer, Ruth M.
AU - Gaudet, Mia M.
AU - Falk, Roni T.
AU - Andaya, Abegail A.
AU - Lissowska, Jolanta
AU - Brinton, Louise A.
AU - Peplonska, Beata
AU - Vonderhaar, Barbara K.
AU - Chanock, Stephen
AU - Garcia-Closas, Montserrat
AU - Figueroa, Jonine D.
N1 - Funding Information:
The authors would like to thank Pei Chao and Michael Stagner, of Information Management Services, Inc. (Silver Spring, MD, USA), for their work on data management and the study participants and interviewers who took part in the Polish Breast Cancer Study as well as the physicians, pathologists, and nurses from participating centers for their efforts during field work. This research was supported by the Intramural Research Program of the National Cancer Institute (USA). Participating centers in Poland were the Cancer Center and M. Sklodowska-Curie Institute of Oncology in Warsaw, Departments of Epidemiology (coordinating center: Jolanta Lissowska, Alicja Bardin-Mikolajczak, and Witold Zatonski) and Breast Cancer Treatment and Reconstruction (Edward Towpik and Jerzy Giermek), Departments of Surgical Oncology (Pawel Kukawski) and Pathology (Grzegorz Rymkiewicz, Marcin Ligaj, Joanna Barańska, Agnieszka Turowicz, and Włodzimierz Olszewski); Polish Oncological Foundation in Warsaw, Pathology (Dorota Mazepa-Sikora and Włodzimierz Olszewski); Nofer Institute of Occupational Medicine in Łódź (Neonila Szeszenia-Dąbrowska and Beata Peplonska); Medical University in Łódź, Oncology Clinic (Arkadiusz Jeziorski and Janusz Piekarski) and Pathology Department (Radzislaw Kordek, Grazyna Pasz-Walczak, Robert Kubiak, Dorota Kupnicka, and Boguslaw Olborski); Community Copernicus Hospital in Łódź, Department of Surgical Oncology (Zbigniew Morawiec and Mariusz Pawlak); and Polish Mother’s Health Memorial Hospital in Łódź, Departments Surgical Oncology and Breast Diseases (Marcin Faflik, Magdalena Baklinska, Marek Zadrozny, and Boguslaw Westfal) and Clinical Pathomorphology (Stanislaw Lukaszek and Andrzej Kulig).
PY - 2011/4/6
Y1 - 2011/4/6
N2 - Introduction: Studies suggest that high circulating levels of prolactin increase breast cancer risk. It is unclear if genetic variations in prolactin (PRL) or prolactin receptor (PRLR) genes also play a role. Thus, we examined the relationship between single nucleotide polymorphisms (SNPs) in PRL and PRLR, serum prolactin levels and breast cancer risk in a population-based case-control study.Methods: We genotyped 8 PRL and 20 PRLR tag SNPs in 1965 breast cancer cases and 2229 matched controls, aged 20-74, and living in Warsaw or Łódź, Poland. Serum prolactin levels were measured by immunoassay in a subset of 773 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for genotype associations with breast cancer risk were estimated using unconditional logistic regression, adjusted for age and study site. Geometric mean prolactin levels were estimated using linear regression models adjusted for age, study site, blood collection time, and menstrual cycle day (premenopausal women).Results: Three SNPs were associated with breast cancer risk: in premenopausal women, PRLR rs249537 (T vs. C per-allele OR 1.39, 95% CI 1.07 - 1.80, P = 0.01); and in postmenopausal women, PRLR rs7718468 (C vs. T per-allele OR 1.16, 95% CI 1.03 - 1.30, P = 0.01) and PRLR rs13436213 (A vs. G per-allele OR 1.13 95% CI 1.01 - 1.26, P = 0.04). However, mean serum prolactin levels for these SNPs did not vary by genotype (P-trend > 0.05). Other SNPs were associated with serum prolactin levels: PRLR rs62355518 (P-trend = 0.01), PRLR rs10941235 (P-trend = 0.01), PRLR rs1610218 (P-trend = 0.01), PRLR rs34024951 (P-trend = 0.02), and PRLR rs9292575 (P-trend = 0.03) in premenopausal controls and PRL rs849872 (P-trend = 0.01) in postmenopausal controls.Conclusions: Our data provide limited support for an association between common variations in PRLR and breast cancer risk. Altered serum prolactin levels were not associated with breast cancer risk-associated variants, suggesting that common genetic variation is not a strong predictor of prolactin-associated breast cancer risk in this population.
AB - Introduction: Studies suggest that high circulating levels of prolactin increase breast cancer risk. It is unclear if genetic variations in prolactin (PRL) or prolactin receptor (PRLR) genes also play a role. Thus, we examined the relationship between single nucleotide polymorphisms (SNPs) in PRL and PRLR, serum prolactin levels and breast cancer risk in a population-based case-control study.Methods: We genotyped 8 PRL and 20 PRLR tag SNPs in 1965 breast cancer cases and 2229 matched controls, aged 20-74, and living in Warsaw or Łódź, Poland. Serum prolactin levels were measured by immunoassay in a subset of 773 controls. Odds ratios (ORs) and 95% confidence intervals (CIs) for genotype associations with breast cancer risk were estimated using unconditional logistic regression, adjusted for age and study site. Geometric mean prolactin levels were estimated using linear regression models adjusted for age, study site, blood collection time, and menstrual cycle day (premenopausal women).Results: Three SNPs were associated with breast cancer risk: in premenopausal women, PRLR rs249537 (T vs. C per-allele OR 1.39, 95% CI 1.07 - 1.80, P = 0.01); and in postmenopausal women, PRLR rs7718468 (C vs. T per-allele OR 1.16, 95% CI 1.03 - 1.30, P = 0.01) and PRLR rs13436213 (A vs. G per-allele OR 1.13 95% CI 1.01 - 1.26, P = 0.04). However, mean serum prolactin levels for these SNPs did not vary by genotype (P-trend > 0.05). Other SNPs were associated with serum prolactin levels: PRLR rs62355518 (P-trend = 0.01), PRLR rs10941235 (P-trend = 0.01), PRLR rs1610218 (P-trend = 0.01), PRLR rs34024951 (P-trend = 0.02), and PRLR rs9292575 (P-trend = 0.03) in premenopausal controls and PRL rs849872 (P-trend = 0.01) in postmenopausal controls.Conclusions: Our data provide limited support for an association between common variations in PRLR and breast cancer risk. Altered serum prolactin levels were not associated with breast cancer risk-associated variants, suggesting that common genetic variation is not a strong predictor of prolactin-associated breast cancer risk in this population.
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U2 - 10.1186/bcr2864
DO - 10.1186/bcr2864
M3 - Article
C2 - 21470416
AN - SCOPUS:80955130401
SN - 1465-5411
VL - 13
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 2
M1 - R42
ER -