Genetic variation in PRL and PRLR, and relationships with serum prolactin levels and breast cancer risk

Results from a population-based case-control study in Poland

Sarah J. Nyante, Jessica M. Faupel-Badger, Mark E. Sherman, Ruth M. Pfeiffer, Mia M. Gaudet, Roni T. Falk, Abegail A. Andaya, Jolanta Lissowska, Louise A. Brinton, Beata Peplonska, Barbara K. Vonderhaar, Stephen Chanock, Montserrat Garcia-Closas, Jonine D. Figueroa

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Abstract

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.

Original languageEnglish (US)
Article numberR42
JournalBreast Cancer Research
Volume13
Issue number2
DOIs
StatePublished - Apr 6 2011

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Prolactin Receptors
Poland
Prolactin
Case-Control Studies
Breast Neoplasms
Serum
Population
Single Nucleotide Polymorphism
Odds Ratio
Confidence Intervals
Alleles
Linear Models
Genotype
Menstrual Cycle
Immunoassay

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Genetic variation in PRL and PRLR, and relationships with serum prolactin levels and breast cancer risk : Results from a population-based case-control study in Poland. / Nyante, Sarah J.; Faupel-Badger, Jessica M.; Sherman, Mark E.; Pfeiffer, Ruth M.; Gaudet, Mia M.; Falk, Roni T.; Andaya, Abegail A.; Lissowska, Jolanta; Brinton, Louise A.; Peplonska, Beata; Vonderhaar, Barbara K.; Chanock, Stephen; Garcia-Closas, Montserrat; Figueroa, Jonine D.

In: Breast Cancer Research, Vol. 13, No. 2, R42, 06.04.2011.

Research output: Contribution to journalArticle

Nyante, SJ, Faupel-Badger, JM, Sherman, ME, Pfeiffer, RM, Gaudet, MM, Falk, RT, Andaya, AA, Lissowska, J, Brinton, LA, Peplonska, B, Vonderhaar, BK, Chanock, S, Garcia-Closas, M & Figueroa, JD 2011, 'Genetic variation in PRL and PRLR, and relationships with serum prolactin levels and breast cancer risk: Results from a population-based case-control study in Poland', Breast Cancer Research, vol. 13, no. 2, R42. https://doi.org/10.1186/bcr2864
Nyante, Sarah J. ; Faupel-Badger, Jessica M. ; Sherman, Mark E. ; Pfeiffer, Ruth M. ; Gaudet, Mia M. ; Falk, Roni T. ; Andaya, Abegail A. ; Lissowska, Jolanta ; Brinton, Louise A. ; Peplonska, Beata ; Vonderhaar, Barbara K. ; Chanock, Stephen ; Garcia-Closas, Montserrat ; Figueroa, Jonine D. / Genetic variation in PRL and PRLR, and relationships with serum prolactin levels and breast cancer risk : Results from a population-based case-control study in Poland. In: Breast Cancer Research. 2011 ; Vol. 13, No. 2.
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title = "Genetic variation in PRL and PRLR, and relationships with serum prolactin levels and breast cancer risk: Results from a population-based case-control study in Poland",
abstract = "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 Ł{\'o}dź, 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.",
author = "Nyante, {Sarah J.} and Faupel-Badger, {Jessica M.} and Sherman, {Mark E.} and Pfeiffer, {Ruth M.} and Gaudet, {Mia M.} and Falk, {Roni T.} and Andaya, {Abegail A.} and Jolanta Lissowska and Brinton, {Louise A.} and Beata Peplonska and Vonderhaar, {Barbara K.} and Stephen Chanock and Montserrat Garcia-Closas and Figueroa, {Jonine D.}",
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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.

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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DO - 10.1186/bcr2864

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JO - Breast Cancer Research

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