Dataset Information

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: 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.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 ?ód?, 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).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.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.

SUBMITTER: Nyante SJ

PROVIDER: S-EPMC3219205 | biostudies-literature | 2011 Apr

REPOSITORIES: biostudies-literature

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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 SJ Faupel-Badger Jessica M JM Sherman Mark E ME Pfeiffer Ruth M RM Gaudet Mia M MM Falk Roni T RT Andaya Abegail A AA Lissowska Jolanta J Brinton Louise A LA Peplonska Beata B Vonderhaar Barbara K BK Chanock Stephen S Garcia-Closas Montserrat M Figueroa Jonine D JD

Breast cancer research : BCR 20110406 2

<h4>Introduction</h4>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.<h4>Methods</h4>We genotyped 8 PRL and 20 PRLR tag SNPs in 1965 breast cancer cases and 2229 match ...[more]

PMID: 21470416

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Project description:Studies in animals and humans clearly indicate a role for prolactin (PRL) in breast epithelial proliferation, differentiation, and tumorigenesis. Prospective epidemiological studies have also shown that women with higher circulating PRL levels have an increase in risk of breast cancer, suggesting that variability in PRL may also be important in determining a woman's risk.We evaluated genetic variation in the PRL and PRL receptor (PRLR) genes as predictors of plasma PRL levels and breast cancer risk among African-American, Native Hawaiian, Japanese-American, Latina, and White women in the Multiethnic Cohort Study (MEC). We selected single nucleotide polymorphisms (SNPs) from both the public (dbSNP) and private (Celera) databases to construct high density SNP maps that included up to 20 kilobases (kb) upstream of the transcription initiation site and 10 kb downstream of the last exon of each gene, for a total coverage of 59 kb in PRL and 210 kb in PRLR. We genotyped 80 SNPs in PRL and 173 SNPs in PRLR in a multiethnic panel of 349 unaffected subjects to characterize linkage disequilibrium (LD) and haplotype patterns. We sequenced the coding regions of PRL and PRLR in 95 advanced breast cancer cases (19 of each racial/ethnic group) to uncover putative functional variation. A total of 33 and 60 haplotype "tag" SNPs (tagSNPs) that allowed for high predictability (Rh2 > or = 0.70) of the common haplotypes in PRL and PRLR, respectively, were then genotyped in a multiethnic breast cancer case-control study of 1,615 invasive breast cancer cases and 1,962 controls in the MEC. We also assessed the association of common genetic variation with circulating PRL levels in 362 postmenopausal controls without a history of hormone therapy use at blood draw. Because of the large number of comparisons being performed we used a relatively stringent type I error criteria (p < 0.0005) for evaluating the significance of any single association to correct for performing approximately 100 independent tests, close to the number of tagSNPs genotyped for both genes.We observed no significant associations between PRL and PRLR haplotypes or individual SNPs in relation to breast cancer risk. A nominally significant association was noted between prolactin levels and a tagSNP (tagSNP 44, rs2244502) in intron 1 of PRL. This SNP showed approximately a 50% increase in levels between minor allele homozygotes vs. major allele homozygotes. However, this association was not significant (p = 0.002) using our type I error criteria to correct for multiple testing, nor was this SNP associated with breast cancer risk (p = 0.58).In this comprehensive analysis covering 59 kb of the PRL locus and 210 kb of the PRLR locus, we found no significant association between common variation in these candidate genes and breast cancer risk or plasma PRL levels. The LD characterization of PRL and PRLR in this multiethnic population provide a framework for studying these genes in relation to other disease outcomes that have been associated with PRL, as well as for larger studies of plasma PRL levels.

Project description:BackgroundVitamins are involved in various human physiological and biochemical mechanisms due to their antioxidant properties and their ability to enhance the immune response. Deficiency of some serum vitamins has been reported to be associated with an increased risk of developing cancer, including thyroid cancer. However, medical literature dealing with cholecalciferol supplementation was not able to show the potential of this intervention in cancer prevention. The aim of this paper is to highlight the association between lower serum vitamins levels and papillary thyroid cancer occurrence.MethodsThis case-control study was conducted between September 2018 and October 2019. Cases were defined as patients with histologically diagnosed papillary thyroid cancer who underwent thyroidectomy were retrospectively recruited and serum levels of various vitamins were assessed by examining their relationships with clinical, pathological and molecular data (n=51). Controls matched on sex and thyroid surgery were randomly selected from the same population (n=49).ResultsIn this study, serum concentrations of vitamins A and E in neoplastic patients were significantly lower than in controls (1.40 vs. 1.78, P<0.003 and 23.9 vs. 29.1, P<0.003, respectively). Serum concentrations of vitamin D and methylmalonic acid were borderline significantly low (15.6 vs. 17.9, P=0.06 and 100.3 vs. 110.4, P=0.055, respectively), while homocysteine was statistically similar in the two groups. Furthermore, serum vitamin levels were compared with the pathological characteristics of cancer patients, and vitamin D concentrations were significantly lower in BRAF-positive than in BRAF-negative neoplastic patients (8.2 vs. 16.0, P=0.021). On the other hand, no significant differences were observed in the correlation between serum levels of vitamins and other pathological characteristics, in particular with regard to lymph node metastases.ConclusionsIn conclusion, albeit with the analysis of a limited sample, this study highlighted the phenomenon that deficiencies in vitamins A and E can be associated with a higher frequency of occurrence of papillary thyroid cancer.

Dataset Information

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.

Publications

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.

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