| 1. |
- Arslan, Alan A., et al.
(författare)
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Circulating Estrogen Metabolites and Risk of Breast Cancer in Postmenopausal Women
- 2014
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - 1055-9965 .- 1538-7755. ; 23:7, s. 1290-1297
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Tidskriftsartikel (refereegranskat)abstract
- Background: It has been hypothesized that predominance of the 2-hydroxylation estrogen metabolism pathway over the 16 alpha-hydroxylation pathway may be inversely associated with breast cancer risk. Methods: We examined the associations of invasive breast cancer risk with circulating 2-hydroxyestrone (2-OHE1), 16 alpha-hydroxyestrone (16 alpha-OHE1), and the 2-OHE1: 16 alpha-OHE1 ratio in a case-control study of postmenopausal women nested within two prospective cohorts: the New York University Women's Health Study (NYUWHS) and the Northern Sweden Mammary Screening Cohort (NSMSC), with adjustment for circulating levels of estrone, and additional analyses by tumor estrogen receptor (ER) status. Levels of 2-OHE1 and 16 alpha-OHE1 were measured using ESTRAMET 2/16 assay in stored serum or plasma samples from 499 incident breast cancer cases and 499 controls, who were matched on cohort, age, and date of blood donation. Results: Overall, no significant associations were observed between breast cancer risk and circulating levels of 2-OHE1, 16 alpha-OHE1, or their ratio in either cohort and in combined analyses. For 2-OHE1, there was evidence of heterogeneity by ER status in models adjusting for estrone (P <= 0.03). We observed a protective association of 2-OHE1 with ER + breast cancer [multivariate-adjusted OR for a doubling of 2-OHE1, 0.67 (95% confidence interval [CI], 0.48-0.94; P = 0.02)]. Conclusions: In this study, higher levels of 2-OHE1 were associated with reduced risk of ER + breast cancer in postmenopausal women after adjustment for circulating estrone. Impact: These results suggest that taking into account the levels of parent estrogens and ER status is important in studies of estrogen metabolites and breast cancer.
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| 2. |
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| 3. |
- Belitskaya-Lévy, Ilana, et al.
(författare)
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Characterization of a genomic signature of pregnancy identified in the breast
- 2011
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Ingår i: Cancer Prevention Research. - 1940-6207 .- 1940-6215. ; 4:9, s. 1457-1464
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Tidskriftsartikel (refereegranskat)abstract
- The objective of this study was to comprehensively compare the genomic profiles in the breast of parous and nulliparous postmenopausal women to identify genes that permanently change their expression following pregnancy. The study was designed as a two-phase approach. In the discovery phase, we compared breast genomic profiles of 37 parous with 18 nulliparous postmenopausal women. In the validation phase, confirmation of the genomic patterns observed in the discovery phase was sought in an independent set of 30 parous and 22 nulliparous postmenopausal women. RNA was hybridized to Affymetrix HG_U133 Plus 2.0 oligonucleotide arrays containing probes to 54,675 transcripts, scanned and the images analyzed using Affymetrix GCOS software. Surrogate variable analysis, logistic regression, and significance analysis of microarrays were used to identify statistically significant differences in expression of genes. The false discovery rate (FDR) approach was used to control for multiple comparisons. We found that 208 genes (305 probe sets) were differentially expressed between parous and nulliparous women in both discovery and validation phases of the study at an FDR of 10% and with at least a 1.25-fold change. These genes are involved in regulation of transcription, centrosome organization, RNA splicing, cell-cycle control, adhesion, and differentiation. The results provide initial evidence that full-term pregnancy induces long-term genomic changes in the breast. The genomic signature of pregnancy could be used as an intermediate marker to assess potential chemopreventive interventions with hormones mimicking the effects of pregnancy for prevention of breast cancer.
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| 4. |
- Clendenen, Tess, et al.
(författare)
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Genetic variants in hormone-related genes and risk of breast cancer
- 2013
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Ingår i: PLOS ONE. - SAN FRANCISCO : PLoS, Public Library of Science. - 1932-6203. ; 8:7, s. e69367-
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Tidskriftsartikel (refereegranskat)abstract
- Sex hormones play a key role in the development of breast cancer. Certain polymorphic variants (SNPs and repeat polymorphisms) in hormone-related genes are associated with sex hormone levels. However, the relationship observed between these genetic variants and breast cancer risk has been inconsistent. We conducted a case-control study nested within two prospective cohorts to assess the relationship between specific genetic variants in hormone-related genes and breast cancer risk. In total, 1164 cases and 2111 individually-matched controls were included in the study. We did not observe an association between potential functional genetic polymorphisms in the estrogen pathway, SHBG rs6259, ESR1 rs2234693, CYP19 rs10046 and rs4775936, and UGT1A1 rs8175347, or the progesterone pathway, PGR rs1042838, with the risk of breast cancer. Our results suggest that these genetic variants do not have a strong effect on breast cancer risk.
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| 5. |
- Clendenen, Tess V., et al.
(författare)
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Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer : a nested case-control study
- 2015
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Ingår i: PLOS ONE. - : PLOS one. - 1932-6203. ; 10:10
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Tidskriftsartikel (refereegranskat)abstract
- Genetic polymorphisms in vitamin D metabolism and signaling genes have been inconsistently associated with risk of breast cancer, though few studies have examined SNPs in vitamin D-related genes other than the vitamin D receptor (VDR) gene and particularly have not examined the association with the retinoid X receptor alpha (RXRA) gene which may be a key vitamin D pathway gene. We conducted a nested case-control study of 734 cases and 1435 individually matched controls from a population-based prospective cohort study, the Northern Sweden Mammary Screening Cohort. Tag and functional SNPs were genotyped for the VDR, cytochrome p450 24A1 (CYP24A1), and RXRA genes. We also genotyped specific SNPs in four other genes related to vitamin D metabolism and signaling (GC/VDBP, CYP2R1, DHCR7, and CYP27B1). SNPs in the CYP2R1, DHCR7, and VDBP gene regions that were associated with circulating 25(OH) D concentration in GWAS were also associated with plasma 25(OH) D in our study (p-trend < 0.005). After taking into account the false discovery rate, these SNPs were not significantly associated with breast cancer risk, nor were any of the other SNPs or haplotypes in VDR, RXRA, and CYP24A1. We observed no statistically significant associations between polymorphisms or haplotypes in key vitamin D-related genes and risk of breast cancer. These results, combined with the observation in this cohort and most other prospective studies of no association of circulating 25(OH) D with breast cancer risk, do not support an association between vitamin D and breast cancer risk.
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| 6. |
- Lukanova, Annekatrin, et al.
(författare)
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Human chorionic gonadotropin and alpha-fetoprotein concentrations in pregnancy and maternal risk of breast cancer : a nested case-control study.
- 2008
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Ingår i: American Journal of Epidemiology. - : Oxford University Press (OUP). - 0002-9262 .- 1476-6256. ; 168:11, s. 1284-1291
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Tidskriftsartikel (refereegranskat)abstract
- Pregnancy hormones are believed to be involved in the protection against breast cancer conferred by pregnancy. The authors explored the association of maternal breast cancer with human chorionic gonadotropin (hCG) and alpha-fetoprotein (AFP). In 2001, a case-control study was nested within the Northern Sweden Maternity Cohort, an ongoing study in which blood samples have been collected from first-trimester pregnant women since 1975. Cases (n = 210) and controls (n = 357) were matched for age, parity, and date of blood donation. Concentrations of hCG and AFP were measured by immunoassay. No overall significant association of breast cancer with either hCG or AFP was observed. However, women with hCG levels in the top tertile tended to be at lower risk of breast cancer than women with hCG levels in the lowest tertile in the whole study population and in subgroups of age at sampling, parity, and age at cancer diagnosis. A borderline-significant decrease in risk with high hCG levels was observed in women who developed breast cancer after the median lag time to cancer diagnosis (> or =14 years; odds ratio = 0.53, 95% confidence interval: 0.27, 1.03; P = 0.06). These findings, though very preliminary, are consistent with a possible long-term protective association of breast cancer risk with elevated levels of circulating hCG in the early stages of pregnancy.
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| 7. |
- Lukanova, Annekatrin, et al.
(författare)
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Insulin-like growth factor I in pregnancy and maternal risk of breast cancer
- 2006
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Ingår i: Cancer Epidemiology, Biomarkers and Prevention. - Baltimore : Waverly Press. - 1055-9965 .- 1538-7755. ; 15:12, s. 2489-2493
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Tidskriftsartikel (refereegranskat)abstract
- Background: The role of insulin-like growth factor (IGF)-I in breast cancer remains controversial, despite numerous reports on the association of the hormone with breast cancer or high-risk mammographic densities. We hypothesized that exposure to elevated IGF-I during early pregnancy, a period characterized by intense cell proliferation in the breasts and in the presence of high concentrations of sex steroids, will be associated with increased maternal risk to develop a breast malignancy. Methods: The Northern Sweden Maternity Cohort is an ongoing prospective study, collecting blood samples from first-trimester-pregnant women since 1975 as part of screening for infectious diseases. A case-control study (212 cases and 369 controls) was nested among Northern Sweden Maternity Cohort members who delivered singleton babies. RIA was used to measure IGF-I and IGF-II levels. Conditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (95% CI). Results: Breast cancer risk increased with increasing IGF-I (top tertile OR, 1.7; 95% CI, 1.1-2.7). The association was stronger among the primiparous (OR, 2.2; 95% CI, 1.1-4.4) than in the nonprimiparous women (OR, 1.4; 95% CI, 0.7-2.8). Upper-tertile risks seemed to decrease within the <28-, 28 to 33, and >33-year groups of age at sampling, from 2.5 (0.9-7.6) to 2.1 (0.9-5.0) and 1.2 (0.5-2.5), respectively. There was no association of breast cancer with first-trimester-pregnancy IGF-II. Conclusions: The study offers further evidence that IGF-I is important in breast cancer. Our findings suggest that the adverse effect of IGF-I on the breast may be stronger before the remodeling of the gland induced by a first pregnancy.
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| 8. |
- Lukanova, Annekatrin, et al.
(författare)
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Prediagnostic levels of C-peptide, IGF-I, IGFBP -1, -2 and -3 and risk of endometrial cancer.
- 2004
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Ingår i: International Journal of Cancer. - : Wiley. - 0020-7136 .- 1097-0215. ; 108:2, s. 262-268
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Tidskriftsartikel (refereegranskat)abstract
- Conditions related to chronic hyperinsulinemia, such as obesity, noninsulin dependent diabetes mellitus and polycystic ovary syndrome, are associated with an increased risk of endometrial cancer. Elevated plasma IGF-I and decreased levels of IGF-binding proteins have been shown to be associated with increased risk of several cancer types that are frequent in affluent societies. We investigated for the first time in a prospective study the association of pre-diagnostic blood concentrations of C-peptide (a marker of pancreatic insulin production), IGF-I, IGFBP-1, -2 and -3 with endometrial cancer risk. A case-control study was nested within 3 cohorts in New York (USA), Umeå (Sweden) and Milan (Italy). It included 166 women with primary invasive endometrial cancer and 315 matched controls, of which 44 case and 78 control subjects were premenopausal at recruitment. Endometrial cancer risk increased with increasing levels of C-peptide (ptrend = 0.0002), up to an odds ratio (OR) of 4.76 [95% confidence interval (CI) = 1.91-11.8] for the highest quintile. This association remained after adjustment for BMI and other confounders [OR for the top quintile = 4.40 (1.65-11.7)]. IGFBP-1 levels were inversely related to endometrial cancer [ptrend = 0.002; OR in the upper quintile = 0.30 (0.15-0.62)], but the association was weakened and lost statistical significance after adjustment for confounders [ptrend = 0.06; OR in the upper quintile = 0.49 (0.22-1.07)]. Risk was unrelated to levels of IGF-I, IGFBP-2 and IGFBP-3. Chronic hyperinsulinemia, as reflected by increased circulating C-peptide, is associated with increased endometrial cancer risk. Decrease in the prevalence of chronic hyperinsulinemia, through changes in lifestyle or medication, is expected to prevent endometrial cancer.
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| 9. |
- Lundin, Eva, et al.
(författare)
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Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer
- 2012
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Ingår i: Cancer Epidemiology. - : Elsevier BV. - 1877-7821 .- 1877-783X. ; 36:5, s. 445-452
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Tidskriftsartikel (refereegranskat)abstract
- Background: The role of estrogen and progesterone in the development of endometrial cancer is well documented. Few studies have examined the association of genetic variants in sex hormone-related genes with endometrial cancer risk. Methods: We conducted a case-control study nested within three cohorts to examine the association of endometrial cancer risk with polymorphisms in hormone-related genes among 391 cases (92% postmenopausal at diagnosis) and 712 individually-matched controls. We also examined the association of these polymorphisms with circulating levels of sex hormones and SHBG in a cross-sectional analysis including 596 healthy postmenopausal women at blood donation (controls from this nested case-control study and from a nested case-control study of breast cancer in one of the three cohorts). Results: Adjusting for endometrial cancer risk factors, the A allele of rs4775936 in CYP19 was significantly associated (ORper allele = 1.22, 95% CI = 1.01-1.47, p(trend) = 0.04), while the T allele of rs10046 was marginally associated with increased risk of endometrial cancer (ORper allele = 1.20, 95% CI = 0.99-1.45, p(trend) = 0.06). PGR rs1042838 was also marginally associated with risk (ORper allele = 1.25, 95% CI = 0.96-1.61, p(trend) = 0.09). No significant association was found for the other polymorphisms, i.e. CYP1B1 rs1800440 and rs1056836, UGT1A1 rs8175347, SHBG rs6259 and ESR1 rs2234693. Rs8175347 was significantly associated with postmenopausal levels of estradiol, free estradiol and estrone and rs6259 with SHBG and estradiol. Conclusion: Our findings support an association between genetic variants in CYP19, and possibly PGR, and risk of endometrial cancer. (C) 2012 Elsevier Ltd. All rights reserved.
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| 10. |
- Peri, Suraj, et al.
(författare)
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Defining the genomic signature of the parous breast
- 2012
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Ingår i: BMC Medical Genomics. - : Springer Science and Business Media LLC. - 1755-8794. ; 5, s. 46-
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Tidskriftsartikel (refereegranskat)abstract
- Background: It is accepted that a woman's lifetime risk of developing breast cancer after menopause is reduced by early full term pregnancy and multiparity. This phenomenon is thought to be associated with the development and differentiation of the breast during pregnancy.Methods: In order to understand the underlying molecular mechanisms of pregnancy induced breast cancer protection, we profiled and compared the transcriptomes of normal breast tissue biopsies from 71 parous (P) and 42 nulliparous (NP) healthy postmenopausal women using Affymetrix Human Genome U133 Plus 2.0 arrays. To validate the results, we performed real time PCR and immunohistochemistry.Results: We identified 305 differentially expressed probesets (208 distinct genes). Of these, 267 probesets were up- and 38 down-regulated in parous breast samples; bioinformatics analysis using gene ontology enrichment revealed that up-regulated genes in the parous breast represented biological processes involving differentiation and development, anchoring of epithelial cells to the basement membrane, hemidesmosome and cell-substrate junction assembly, mRNA and RNA metabolic processes and RNA splicing machinery. The down-regulated genes represented biological processes that comprised cell proliferation, regulation of IGF-like growth factor receptor signaling, somatic stem cell maintenance, muscle cell differentiation and apoptosis.Conclusions: This study suggests that the differentiation of the breast imprints a genomic signature that is centered in the mRNA processing reactome. These findings indicate that pregnancy may induce a safeguard mechanism at post-transcriptional level that maintains the fidelity of the transcriptional process.
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