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Lenner, Per
Publications (10 of 116) Show all publications
Gaudet, M. M., Deubler, E. L., Kelly, R. S., Diver, W. R., Teras, L. R., Hodge, J. M., . . . Kyrtopoulos, S. A. (2019). Blood Levels of Cadmium and Lead in Relation to Breast Cancer Risk in Three Prospective Cohorts.. International Journal of Cancer, 144(5), 1010-1016
Open this publication in new window or tab >>Blood Levels of Cadmium and Lead in Relation to Breast Cancer Risk in Three Prospective Cohorts.
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2019 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 144, no 5, p. 1010-1016Article in journal (Refereed) Published
Abstract [en]

Cadmium and lead have been classified as carcinogens by the International Agency for Research on Cancer. However, their associations with breast cancer risk are unknown despite their persistence in the environment and ubiquitous human exposure. We examined associations of circulating levels of cadmium and lead with breast cancer risk in three case-control studies nested within the Cancer Prevention Study-II (CPS-II) LifeLink Cohort, European Prospective Investigation into Cancer and Nutrition - Italy (EPIC-Italy), and the Northern Sweden Health and Disease Study (NSHDS) cohorts. Metal levels were measured in stored erythrocytes from 1,435 cases and 1,433 controls using inductively coupled plasma-mass spectrometry. Summary relative risks (RR) and 95% confidence intervals (CI) were calculated using random-effects models with each study result weighted by the within- and between-study variances. I2 values were calculated to estimate proportion of between study variation. Using common cut-points, cadmium levels were not associated with breast cancer risk in the CPS-II cohort (continuous RR=1.01, 95% CI 0.76 - 1.34), but were inversely associated with risk in the EPIC- Italy (continuous RR=0.80, 95% CI 0.61 - 1.03) and NSHDS cohorts (continuous RR=0.73, 95% CI 0.54 - 0.97). The inverse association was also evident in the meta-analysis (continuous RR=0.84, 95% CI 0.69 - 1.01) with low between-study heterogeneity. Large differences in lead level distributions precluded a meta-analysis of their association with breast cancer risk; no associations were found in the three studies. Adult cadmium and lead levels were not associated with higher risk of breast cancer in our large meta-analysis. 

Place, publisher, year, edition, pages
Wiley-Blackwell, 2019
Keywords
breast cancer, cadmium, lead
National Category
Occupational Health and Environmental Health Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-152113 (URN)10.1002/ijc.31805 (DOI)000455041700009 ()30117163 (PubMedID)
Funder
Swedish Research CouncilVästerbotten County Council
Available from: 2018-09-27 Created: 2018-09-27 Last updated: 2019-01-28Bibliographically approved
Santucci-Pereira, J., Zeleniuch-Jacquotte, A., Afanasyeva, Y., Zhong, H., Slifker, M., Peri, S., . . . Russo, J. (2019). Genomic signature of parity in the breast of premenopausal women. Breast Cancer Research, 21(1), Article ID 46.
Open this publication in new window or tab >>Genomic signature of parity in the breast of premenopausal women
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2019 (English)In: Breast Cancer Research, ISSN 1465-5411, E-ISSN 1465-542X, Vol. 21, no 1, article id 46Article in journal (Refereed) Published
Abstract [en]

BACKGROUND: Full-term pregnancy (FTP) at an early age confers long-term protection against breast cancer. Previously, we reported that a FTP imprints a specific gene expression profile in the breast of postmenopausal women. Herein, we evaluated gene expression changes induced by parity in the breast of premenopausal women.

METHODS: Gene expression profiling of normal breast tissue from 30 nulliparous (NP) and 79 parous (P) premenopausal volunteers was performed using Affymetrix microarrays. In addition to a discovery/validation analysis, we conducted an analysis of gene expression differences in P vs. NP women as a function of time since last FTP. Finally, a laser capture microdissection substudy was performed to compare the gene expression profile in the whole breast biopsy with that in the epithelial and stromal tissues.

RESULTS: Discovery/validation analysis identified 43 differentially expressed genes in P vs. NP breast. Analysis of expression as a function of time since FTP revealed 286 differentially expressed genes (238 up- and 48 downregulated) comparing all P vs. all NP, and/or P women whose last FTP was less than 5 years before biopsy vs. all NP women. The upregulated genes showed three expression patterns: (1) transient: genes upregulated after FTP but whose expression levels returned to NP levels. These genes were mainly related to immune response, specifically activation of T cells. (2) Long-term changing: genes upregulated following FTP, whose expression levels decreased with increasing time since FTP but did not return to NP levels. These were related to immune response and development. (3) Long-term constant: genes that remained upregulated in parous compared to nulliparous breast, independently of time since FTP. These were mainly involved in development/cell differentiation processes, and also chromatin remodeling. Lastly, we found that the gene expression in whole tissue was a weighted average of the expression in epithelial and stromal tissues.

CONCLUSIONS: Genes transiently activated by FTP may have a role in protecting the mammary gland against neoplastically transformed cells through activation of T cells. Furthermore, chromatin remodeling and cell differentiation, represented by the genes that are maintained upregulated long after the FTP, may be responsible for the lasting preventive effect against breast cancer.

Keywords
Breast cancer risk, Breast differentiation, Gene expression profiling, Immune response, Normal breast transcriptome, Parous and nulliparous breast transcriptome, Pregnancy
National Category
Medical Genetics Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-158788 (URN)10.1186/s13058-019-1128-x (DOI)000463748600001 ()30922380 (PubMedID)2-s2.0-85063811942 (Scopus ID)
Available from: 2019-05-08 Created: 2019-05-08 Last updated: 2019-05-16Bibliographically approved
Campanella, G., Gunter, M. J., Polidoro, S., Krogh, V., Palli, D., Panico, S., . . . Chadeau-Hyam, M. (2018). Epigenome-wide association study of adiposity and future risk of obesity-related diseases. International Journal of Obesity, 42(12), 2022-2035
Open this publication in new window or tab >>Epigenome-wide association study of adiposity and future risk of obesity-related diseases
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2018 (English)In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 42, no 12, p. 2022-2035Article in journal (Refereed) Published
Abstract [en]

Background: Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction.

Methods: DNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waist-height ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population.

Results: We identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P = 9.07×10−8 to 3.27×10−18) and lower transcriptional activity of the full-length isoform of ABCG1 (P = 6.00×10−7), higher triglyceride levels (P = 5.37×10−9) and higher triglycerides-to-HDL cholesterol ratio (P = 1.03×10−10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P < 1.6×10−3) and one intergenic locus on chromosome 1 was inversely associated with myocardial infarction (P < 1.25×10−3), independently of obesity and established risk factors.

Conclusion: Our results suggest that epigenetic changes, in particular altered DNA methylation patterns, may be an intermediate biomarker at the intersection of obesity and obesity-related diseases, and could offer clues as to underlying biological mechanisms.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Endocrinology and Diabetes Nutrition and Dietetics
Identifiers
urn:nbn:se:umu:diva-154895 (URN)10.1038/s41366-018-0064-7 (DOI)000452830800009 ()29713043 (PubMedID)
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-01-07Bibliographically approved
Campanella, G., Gunter, M. J., Polidoro, S., Krogh, V., Palli, D., Panico, S., . . . Chadeau-Hyam, M. (2018). Epigenome-wide association study of adiposity and future risk of obesity-related diseases. International Journal of Obesity, 42(12), 2022-2035
Open this publication in new window or tab >>Epigenome-wide association study of adiposity and future risk of obesity-related diseases
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2018 (English)In: International Journal of Obesity, ISSN 0307-0565, E-ISSN 1476-5497, Vol. 42, no 12, p. 2022-2035Article in journal (Refereed) Published
Abstract [en]

Background Obesity is an established risk factor for several common chronic diseases such as breast and colorectal cancer, metabolic and cardiovascular diseases; however, the biological basis for these relationships is not fully understood. To explore the association of obesity with these conditions, we investigated peripheral blood leucocyte (PBL) DNA methylation markers for adiposity and their contribution to risk of incident breast and colorectal cancer and myocardial infarction. Methods DNA methylation profiles (Illumina Infinium® HumanMethylation450 BeadChip) from 1941 individuals from four population-based European cohorts were analysed in relation to body mass index, waist circumference, waist-hip and waistheight ratio within a meta-analytical framework. In a subset of these individuals, data on genome-wide gene expression level, biomarkers of glucose and lipid metabolism were also available. Validation of methylation markers associated with all adiposity measures was performed in 358 individuals. Finally, we investigated the association of obesity-related methylation marks with breast, colorectal cancer and myocardial infarction within relevant subsets of the discovery population. Results We identified 40 CpG loci with methylation levels associated with at least one adiposity measure. Of these, one CpG locus (cg06500161) in ABCG1 was associated with all four adiposity measures (P=9.07×10−8 to 3.27×10−18) and lower transcriptional activity of the full-length isoform of ABCG1 (P=6.00×10−7), higher triglyceride levels (P=5.37×10−9) and higher triglycerides-to-HDL cholesterol ratio (P=1.03×10−10). Of the 40 informative and obesity-related CpG loci, two (in IL2RB and FGF18) were significantly associated with colorectal cancer (inversely, P<1.6×10−3) and one intergenic locus on chromosome 1 was inversely associated with myocardial infarction (P<1.25×10−3), independently of obesity and established risk factors. Conclusion Our results suggest that epigenetic changes, in particular altered DNA methylation patterns, may be an intermediate biomarker at the intersection of obesity and obesity-related diseases, and could offer clues as to underlying biological mechanisms.

Place, publisher, year, edition, pages
Nature Publishing Group, 2018
National Category
Endocrinology and Diabetes
Identifiers
urn:nbn:se:umu:diva-154848 (URN)10.1038/s41366-018-0064-7 (DOI)000452830800009 ()29713043 (PubMedID)2-s2.0-85046105580 (Scopus ID)
Funder
EU, European Research Council, 232997
Available from: 2019-01-07 Created: 2019-01-07 Last updated: 2019-01-07Bibliographically approved
Vermeulen, R., Saberi Hosnijeh, F., Bodinier, B., Portengen, L., Liquet, B., Garrido-Manriquez, J., . . . Liao, S.-F. (2018). Pre-diagnostic blood immune markers, incidence and progression of B-cell lymphoma and multiple myeloma: univariate and functionally informed multivariate analyses. International Journal of Cancer, 143(6), 1335-1347
Open this publication in new window or tab >>Pre-diagnostic blood immune markers, incidence and progression of B-cell lymphoma and multiple myeloma: univariate and functionally informed multivariate analyses
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2018 (English)In: International Journal of Cancer, ISSN 0020-7136, E-ISSN 1097-0215, Vol. 143, no 6, p. 1335-1347Article in journal (Refereed) Published
Abstract [en]

Recent prospective studies have shown that dysregulation of the immune system may precede the development of B‐cell lymphomas (BCL) in immunocompetent individuals. However, to date, the studies were restricted to a few immune markers, which were considered separately. Using a nested case–control study within two European prospective cohorts, we measured plasma levels of 28 immune markers in samples collected a median of 6 years before diagnosis (range 2.01–15.97) in 268 incident cases of BCL (including multiple myeloma [MM]) and matched controls. Linear mixed models and partial least square analyses were used to analyze the association between levels of immune marker and the incidence of BCL and its main histological subtypes and to investigate potential biomarkers predictive of the time to diagnosis. Linear mixed model analyses identified associations linking lower levels of fibroblast growth factor‐2 (FGF‐2 p = 7.2 × 10−4) and transforming growth factor alpha (TGF‐α, p = 6.5 × 10−5) and BCL incidence. Analyses stratified by histological subtypes identified inverse associations for MM subtype including FGF‐2 (p = 7.8 × 10−7), TGF‐α (p = 4.08 × 10−5), fractalkine (p = 1.12 × 10−3), monocyte chemotactic protein‐3 (p = 1.36 × 10−4), macrophage inflammatory protein 1‐alpha (p = 4.6 × 10−4) and vascular endothelial growth factor (p = 4.23 × 10−5). Our results also provided marginal support for already reported associations between chemokines and diffuse large BCL (DLBCL) and cytokines and chronic lymphocytic leukemia (CLL). Case‐only analyses showed that Granulocyte‐macrophage colony stimulating factor levels were consistently higher closer to diagnosis, which provides further evidence of its role in tumor progression. In conclusion, our study suggests a role of growth‐factors in the incidence of MM and of chemokine and cytokine regulation in DLBCL and CLL.

Place, publisher, year, edition, pages
John Wiley & Sons, 2018
Keywords
cytokine, lymphoma, mixed-effect modeling, multiple myeloma, multivariate models, prospective cohort, time to diagnosis
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-147948 (URN)10.1002/ijc.31536 (DOI)000441128700007 ()29667176 (PubMedID)
Available from: 2018-05-23 Created: 2018-05-23 Last updated: 2018-09-13Bibliographically approved
Göhler, S., Da Silva Filho, M. I., Johansson, R., Enquist-Olsson, K., Henriksson, R., Hemminki, K., . . . Försti, A. (2017). Functional germline variants in driver genes of breast cancer. Cancer Causes and Control, 28(4), 259-271
Open this publication in new window or tab >>Functional germline variants in driver genes of breast cancer
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2017 (English)In: Cancer Causes and Control, ISSN 0957-5243, E-ISSN 1573-7225, Vol. 28, no 4, p. 259-271Article in journal (Refereed) Published
Abstract [en]

Purpose Germline mutations in tumour suppressor genes cause various cancers. These genes are also somatically mutated in sporadic tumours. We hypothesized that there may also be cancer-related germline variants in the genes commonly mutated in sporadic breast tumours. Methods After excluding the well-characterized breast cancer (BC) genes, we screened 15 novel genes consistently classified as BC driver genes in next-generation sequencing approaches for single nucleotide polymorphisms (SNPs). Altogether 40 SNPs located in the core promoter, 5'- and 3'-UTR or which were nonsynonymous SNPs were genotyped in 782 Swedish incident BC cases and 1,559 matched controls. After statistical analyses, further evaluations related to functional prediction and signatures of selection were performed. Results TBX3 was associated with BC risk (rs2242442: OR = 0.76, 95% CI 0.64-0.92, dominant model) and with less aggressive tumour characteristics. An association with BC survival and aggressive tumour characteristics was detected for the genes ATR (rs2227928: HR = 1.63; 95% CI 1.00-2.64, dominant model), RUNX1 (rs17227210: HR = 3.50, 95% CI 1.42-8.61, recessive model) and TTN (rs2303838: HR = 2.36; 95% CI 1.04-5.39; rs2042996: HR = 2.28; 95% CI 1.19-4.37, recessive model). According to the experimental ENCODE data all these SNPs themselves or SNPs in high linkage disequilibrium with them (r (2) ae<yen> 0.80) were located in regulatory regions. RUNX1 and TTN showed also several signatures of positive selection. Conclusion The study gave evidence that germline variants in BC driver genes may have impact on BC risk and/or survival. Future studies could discover further germline variants in known or so far unknown driver genes which contribute to cancer development.

Place, publisher, year, edition, pages
Dordrecht: Springer, 2017
Keywords
Breast cancer, Driver genes, Germline variants, Case-control study, Single nucleotide polymorphism
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-134217 (URN)10.1007/s10552-017-0849-3 (DOI)000398480200001 ()28238063 (PubMedID)
Available from: 2017-06-16 Created: 2017-06-16 Last updated: 2018-06-09Bibliographically approved
Göhler, S., Da Silva Filho, M. I., Johansson, R., Enquist-Olsson, K., Henriksson, R., Hemminki, K., . . . Försti, A. (2016). Impact of functional germline variants and a deletion polymorphism in APOBEC3A and APOBEC3B on breast cancer risk and survival in a Swedish study population. Journal of Cancer Research and Clinical Oncology, 142(1), 273-276
Open this publication in new window or tab >>Impact of functional germline variants and a deletion polymorphism in APOBEC3A and APOBEC3B on breast cancer risk and survival in a Swedish study population
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2016 (English)In: Journal of Cancer Research and Clinical Oncology, ISSN 0171-5216, E-ISSN 1432-1335, Vol. 142, no 1, p. 273-276Article in journal (Refereed) Published
Abstract [en]

Purpose: The C -> T mutation signature caused by APOBEC family members contributes to the development of breast cancer (BC). Also overexpression of APOBEC3B and a similar to 29. 5-kb deletion polymorphism between APOBEC3A and APOBEC3B have been associated with increased BC risk. Methods: We investigated in a population-based study, with 782 Swedish BC cases and 1559 controls, associations between potentially functional germline variants in APOBEC3A or APOBEC3B gene and BC risk and survival. Additionally, we identified deletion polymorphism carriers and explored possible associations with BC. Results: No evidence of association between any germline variant, including the deletion polymorphism, and BC risk or survival was observed. Only APOBEC3A promoter polymorphism rs5757402 was associated with low stage (OR = 0.69, 95 % CI 0.50-0.96, dominant model). Conclusion: The reported association between the deletion polymorphism and BC risk was not confirmed in the Swedish population, nor did any genotyped germline variant show any association with BC risk or survival.

Place, publisher, year, edition, pages
Springer, 2016
Keywords
Breast cancer, APOBEC3, Germline variants, Single-nucleotide polymorphism, Deletion polymorphism
National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-118269 (URN)10.1007/s00432-015-2038-7 (DOI)000370172900028 ()26320772 (PubMedID)
Available from: 2016-03-16 Created: 2016-03-14 Last updated: 2018-06-07Bibliographically approved
Clendenen, T. V., Ge, W., Koenig, K. L., Axelsson, T., Liu, M., Afanasyeva, Y., . . . Zeleniuch-Jacquotte, A. (2015). Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer: a nested case-control study. PLoS ONE, 10(10), Article ID e0140478.
Open this publication in new window or tab >>Genetic Polymorphisms in Vitamin D Metabolism and Signaling Genes and Risk of Breast Cancer: a nested case-control study
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2015 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 10, no 10, article id e0140478Article in journal (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
PLOS one, 2015
National Category
Cancer and Oncology Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-111478 (URN)10.1371/journal.pone.0140478 (DOI)000363248400054 ()26488576 (PubMedID)
Available from: 2015-12-10 Created: 2015-11-13 Last updated: 2018-08-31Bibliographically approved
Thomsen, H., da Silva Filho, M. I., Woltmann, A., Johansson, R., Eyfjord, J. E., Hamann, U., . . . Foersti, A. (2015). Inbreeding and homozygosity in breast cancer survival. Scientific Reports, 5, Article ID 16467.
Open this publication in new window or tab >>Inbreeding and homozygosity in breast cancer survival
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2015 (English)In: Scientific Reports, ISSN 2045-2322, E-ISSN 2045-2322, Vol. 5, article id 16467Article in journal (Refereed) Published
Abstract [en]

Genome-wide association studies (GWASs) help to understand the effects of single nucleotide polymorphisms (SNPs) on breast cancer (BC) progression and survival. We performed multiple analyses on data from a previously conducted GWAS for the influence of individual SNPs, runs of homozygosity (ROHs) and inbreeding on BC survival. (I.) The association of individual SNPs indicated no differences in the proportions of homozygous individuals among short-time survivors (STSs) and long-time survivors (LTSs). (II.) The analysis revealed differences among the populations for the number of ROHs per person and the total and average length of ROHs per person and among LTSs and STSs for the number of ROHs per person. (III.) Common ROHs at particular genomic positions were nominally more frequent among LTSs than in STSs. Common ROHs showed significant evidence for natural selection (iHS, Tajima's D, Fay-Wu's H). Most regions could be linked to genes related to BC progression or treatment. (IV.) Results were supported by a higher level of inbreeding among LTSs. Our results showed that an increased level of homozygosity may result in a preference of individuals during BC treatment. Although common ROHs were short, variants within ROHs might favor survival of BC and may function in a recessive manner.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-112244 (URN)10.1038/srep16467 (DOI)000364455700001 ()26558712 (PubMedID)
Available from: 2015-12-10 Created: 2015-12-04 Last updated: 2018-06-07Bibliographically approved
Arslan, A. A., Koenig, K. L., Lenner, P., Afanasyeva, Y., Shore, R. E., Chen, Y., . . . Zeleniuch-Jacquotte, A. (2014). Circulating Estrogen Metabolites and Risk of Breast Cancer in Postmenopausal Women. Cancer Epidemiology, Biomarkers and Prevention, 23(7), 1290-1297
Open this publication in new window or tab >>Circulating Estrogen Metabolites and Risk of Breast Cancer in Postmenopausal Women
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2014 (English)In: Cancer Epidemiology, Biomarkers and Prevention, ISSN 1055-9965, E-ISSN 1538-7755, Vol. 23, no 7, p. 1290-1297Article in journal (Refereed) Published
Abstract [en]

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.

National Category
Cancer and Oncology
Identifiers
urn:nbn:se:umu:diva-98455 (URN)10.1158/1055-9965.EPI-14-0009 (DOI)000345273700018 ()2-s2.0-84903985341 (Scopus ID)
Available from: 2015-02-02 Created: 2015-01-22 Last updated: 2018-06-07Bibliographically approved
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