Alcohol consumption and breast tumor gene expression

Wang, Jun; Heng, Yujing J.; Eliassen, A. Heather; Tamimi, Rulla M.; Hazra, Aditi; Carey, Vincent J.; Ambrosone, Christine B.; Andrade, Victor Piana de; Brufsky, Adam; Couch, Fergus J.; King, Tari A.; Modugno, Francesmary; Vachon, Celine M.; Hunter, David J.; Beck, Andrew H.; Hankinson, Susan E.

doi:10.1186/s13058-017-0901-y

Cited by 23 publications

(29 citation statements)

References 51 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The protocol to obtain RNA from FFPE tissues was published previously (33). Gene expression data were obtained in two batches using microarrays performed in 2012-2014 using the Glue Grant Human Transcriptome Arrays (HTA) 3.0 prerelease version (Affymetrix, Santa Clara; ref.…”

Section: Gene Expression Datamentioning

confidence: 99%

PAM50 Molecular Intrinsic Subtypes in the Nurses' Health Study Cohorts

Kensler

Sankar

Wang

et al. 2019

Cancer Epidemiology, Biomarkers &Amp; Prevention

Self Cite

View full text Add to dashboard Cite

Background: Modified median and subgroup-specific gene centering are two essential preprocessing methods to assign breast cancer molecular subtypes by PAM50. We evaluated the PAM50 subtypes derived from both methods in a subset of Nurses' Health Study (NHS) and NHSII participants; correlated tumor subtypes by PAM50 with IHC surrogates; and characterized the PAM50 subtype distribution, proliferation scores, and risk of relapse with proliferation and tumor size weighted (ROR-PT) scores in the NHS/NHSII. Methods: PAM50 subtypes, proliferation scores, and ROR-PT scores were calculated for 882 invasive breast tumors and 695 histologically normal tumor-adjacent tissues. Cox proportional hazards models evaluated the relationship between PAM50 subtypes or ROR-PT scores/groups with recurrence-free survival (RFS) or distant RFS. Results: PAM50 subtypes were highly comparable between the two methods. The agreement between tumor subtypes by PAM50 and IHC surrogates improved to fair when Luminal subtypes were grouped together. Using the modified median method, our study consisted of 46% Luminal A, 18% Luminal B, 14% HER2-enriched, 15% Basal-like, and 8% Normal-like subtypes; 53% of tumoradjacent tissues were Normal-like. Women with the Basallike subtype had a higher rate of relapse within 5 years. HER2-enriched subtypes had poorer outcomes prior to 1999. Conclusions: Either preprocessing method may be utilized to derive PAM50 subtypes for future studies. The majority of NHS/NHSII tumor and tumor-adjacent tissues were classified as Luminal A and Normal-like, respectively. Impact: Preprocessing methods are important for the accurate assignment of PAM50 subtypes. These data provide evidence that either preprocessing method can be used in epidemiologic studies.

show abstract

Section: Gene Expression Datamentioning

confidence: 99%

PAM50 Molecular Intrinsic Subtypes in the Nurses' Health Study Cohorts

Kensler

Sankar

Wang

et al. 2019

Cancer Epidemiology, Biomarkers &Amp; Prevention

Self Cite

View full text Add to dashboard Cite

show abstract

“…Our gene expression data was obtained from FFPE tissue blocks preserved for approximately ~ 20 years (median year of diagnosis was 1999), and RNA degradation maybe of concern. We performed pilot work and showed high correlations between ESR1 , PGR , and ERBB2 expression with ER, PR, and ER2 immunohistochemistry staining [ 28 , 29 ]. Our findings are unlikely to be affected by x-ray exposures from mammographic screening, since approximately 80% of women had regular screening (i.e., in each 2 year of the follow up period before diagnosis) [ 58 ] and there was little variability by screening intensity/frequency.…”

Section: Discussionmentioning

confidence: 99%

“…Normal-adjacent tissues were obtained > 1 cm away from the tumor edge. A detailed protocol has been published previously [ 28 – 30 ] (microarray data accession number: GSE115577). In brief, we measured gene expression using Affymetrix Glue Grant Human Transcriptome Array 3.0 (hGlue 3.0) for samples processed in 2012–2014 and Human Transcriptome Array 2.0 (HTA 2.0) microarray chips (Affymetrix, Santa Clara, CA, USA) for samples processed in 2015–2018.…”

Section: Methodsmentioning

confidence: 99%

“…All microarrays were scanned with the GeneChip® Scanner 3000 7G (Affymetrix, Santa Clara, CA, USA). We normalized gene expression data using robust multi-array average (RMA; Affymetrix Power Tools (ATP)), and performed sample quality control using Affymetrix Power Tools probeset summarization based metrics [ 28 , 29 ]. A total of 2160 FFPE samples were assayed.…”

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Low dose environmental radon exposure and breast tumor gene expression

et al. 2020

Self Cite

View full text Add to dashboard Cite

Background The International Agency for Research on Cancer classified radon and its decay-products as Group-1-human-carcinogens, and with the current knowledge they are linked specifically to lung cancer. Biokinetic models predict that radon could deliver a carcinogenic dose to breast tissue. Our previous work suggested that low-dose radon was associated with estrogen-receptor (ER)-negative breast cancer risk. However, there is limited research to examine the role of radon in breast cancer biology at the tissue level. We aim to understand molecular pathways linking radon exposure with breast cancer biology using transcriptome-wide-gene-expression from breast tumor and normal-adjacent tissues. Methods Our study included 943 women diagnosed with breast cancer from the Nurses’ Health Study (NHS) and NHSII. We estimated cumulative radon concentration for each participant up-to the year of breast cancer diagnosis by linking residential addresses with a radon exposure model. Transcriptome-wide-gene-expression was measured with the Affymetrix-Glue-Human-Transcriptome-Array-3.0 and Human-Transcriptome-Array-2.0. We performed covariate-adjusted linear-regression for individual genes and further employed pathway-analysis. All analyses were conducted separately for tumor and normal-adjacent samples and by ER-status. Results No individual gene was associated with cumulative radon exposure in ER-positive tumor, ER-negative tumor, or ER-negative normal-adjacent tissues at FDR < 5%. In ER-positive normal-adjacent samples, PLCH 2—reached transcriptome-wide-significance (FDR < 5%). Gene-set-enrichment-analyses identified 2-upregulated pathways (MAPK signaling and phosphocholine biosynthesis) enriched at FDR < 25% in ER-negative tumors and normal-adjacent tissues, and both pathways have been previously reported to play key roles in ionizing radiation induced tumorigenesis in experimental settings. Conclusion Our findings provide insights into the molecular pathways of radon exposure that may influence breast cancer etiology.

show abstract

“…Cumulative evidence supports a causal role of alcohol intake and breast cancer incidence [2][3][4]. Potential mechanisms include both global and sitespecific changes induced by alcohol intake [5]. Nonetheless, evidence about alcohol consumption and breast cancer survival, an inherent element in cancer-related disease burden, has been mixed.…”

Section: Introductionmentioning

confidence: 99%

Breast cancer survival and the expression of genes related to alcohol drinking

Cheng

Gonzalez-Reymundez

et al. 2020

PLoS ONE

View full text Add to dashboard Cite

Breast cancer is the leading cause of cancer-related disease in women. Cumulative evidence supports a causal role of alcohol intake and breast cancer incidence. In this study, we explore the change on expression of genes involved in the biological pathways through which alcohol has been hypothesized to impact breast cancer risk, to shed new insights on possible mechanisms affecting the survival of breast cancer patients. Here, we performed differential expression analysis at individual genes and gene set levels, respectively, across survival and breast cancer subtype data. Information about postdiagnosis breast cancer survival was obtained from 1977 Caucasian female participants in the Molecular Taxonomy of Breast Cancer International Consortium. Expression of 16 genes that have been linked in the literature to the hypothesized alcohol-breast cancer pathways, were examined. We found that the expression of 9 out of 16 genes under study were associated with cancer survival within the first 4 years of diagnosis. Results from gene set analysis confirmed a significant differential expression of these genes as a whole too. Although alcohol consumption is not analyzed, nor available for this dataset, we believe that further study on these genes could provide important information for clinical recommendations about potential impact of alcohol drinking on breast cancer survival.

show abstract

Alcohol consumption and breast tumor gene expression

Cited by 23 publications

References 51 publications

PAM50 Molecular Intrinsic Subtypes in the Nurses' Health Study Cohorts

PAM50 Molecular Intrinsic Subtypes in the Nurses' Health Study Cohorts

Low dose environmental radon exposure and breast tumor gene expression

Breast cancer survival and the expression of genes related to alcohol drinking

Contact Info

Product

Resources

About