Dataset Information

Unbalanced bidirectional causal association between thyroid cancer and ER-positive breast cancer: should we recommend screening for thyroid cancer in breast cancer patients?

ABSTRACT:

Background

The association between breast cancer (BC) and thyroid cancer (TC) has been studied in several epidemiological studies. However, the underlying causal relationship between them is not yet clear.

Methods

The data from the latest large-sample genome-wide association studies (GWAS) of BC and TC were searched in the public GWAS database. The BC GWAS data included estrogen receptor (ER)-positive and negative subgroups. Two-way two-sample Mendelian Randomization (MR) was used to explore the potential causal relationship between BC and TC. Inverse variance weighting (IVW) and the MR-Egger method were used to combine the estimation of each single nucleotide variation (previous single nucleotide polymorphism). BC was taken as the result, and the effect of TC exposure was analyzed. Then, the effect of BC exposure on the result of TC was analyzed.

Results

Both IVW and MR-Egger results indicated that gene-driven thyroid cancer does not cause estrogen receptor-positive breast cancer and is a protective factor (β = -1.203, SE = 4.663*10^-4, P = 0.010). However, gene-driven estrogen receptor-positive breast cancer can lead to the development of thyroid cancer (β = 0.516, SE = 0.220, P = 0.019).

Conclusion

From the perspective of gene drive, people with TC are less likely to have ER-positive BC. In contrast, people with ER-positive BC are more likely to have TC. Therefore, it is recommended that patients with BC be screened regularly for TC.

SUBMITTER: Wang H

PROVIDER: S-EPMC10712093 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature

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Publications

Unbalanced bidirectional causal association between thyroid cancer and ER-positive breast cancer: should we recommend screening for thyroid cancer in breast cancer patients?

Wang Hongtao H Li Shiwen S Shi Jinyuan J Feng Chuyao C Wang Yanan Y Zhang Fan F

BMC genomics 20231211 1

<h4>Background</h4>The association between breast cancer (BC) and thyroid cancer (TC) has been studied in several epidemiological studies. However, the underlying causal relationship between them is not yet clear.<h4>Methods</h4>The data from the latest large-sample genome-wide association studies (GWAS) of BC and TC were searched in the public GWAS database. The BC GWAS data included estrogen receptor (ER)-positive and negative subgroups. Two-way two-sample Mendelian Randomization (MR) was used ...[more]

PMID: 38082224

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Project description:ImportanceThere are insufficient data comparing 16α-18F-fluoro-17β-estradiol (FES) positron emission tomography (PET) computed tomography (CT) with standard-of-care imaging (SOC) for staging locally advanced breast cancer (LABC) or evaluating suspected recurrence.ObjectiveTo determine the detection rate of FES PET/CT and SOC for distant metastases in patients with estrogen receptor (ER)-positive LABC and recurrences in patients with ER-positive BC and suspected recurrence.Design, setting, and participantsThis diagnostic study was conducted as a single-center phase 2 trial, from January 2021 to September 2023. The study design provided 80% power to find a 20% detection rate difference. Participants included patients with ER-positive LABC (cohort 1) or suspected recurrence (cohort 2). Data were analyzed from September 2023 to February 2024.ExposureParticipants underwent both SOC imaging and experimental FES PET/CT. When there were suspicious lesions on imaging, 1 was biopsied for histopathological reference standard to confirm presence (true positive) or absence (false positive) of malignant neoplasm.Main outcomes and measuresThe outcome of interest was the detection rate of FES PET CT vs SOC for distant metastases and recurrences.ResultsA total of 124 patients were accrued, with 62 in cohort 1 (median [IQR] age, 52 [32-84] years) and 62 in cohort 2 (median [IQR] age, 66 [30-93] years). In cohort 1, of 14 true-positive findings, SOC imaging detected 12 and FES detected 11 (P > .99). In cohort 2, of 23 true-positive findings, SOC detected 16 and FES detected 18 (P = .77). In 30 patients with lobular histology, of 11 true-positive findings, SOC detected 5 and FES detected 9 (P = .29). There were 6 false-positive findings on SOC and 1 false-positive finding on FES PET/CT (P = .13).Conclusions and relevanceIn this diagnostic study with pathological findings as the reference standard, no difference was found between FES PET/CT and current SOC imaging for detecting distant metastases in patients with ER-positive LABC or recurrences in patients with ER-positive tumors and suspected recurrence. FES PET/CT could be considered for both clinical indications, which are not part of current Appropriate Use Criteria for FES PET. The findings regarding FES PET/CT in patients with lobular tumors, and for lower false positives than current SOC imaging, warrant further investigation.

Project description:BackgroundWhile recent integrative analyses of copy number and gene expression data in breast cancer have revealed a complex molecular landscape with multiple subtypes and many oncogenic/tumour suppressor driver events, much less is known about the role of DNA methylation in shaping breast cancer taxonomy and defining driver events.ResultsHere, we applied a powerful integrative network algorithm to matched DNA methylation and RNA-Seq data for 724 estrogen receptor (ER)-positive (ER+) breast cancers and 111 normal adjacent tissue specimens from The Cancer Genome Atlas (TCGA) project, in order to identify putative epigenetic driver events and to explore the resulting molecular taxonomy. This revealed the existence of nine functionally deregulated epigenetic hotspots encompassing a total of 146 genes, which we were able to validate in independent data sets encompassing over 1000 ER+ breast cancers. Integrative clustering of the matched messenger RNA (mRNA) and DNA methylation data over these genes resulted in only two clusters, which correlated very strongly with the luminal-A and luminal B subtypes. Overall, luminal-A and luminal-B breast cancers shared the same epigenetically deregulated hotspots but with luminal-B cancers exhibiting increased aberrant DNA methylation patterns relative to normal tissue. We show that increased levels of DNA methylation and mRNA expression deviation from the normal state define a marker of poor prognosis. Our data further implicates epigenetic silencing of WNT signalling antagonists and bone morphogenetic proteins (BMP) as key events underlying both luminal subtypes but specially of luminal-B breast cancer. Finally, we show that DNA methylation changes within the identified epigenetic interactome hotspots do not exhibit mutually exclusive patterns within the same cancer sample, instead exhibiting coordinated changes within the sample.ConclusionsOur results indicate that the integrative DNA methylation and transcriptomic landscape of ER+ breast cancer is surprisingly homogeneous, defining two main subtypes which strongly correlate with luminal-A/B subtype status. In particular, we identify WNT and BMP signalling as key epigenetically deregulated tumour suppressor pathways in luminal ER+ breast cancer, with increased deregulation seen in luminal-B breast cancer.

Dataset Information

Unbalanced bidirectional causal association between thyroid cancer and ER-positive breast cancer: should we recommend screening for thyroid cancer in breast cancer patients?

Background

Methods

Results

Conclusion

Publications

Unbalanced bidirectional causal association between thyroid cancer and ER-positive breast cancer: should we recommend screening for thyroid cancer in breast cancer patients?

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