Dataset Information

DNA methylation at quantitative trait loci (mQTLs) varies with cell type and nonheritable factors and may improve breast cancer risk assessment.

ABSTRACT: To individualise breast cancer (BC) prevention, markers to follow a person's changing environment and health extending beyond static genetic risk scores are required. Here, we analysed cervical and breast DNA methylation (n = 1848) and single nucleotide polymorphisms (n = 1442) and demonstrate that a linear combination of methylation levels at 104 BC-associated methylation quantitative trait loci (mQTL) CpGs, termed the WID™-qtBC index, can identify women with breast cancer in hormone-sensitive tissues (AUC = 0.71 [95% CI: 0.65-0.77] in cervical samples). Women in the highest combined risk group (high polygenic risk score and WID™-qtBC) had a 9.6-fold increased risk for BC [95% CI: 4.7-21] compared to the low-risk group and tended to present at more advanced stages. Importantly, the WID™-qtBC is influenced by non-genetic BC risk factors, including age and body mass index, and can be modified by a preventive pharmacological intervention, indicating an interaction between genome and environment recorded at the level of the epigenome. Our findings indicate that methylation levels at mQTLs in relevant surrogate tissues could enable integration of heritable and non-heritable factors for improved disease risk stratification.

SUBMITTER: Herzog C

PROVIDER: S-EPMC10533818 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature

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DNA methylation at quantitative trait loci (mQTLs) varies with cell type and nonheritable factors and may improve breast cancer risk assessment.

Herzog Chiara C Jones Allison A Evans Iona I Zikan Michal M Cibula David D Harbeck Nadia N Colombo Nicoletta N Rådestad Angelique Flöter AF Gemzell-Danielsson Kristina K Pashayan Nora N Widschwendter Martin M

NPJ precision oncology 20230927 1

To individualise breast cancer (BC) prevention, markers to follow a person's changing environment and health extending beyond static genetic risk scores are required. Here, we analysed cervical and breast DNA methylation (n = 1848) and single nucleotide polymorphisms (n = 1442) and demonstrate that a linear combination of methylation levels at 104 BC-associated methylation quantitative trait loci (mQTL) CpGs, termed the WID™-qtBC index, can identify women with breast cancer in hormone-sensitive ...[more]

PMID: 37758816

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Project description:Genetic dissection of the S rat genome has provided strong evidence for the presence of two interacting blood pressure (BP) quantitative trait loci (QTLs), termed QTL1 and QTL2, on rat chromosome 5. However, the identities of the underlying interacting genetic factors remain unknown. Further experiments targeted to identify the interacting genetic factors by the substitution mapping approach alone are difficult because of the interdependency of natural recombinations to occur at the two QTLs. We hypothesized that the interacting genetic factors underlying these two QTLs may interact at the level of gene transcription and thereby represent expression QTLs (eQTLs). To detect these interacting eQTLs, a custom QTL chip containing the annotated genes within QTL1 and QTL2 was developed and used to conduct a transcriptional profiling study of S and two congenic strains that retain either one or both the QTLs. The results uncovered an interaction between two transcription factors, DMRTA2 and NFIA. Further, the âbiological signatureâ elicited by these two transcription factors was differential between the congenic strain that retained LEW alleles at both QTL1 and 2 compared to the congenic strain that retained LEW alleles at QTL1 alone. A network of transcription factors potentially affecting BP could be traced, lending support to our hypothesis. Pairs of Cy5 and Cy3 labeled targets were co-hybridized onto either a custom long oligonucleotide microarray for the interrogation of 231 genes encompassed by QTL1 and QTL2, or a TIGR rat cDNA array consisting of 26,401 probe elements representing 20,465 unique non-QTL genes. A âflip-dyeâ or âbalanced blockâ design was used as the experimental method of choice to account for potential dye-bias labeling effects. Six âbalanced blockâ normalized files are submitted for the long oligonucleotide array interrogating the hearts from S versus S.LEW(5)x6x9 animals, fourteen âflip-dyeâ hybridizations are submitted for the cDNA array interrogating the hearts from S versus S.LEW(5)x6x9 animals, and twelve âflip-dyeâ hybridizations are submitted for the cDNA array interrogating the hearts from S versus S.LEW(5)x6x11 animals. GPR and MEV files cannot be located.

Dataset Information

DNA methylation at quantitative trait loci (mQTLs) varies with cell type and nonheritable factors and may improve breast cancer risk assessment.

Publications

DNA methylation at quantitative trait loci (mQTLs) varies with cell type and nonheritable factors and may improve breast cancer risk assessment.

Similar Datasets

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