Tumour DNA methylation markers associated with breast cancer survival: a replication study.

Background: Tumour DNA methylation has been investigated as a potential marker for breast cancer survival, but findings often lack replication across studies.

Methods: This study sought to replicate previously reported associations for individual CpG sites and multi-CpG signatures using an Australian sample of 425 women with breast cancer from the Melbourne Collaborative Cohort Study (MCCS). Candidate methylation sites (N = 22) and signatures (N = 3) potentially associated with breast cancer survival were identified from five prior studies that used The Cancer Genome Atlas (TCGA) methylation dataset, which shares key characteristics with the MCCS: comparable sample size, tissue type (formalin-fixed paraffin-embedded; FFPE), technology (Illumina HumanMethylation450 array), and participant characteristics (age, ancestry, and disease subtype and severity).

Polygenic score distribution differences across European ancestry populations: implications for breast cancer risk prediction.

Background: The 313-variant polygenic risk score (PRS) provides a promising tool for clinical breast cancer risk prediction. However, evaluation of the PRS across different European populations which could influence risk estimation has not been performed.

Methods: We explored the distribution of PRS across European populations using genotype data from 94,072 females without breast cancer diagnosis, of European-ancestry from 21 countries participating in the Breast Cancer Association Consortium (BCAC) and 223,316 females without breast cancer diagnosis from the UK Biobank.

Evaluation of agreement between common clustering strategies for DNA methylation-based subtyping of breast tumours.

Aims: Clustering algorithms have been widely applied to tumor DNA methylation datasets to define methylation-based cancer subtypes. This study aimed to evaluate the agreement between subtypes obtained from common clustering strategies.

Materials & Methods: We used tumor DNA methylation data from 409 women with breast cancer from the Melbourne Collaborative Cohort Study (MCCS) and 781 breast tumors from The Cancer Genome Atlas (TCGA).

Menopausal hormone therapy: assessing associations with breast and colorectal cancers by familial risk.

Menopausal users of hormone replacement therapy (HRT) are at increased breast cancer risk and decreased colorectal cancer (CRC) risk compared with individuals who have never used HRT, but these opposing associations may differ by familial risk of breast cancer and CRC. We harmonized data from 3 cohorts and generated separate breast cancer and CRC familial risk scores based on cancer family history. We defined moderate or strong family history as a risk score of 0.