Dataset Information

Second primary cancer after female breast cancer: Familial risks and cause of death.

ABSTRACT:

Background

With continuous increases in survival rates following breast cancer (BC) diagnosis, the challenge of multiple primary cancers has become an issue. The data on familial risk of SPCs after BC diagnosis and the related mortality in BC patients are scarce.

Methods

A total of 87 752 female BC patients were followed for SPC diagnoses and records of death. Relative risks (RRs) of SPC in BC patients who had first-degree relatives (parents or siblings) affected by the same cancer were compared to the patients without family history. Causes of death were compared between patients with and without SPC.

Results

After a median follow-up of 5 years, 14 952 BC patients developed SPCs, among which 10 280 (68.8%) had first-degree relatives diagnosed with cancer. Familial risks were significant for 14 site-specific SPCs, and the highest risk was for second ovarian cancer (RR = 6.28, 95%CI: 4.50-8.75), compared to those without family history (1.49, 1.34-1.65). In patients with SPC, SPC was the main cause of death, including diverse cancers and BC in approximately equal proportions.

Conclusions

Family history contributed to the excess number of patients with SPCs, and SPC was the leading cause of death in patients with SPC. Taking family history at diagnosis of BC may provide warning signs with regard to possible subsequent SPCs and may offer possibilities for counseling, intervention and management.

SUBMITTER: Zheng G

PROVIDER: S-EPMC6346247 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Second primary cancer after female breast cancer: Familial risks and cause of death.

Zheng Guoqiao G Hemminki Akseli A Försti Asta A Sundquist Jan J Sundquist Kristina K Hemminki Kari K

Cancer medicine 20181126 1

<h4>Background</h4>With continuous increases in survival rates following breast cancer (BC) diagnosis, the challenge of multiple primary cancers has become an issue. The data on familial risk of SPCs after BC diagnosis and the related mortality in BC patients are scarce.<h4>Methods</h4>A total of 87 752 female BC patients were followed for SPC diagnoses and records of death. Relative risks (RRs) of SPC in BC patients who had first-degree relatives (parents or siblings) affected by the same cance ...[more]

PMID: 30479046

Similar Datasets

Project description:In total, ~25% of familial breast cancer (BC) is attributed to germline mutations of the BRCA1 and BRCA2 genes, while the rest of the cases are included in the BRCAX group. BC is also known to affect men, with a worldwide incidence of 1%. Epigenetic alterations, including DNA methylation, have been rarely studied in male breast cancer (MBC) on a genome-wide level. The aim of the present study was to examine the global DNA methylation profiles of patients with BC to identify differences between familial female breast cancer (FBC) and MBC, and according to BRCA1, BRCA2 or BRCAX mutation status. The genomic DNA of formalin-fixed paraffin-embedded tissues from 17 women and 7 men with BC was subjected to methylated DNA immunoprecipitation and hybridized on human promoter microarrays. The comparison between FBC and MBC revealed 2,846 significant differentially methylated regions corresponding to 2,486 annotated genes. Gene Ontology enrichment analysis revealed molecular function terms, such as the GTPase superfamily genes (particularly the GTPase Rho GAP/GEF and GTPase RAB), and cellular component terms associated with cytoskeletal architecture, such as 'cytoskeletal part', 'keratin filament' and 'intermediate filament'. When only FBC was considered, several cancer-associated pathways were among the most enriched KEGG pathways of differentially methylated genes when the BRCA2 group was compared with the BRCAX or BRCA1+BRCAX groups. The comparison between the BRCA1 and BRCA2+BRCAX groups comprised the molecular function term 'cytoskeletal protein binding'. Finally, the functional annotation of differentially methylated genes between the BRCAX and BRCA1+BRCA2 groups indicated that the most enriched molecular function terms were associated with GTPase activity. In conclusion, to the best of our knowledge, the present study was the first to compare the global DNA methylation profile of familial FBC and MBC. The results may provide useful insights into the epigenomic subtyping of BC and shed light on a possible novel molecular mechanism underlying BC carcinogenesis.

Project description:PurposeA special association between breast cancer and second primary lung cancer in Taiwanese women has been discovered not only in clinical practice, but also in a large population-based study. We hereby investigate the association between breast cancer and second primary lung cancer in Taiwanese women.MethodsThis study was conducted from the National Health Insurance Research Database (NHIRD) from Taiwan National Health Insurance (NHI). Patients older than 18 years old and hospitalized with a first diagnosis of breast cancer during 2000 to 2012 were enrolled in the breast cancer group. Patients who were cancer free were frequency-matched with the breast cancer group by age (every five-year span) and index year. The ratio of breast cancer group to non-breast cancer group was 1:4. The event as the outcome in this study was lung cancer. The comorbidities viewed as important confounding factors included coronary artery disease, stroke, hypertension, diabetes, chronic obstructive pulmonary disease, hyperlipidemia, tuberculosis, chronic kidney disease, and chronic liver disease and cirrhosis. We estimated the hazard ratios (HRs), adjusted hazard ratios (aHRs), and 95% confidence intervals (CIs) for risk of lung cancer in the breast cancer group and non-breast cancer group using Cox proportional hazard models. Sensitivity analysis was also done using propensity score matching. All of the statistical analyses were performed using SAS statistical software, version 9.4 (SAS Institute Inc., Cary, NC).ResultsThere were 94,451 breast cancer patients in the breast cancer group and 377,804 patients in the non-breast cancer group in this study. After being stratified by age, urbanization level, and comorbidities, the patients with breast cancer had a significantly higher risk of lung cancer compared with the patients without breast cancer, particularly for those who aged between 20 and 49 years (aHR = 2.10, 95% CI = 1.71-2.58), 50 and 64 years (aHR = 1.35, 95% CI = 1.15-1.58), and those without any comorbidities (aHR = 1.92, 95% CI = 1.64-2.23).ConclusionPatients with breast cancer had a significantly higher risk of developing second primary lung cancer compared with patients without breast cancer, particularly in younger groups and in those without any comorbidities. The special association may be attributed to some potential risk factors such as genetic susceptibility and long-term exposure to PM2.5, and is supposed to increase public awareness. Further studies are necessary given the fact that inherited genotypes, different subtypes of breast cancer and lung cancer, and other unrecognized etiologies may play vital roles in both cancers' development.

Project description:About 25% of familial breast cancer (BC) is attributed to germline mutations of BRCA1 and BRCA2 genes while the rest of patients are included in the BRCAX group. BC also affects men with a worldwide incidence of 1%. The epigenetic alterations, including those DNA methylation, have been rarely studied in the male breast cancer (MBC) on a genome-wide level. The aim of the current work was to study the global DNA methylation profiles of BC patients to look for differences between familial female breast cancer (FBC) and MBC and according to BRCA1, BRCA2 and BRCAX mutation status. The genomic DNA from FFPE tissues of 17 female and 7 male patients with BC was subjected to methylated DNA immunoprecipitation (MeDIP) and hybridized on human promoter microarrays. The comparison between FBC and MBC showed 2846 differentially methylated regions (DMRs) corresponding to 2486 distinct annotated genes. The gene ontology enrichment analysis revealdrelevant molecular function terms such as the GTPase superfamily genes (in particular the GTPase Rho GAP/GEF and GTPase RAB) and cellular component terms associated to cytoskeletal architecture such as “cytoskeletal part”, “keratin filament”, “intermediate filament". By considering only FBC, several cancer-associated pathways were the most enriched KEGG pathways of differentially methylated genes between BRCA2 and BRCAX or BRCA1+BRCAX groups. The comparison between BRCA1 group vs BRCA2+BRCAX group displayed the enriched molecular function term “cytoskeletal protein binding”. Finally, the functional annotation of differentially methylated genes between BRCAX and BRCA1+BRCA2 groups indicated that the most enriched molecular function terms were related to GTPase activity. In summary, this is the first study that compares the global DNA methylation profile of familial FBC and MBC and the results may provide useful insights into the epigenomic subtyping of breast cancer and shed light on a possible new molecular mechanisms underlying BC carcinogenesis.

Dataset Information

Second primary cancer after female breast cancer: Familial risks and cause of death.

Background

Methods

Results

Conclusions

Publications

Second primary cancer after female breast cancer: Familial risks and cause of death.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets