Incidence and risk of cancer among multiple sclerosis patients: A matched population‐based cohort study

Bosco‐Lévy, Pauline; Foch, Caroline; Grelaud, Angela; Sabidó, Meritxell; Lacueille, Clémentine; Jové, Jérémy; Boutmy, Emmanuelle; Blin, Patrick

doi:10.1111/ene.15226

Cited by 22 publications

(30 citation statements)

References 33 publications

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“…We found that the highest enrichment of SNPs is for GWAS in PrCa and Multiple Sclerosis (Table S6). Interestingly, a possible direct co-morbidity between multiple sclerosis and PrCa has been previously reported 25,26 .…”

Section: Protein Network Of Prca Risk-associated Regulatory Elementsmentioning

confidence: 87%

Reconstructing protein interactions at enhancer-promoter regions in prostate cancer

Armaos

Serra

Núñez-Carpintero

et al. 2022

Preprint

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DNA-binding proteins (DBPs) and in particular transcription factors interact with enhancers and their target genes through enhancer-promoter (E-P) interactions. Technological advancements such as chromosome conformation capture allow to identify E-P interactions, but the protein networks involved have not yet been characterized. Most importantly, the role of nuclear protein networks in human diseases has been so far poorly investigated. Prostate cancer (PrCa) heritability is associated with variations in enhancers that affect specific gene expression. Here, we introduce a novel approach, called Promoter-ENhancer-GUided Interaction Networks (PENGUIN), to identify protein-protein interactions (PPI) in E-P interactions and apply it to our PrCa dataset. PENGUIN integrates chromatin interactions between a promoter and its enhancers defined by high-coverage H3K27ac-HiChIP data, with a tissue-specific PPI network inferred from DNA-binding motifs and refined with gene expression. Among a total of 4,314 E-P networks, PENGUIN performed unsupervised clustering. We functionally validated this clustering procedure by searching for enrichments of specific biological features. We confirmed PENGUIN structural classification of E-P networks by showing a clear differential enrichment of the architectural protein CTCF. Next, and directly related to our PrCa case study, we observed that one of our 8 main clusters, containing 273 promoters, is particularly enriched for PrCA associated single nucleotide polymorphisms (SNPs) and oncogenes. Our approach proposes a mechanistic explanation for 208 PrCa SNPs falling either inside the binding sites of DNA-binding proteins (DBPs) or within genes encoding for intermediate proteins bridging E-P contacts. PENGUIN not only confirmed the relevance of key regulators in PrCa, but also identified new candidates for intervention, opening up new directions to identify molecular targets for disease treatment.

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Section: Protein Network Of Prca Risk-associated Regulatory Elementsmentioning

confidence: 87%

Reconstructing protein interactions at enhancer-promoter regions in prostate cancer

Armaos

Serra

Núñez-Carpintero

et al. 2022

Preprint

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“…Notably, a study published in Cancer Hematology Review in 2016 also reported MS is associated with the reduction of PCa risk ( 21 ), while a cohort study in 2020 summing up more than 6,800 patients showed that during an average follow-up of 65 years, MS was not associated with PCa risk. However, a recent cohort study in 2022 found that MS increased the risk of PCa ( 10 ).…”

Section: Discussionmentioning

confidence: 99%

“…The main characteristics of the included studies are summarized in Table I. These studies included seven cohorts studies (10)(11)(12)(15)(16)(17)(18) and one case-control study (19), summing 210,943 patients with MS. A total of two studies (16,17) from Sweden, two (11,12) from Canada, one (15) from Denmark, one (18) from Norway, one (19) from Finland and one (10) from France were included. Among these studies included in the meta-analysis, three studies were of high quality, and five were of moderate quality.…”

Section: Study Characteristics and Methodological Qualitymentioning

confidence: 99%

“…Results on the association between MS and PCa are conflicting. For instance, Bosco-Lévy et al ( 10 ) suggested that MS was associated with an increased risk of PCa [hazard ratio (HR)=2.08; 95% CI: 1.68-2.58], while Kingwell et al ( 11 ) showed that MS was not associated with the risk of PCa [standardized incidence ratio (SIR)=0.91; 95% CI: 0.64-1.27]. Marrie et al ( 12 ) showed different results.…”

Section: Introductionmentioning

confidence: 99%

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Association between multiple sclerosis and prostate cancer risk: A systematic review and meta‑analysis

Wang

et al. 2023

Oncol Lett

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Prostate cancer (PCa) risk in patients with multiple sclerosis (MS) remains to be elucidated. The present study conducted a meta-analysis to assess the relationship between MS and PCa. PubMed, EMBASE, Web of Science, and Cochrane Library databases were searched to identify studies on the PCa risk in patients with MS up to September 2022. A random effects meta-analyses model was performed to estimate the relative risk (RR) and the 95% confidence intervals (CI). All eight studies involving 210,943 patients with MS were identified and included in the meta-analysis. The present study revealed that there was no significant association between MS and the risk of PCa (RR=0.78, 95% CI: 0.56-1.08, P<0.0001). Subgroup analyses verified this conclusion when stratified by regions. However, after adjusting for potential confounders, the findings suggested conflicting results. The current evidence shows that compared with the population control, patients with MS have no relationship with PCa risk and further large samples and long-term trials are needed to verify these results.

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“…3 Epidemiological studies have yielded concerning observations. While it is unclear if breast cancer incidence is greater in women with MS, [4][5][6][7][8] they face a worse prognosis with a 28% increased hazard for all-cause mortality than the general population. 9 This raises the question of whether use of immunomodulatory disease modifying therapy (DMT) for MS increases cancer risk or worsens prognosis.…”

Section: Introductionmentioning

confidence: 99%

Clinical course of multiple sclerosis and patient experiences during breast cancer treatment

et al. 2023

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Background: Over one-third of multiple sclerosis (MS) patients are post-menopausal women, the primary demographic affected by breast cancer. After breast cancer diagnosis, there is little information about patients’ clinical experiences with both diseases. Objective: Utilize a case series of MS patients diagnosed with breast cancer to characterize oncologic and MS trajectories, and generate novel insights about clinical considerations using qualitative analysis. Methods: A single-center retrospective review was performed on medical record data of patients with MS and breast cancer. Thematic analysis was used to characterize experiences with the concurrent diagnoses. Results: For the 43 patients identified, mean age was 56.7 years at cancer diagnosis and MS duration was 16.5 years. Approximately half were treated with MS disease modifying therapy at cancer diagnosis, and half of these subsequently discontinued or changed therapy. Altogether 14% experienced MS relapse(s) during follow-up (with 2 relapses in the first 2 years), with mean annualized relapse rate of 0.03. Cohort Expanded Disability Status Scale (EDSS) scores remained stable during follow-up. Qualitative insights unique to this population were identified regarding immunosuppression use and neurologic symptoms. Conclusions: MS relapses were infrequent, and there was modest progression during breast cancer treatment. Oncologic outcomes were comparable to non-MS patients with similarly staged cancer.

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Incidence and risk of cancer among multiple sclerosis patients: A matched population‐based cohort study

Cited by 22 publications

References 33 publications

Reconstructing protein interactions at enhancer-promoter regions in prostate cancer

Reconstructing protein interactions at enhancer-promoter regions in prostate cancer

Association between multiple sclerosis and prostate cancer risk: A systematic review and meta‑analysis

Clinical course of multiple sclerosis and patient experiences during breast cancer treatment

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