Impact of diverticular disease on prostate cancer risk among hypertensive men

Tomer, Nir; Chakravarty, Dimple; Ratnani, Parita; Mohamed, Nihal; Jambor, Ivan; Dovey, Zachary; Palese, Michael; Tewari, Ashutosh

doi:10.1038/s41391-021-00454-w

Cited by 3 publications

(1 citation statement)

References 33 publications

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“…The reasons behind the association of high DBP, rather than SBP, with systemic inflammation are yet to be elucidated [65]. It might be related to the substantial heterogeneity of prostate carcinogenesis, especially in its genetics [12, 66]. Despite inconsistent findings, BP levels are used in PrC prognosis [67] and are monitored in PrC patients, as a recent study suggested men with first-line palliative treatment had higher rates of ischaemic stroke and heart failure [68].…”

Section: Discussionmentioning

confidence: 99%

comorbidPGS: an R package assessing shared predisposition between Phenotypes using Polygenic Scores

Pascat,

Zudina,

Ulrich

et al. 2024

Hum Hered

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Introduction Polygenic Score (PGS) is a valuable method for assessing the estimated genetic liability to a given outcome or genetic variability contributing to a quantitative trait. While PRSs are widely used for complex traits, their application in uncovering shared genetic predisposition between phenotypes, i.e. when genetic variants influence more than one phenotype, remains limited. Methods We developed an R package, comorbidPGS, which facilitates a systematic evaluation of shared genetic effects among (cor)related phenotypes using PGSs. The comorbidPGS package takes as input a set of Single Nucleotide Polymorphisms (SNPs) along with their established effects on the original phenotype (Po), referred to as Po-PGS. It generates a comprehensive summary of effect(s) of Po-PGS on target phenotype(s) (Pt) with customisable graphical features. Results We applied comorbidPGS to investigate the shared genetic predisposition between phenotypes defining elevated blood pressure (Systolic Blood Pressure, SBP; Diastolic Blood Pressure, DBP; Pulse Pressure, PP) and several cancers (Breast Cancer, BrC; Pancreatic Cancer, PanC; Kidney Cancer, KidC; Prostate Cancer, PrC; Colorectal Cancer, CrC) using the European ancestry UK Biobank individuals and GWAS meta-analyses summary statistics from independent set of European ancestry individuals. We report a significant association between elevated DBP and the genetic risk of PrC (β (SE)=0.066 (0.017), P-value=9.64×10^(-5)), as well as between CrC PGS and both, lower SBP (β (SE)=-0.10 [0.029], P-value=3.83×10^(-4))) and lower DBP (β (SE)=-0.055 [0.017], P-value=1.05×10^(-3)). Our analysis highlights two nominally significant relationships for individuals with genetic predisposition to elevated SBP leading to higher risk of KidC (OR [95%CI]=1.04 [1.0039-1.087], P-value=2.82×10^(-2)) and PrC (OR [95%CI]=1.02 [1.003-1.041], P-value=2.22×10^(-2)). Conclusion Using comorbidPGS, we underscore mechanistic relationships between blood pressure regulation and susceptibility to three comorbid malignancies. This package offers valuable means to evaluate shared genetic susceptibility between (cor)related phenotypes through polygenic scores.

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Section: Discussionmentioning

confidence: 99%

comorbidPGS: an R package assessing shared predisposition between Phenotypes using Polygenic Scores

Pascat,

Zudina,

Ulrich

et al. 2024

Hum Hered

View full text Add to dashboard Cite

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Risk of Cancer in Patients With Diverticular Disease: A Population-Based Cohort Study

Troelsen,

Farkas,

Erichsen

et al. 2024

Clinical Gastroenterology and Hepatology

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Cancer risk in patients with diverticular disease: A nationwide cohort study

Walker

Thuresson

et al. 2022

JNCI: Journal of the National Cancer Institute

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BACKGROUND There are little data on diverticular disease and cancer development, other than colorectal cancer. METHODS We conducted a population-based, matched cohort study with linkage of nationwide registers to the ESPRESSO histopathology cohort. We included 75,704 patients with a diagnosis of diverticular disease and colorectal histopathology and 313,480 reference individuals from the general population matched on age, sex, calendar year, and county. Cox proportional hazards models estimated multivariable-adjusted hazard ratios (HRs) for associations between diverticular disease and overall cancer and specific cancers. RESULTS Over a median follow-up of 6 years, we documented 12,846 incident cancers among patients with diverticular disease and 43,354 incident cancers among reference individuals from the general population. Compared to reference individuals, patients with diverticular disease had significantly increased overall cancer incidence (24.5 vs. 18.1 per 1,000 person-years), equivalent to 1 extra cancer case in 16 individuals with diverticular disease followed for ten years. After adjusting for covariates, having a diagnosis of diverticular disease was associated with a 33% increased risk of overall cancer (95% confidence interval (CI)=1.31-1.36). The risk increases also persisted compared to siblings as secondary comparators (HR = 1.26; 95%CI = 1.21-1.32). Patients with diverticular disease also had increased risk of specific cancers, including colon cancer (HR = 1.71; 95%CI = 1.60-1.82), liver cancer (HR = 1.72; 95%CI = 1.41-2.10), pancreatic cancer (HR = 1.62; 95%CI = 1.42-1.84), and lung cancer (HR = 1.50; 95%CI = 1.39-1.61). The increase in colorectal cancer risk was primarily restricted to the first year of follow-up, and especially early cancer stages. CONCLUSIONS Patients with diverticular disease who have colorectal histopathology have an increased risk of overall incident cancer.

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Impact of diverticular disease on prostate cancer risk among hypertensive men

Cited by 3 publications

References 33 publications

comorbidPGS: an R package assessing shared predisposition between Phenotypes using Polygenic Scores

comorbidPGS: an R package assessing shared predisposition between Phenotypes using Polygenic Scores

Risk of Cancer in Patients With Diverticular Disease: A Population-Based Cohort Study

Cancer risk in patients with diverticular disease: A nationwide cohort study

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