A Polygenic Risk Score for Idiopathic Pulmonary Fibrosis and Interstitial Lung Abnormalities

Expression of HOXB7 in the Lung of Patients with Idiopathic Pulmonary Fibrosis: A Proof-of-Concept Study

“…Hoxb7 , a member of the homeobox gene family, has been demonstrated to play a crucial role in regulating proliferation, motility, and angiogenesis in various solid and non-solid neoplastic diseases, including leukemia [ 7 ], melanoma [ 8 ], breast [ 9 , 10 ], colorectal [ 11 ], head and neck [ 12 ], pancreatic [ 13 ], oral [ 14 ], and lung cancer (LC). LC has been frequently observed in IPF, particularly in current smoking patients exhibiting a rapid decline in forced vital capacity (FVC) [ 15 , 16 ]. For this purpose, several recent studies have identified common molecular pathways between IPF and lung cancer whose better knowledge could result in novel therapeutic strategies and optimal management of patients with both diseases.…”

When the Third Time Is Not the Charm—Trial Outcomes in Idiopathic Pulmonary Fibrosis

“…Stratifying for telomere length, genetic variations, polymorphisms (ie, MUC5B and TOLLIP), or even for individuals with different quantiles of an IPF polygenic risk score could identify subgroups that might be more likely to respond. 16 For example, there is evidence that patients with MUC5B (rs35705950) variant T allele genotypes experience increased survival during treatment with antifibrotic agents compared with those with the homozygous GG genotype. 17 Genetics is only one example of a biomarker of disease heterogeneity that can identify individuals who will respond to drugs.…”

“…The ongoing PRECISIONS trial (NCT04300920) is randomizing patients with IPF to N-acetylcysteine or placebo based on the TOLLIP variant genotype. Stratifying for telomere length, genetic variations, polymorphisms (ie, MUC5B and TOLLIP ), or even for individuals with different quantiles of an IPF polygenic risk score could identify subgroups that might be more likely to respond . For example, there is evidence that patients with MUC5B (rs35705950) variant T allele genotypes experience increased survival during treatment with antifibrotic agents compared with those with the homozygous GG genotype .…”

PRS-ing Forward to Identify Genetic Risk in Idiopathic Pulmonary Fibrosis

“…A new study by Moll and colleagues in this issue of the Journal (pp. 791–801 ) is the first comprehensive investigation of this method in IPF ( 8 ). The investigators analyzed data from 14,650 study participants, including 1,970 individuals with IPF and 1,068 individuals with interstitial lung abnormalities (ILAs), from a variety of cohorts to develop PRSs for IPF with or without inclusion of the MUC5B risk allele.…”