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Excited to share that our work “Inherited rare, deleterious variants in ATM increase lung adenocarcinoma risk” is now published in JTO: 1/7 @JTOonline
@SinaiGenetics @IcahnInstitute #lcsm https://pubmed.ncbi.nlm.nih.gov/32866655/ ">https://pubmed.ncbi.nlm.nih.gov/32866655/...
@SinaiGenetics @IcahnInstitute #lcsm https://pubmed.ncbi.nlm.nih.gov/32866655/ ">https://pubmed.ncbi.nlm.nih.gov/32866655/...
Our study aimed to identify inherited risk factors for lung adenocarcinoma (LUAD). This will enable better identification of high-risk individuals, who can then benefit from increased surveillance and early detection programs, there by improving their prognosis. 2/7
For this, we have analyzed by far the largest whole-exome sequencing case-control cohort of 1,083 patients and 7,650 controls through a rigorous analysis framework, and tested the burden of GERMLINE RARE DELETERIOUS VARIANTS (RDVs) in cases vs. controls 3/7
We discovered that rare, deleterious germline variants (RDVs) in ATM gene increased LUAD risk in two independent cohorts (combined cohort, OR=4.6, p=2e-4). Further, this replicated in a third independent cohort of 1,594 participants in #MSKImpact study. @sloan_kettering 4/7
Remarkably, we also discovered an ATM variant, rs56009889, that is more frequent in #AshkenaziJewish (AJ) cases vs. AJ controls in our cohort (OR =2.7, p=7e-03). As this variant is common in the AJ population, further evaluation is needed to assess its pathogenicity. 5/7
Overall, our results indicate ATM is a moderate LUAD risk gene. As ATM is a recognized risk gene for pancreas, breast & prostate cancers, LUAD may be part of ATM-related cancer syndrome. ATM RDV carriers can benefit from increased surveillance (low dose CT-scanning). 6/7
Finally, a big thank you to my mentors, collaborators and funders for this great study @ZeynepHG @Ken_Onel @MGZauderer @velculescu and few more not in twitter and @LUNGevity 7/7
