Journal Watch

Resources crucial for lung cancer screening

A Veterans Health Administration project that provided resources for lung cancer screening programs increased the number of veterans screened, according to a study published in the September 2022 issue of the journal CHEST. The researchers found that the demonstration project centers screened about 18 veterans per 1,000 eligible veterans per month, compared to 0.3 veterans screened in the comparison group. One-year follow-up screening also increased more rapidly at demonstration project medical centers, and follow-up screening was maintained following the project. Gains for screening unique veterans were not maintained after the project ended. The findings have already been used to advocate for a Department of Veterans Affairs National Lung Cancer Screening Program Office.

Pathways revealed for aggressive prostate cancer subtype  

Cribriform prostate cancer is an aggressive subtype of the disease characterized by its histology, but little is known about its molecular pathways. Research conducted in the lab of Paula Hurley, PhD, associate professor of Medicine and Urology, that was published Oct. 13, 2022, in Nature Communications has revealed new information about these pathways, including potential therapies. The upregulation of MYC-induced genes as well as the role of the NF- kappa B gene via the TNF alpha signaling pathway were associated with cribriform prostate cancer. Several molecules were also observed, including some that have implications for therapeutic opportunities.

New approach outperforms existing cancer susceptibility models

Investigators at Vanderbilt led by Xingyi Guo, PhD, associate professor of Medicine in the Division of Epidemiology, and at the University of Calgary have devised a new approach for conducting gene-based analyses for cancer susceptibility that outperforms existing models. Their research, published online Nov. 19, 2022, in Nature Communications, tested a new model for transcriptome-wide association studies (TWAS), a gene-based method for investigating susceptibility to cancer and other complex diseases. The researchers integrated transcription factors, which are the proteins involved in the process of gene regulation, into a new model called sTF-TWAS. The new approach detected more genes than those from existing TWAS models. 

Study raises concerns about hereditary breast cancer overtreatment 

Women with inherited mutations in breast cancer genes have lifetime varying breast cancer risks, ranging from high to moderate risk genes. Per national practice guidelines, risk-reducing bilateral mastectomy is a consideration for patients with inherited mutations in high- but not moderate-penetrance risk genes. Tuya Pal, MD, and colleagues found similar rates of bilateral mastectomy across high- and moderate-penetrance genes. The findings, published in JAMA Oncology, raise concerns about possible overtreatment for patients with variants in moderate-penetrance genes. 

Study finds inherited link to appendix cancer

One of every 10 patients with appendiceal cancer carries a germline genetic variant associated with cancer predisposition, according to a study in JAMA Oncology that is the first to show inherited risk factors for this rare cancer. Historically, it has been thought that appendiceal cancer is not hereditary, but its rarity has presented challenges for understanding the characteristics of the disease and developing therapies. A research team led by Andreana Holowatyj, PhD, MSCI, assistant professor of Medicine and Cancer Biology, analyzed multigene panel testing data from a nationwide clinical testing laboratory in the U.S. for a total of 131 patients with appendiceal cancer. They found that 11.5% of patients had at least one germline genetic variant in a cancer susceptibility gene. In addition, among the subset of patients with appendix cancer as the first and only primary tumor, they observed a similar prevalence (10.8%), further linking a familial component to this disease.

Study sheds light on blood cancer progression

Approximately one-third of patients diagnosed with the blood disorder myelodysplastic syndrome (MDS) will progress to secondary acute myeloid leukemia (sAML), a blood cancer. P. Brent Ferrell, MD, and colleagues are using single-cell techniques to explore the accumulation of mutations — clonal evolution — during the progression from MDS to sAML. The findings, reported in Blood Cancer Discovery, define serial changes in MDS that have clinical and therapeutic implications. The researchers suggest that analysis of larger data sets could identify specific therapeutic targets, with the hope of identifying strategies for preventing leukemic progression before it occurs.