Editors’ Selections from Relevant Scientific Publications

Aging-dependent differential gene expression (by Yan et al via Cancer Cell)The likelihood of developing breast cancer increases considerably for older individuals, but the biological basis for this heightened risk remains unclear. Yan and colleagues conducted an extensive single-cell multi-omic analysis to identify molecular factors associated with age-related changes in rat breast tissue. They observed notable upregulation of a growth factor called midkine in older animals, showing that midkine induced aging-associated changes in gene expression and increased proliferation in mammary epithelial cells. Treatment with midkine also promoted tumor formation in a rat breast cancer model. Similar patterns of age-related midkine expression were observed in human blood and breast tissue, and elevated levels of this protein were predictive of both higher cancer risk and poorer prognosis in younger women, highlighting midkine’s potential utility as a clinical biomarker or even a target for preventative treatment.Yan P, … Polyak K. Cancer Cell. 2024 Sep 26:S1535-6108(24)00350-7.Bacteria from mouth (by Magdalena Wiklund via Flickr)A new study investigated the impact of oral bacterial and fungal microbiomes on the risk of head and neck squamous cell cancer (HNSCC). Using a prospective case-control study of 3 large cohorts including 236 incident cases of HNSCC, Kwak and colleagues found 13 novel oral bacterial species, such as Prevotella salivae, Streptococcus sanguinis, Leptotrichia species and Proteobacteria species, associated with increased HNSCC risk. The researchers observed an association with bacteria related to periodontal disease, indicating that poor oral health may increase HNSCC risk. In contrast, no oral fungi were associated with increased HNSCC risk. Overall, these findings suggest that a potential role for bacteria markers in identifying individuals at elevated risk for HNSCC, which could inform future screening strategies.Kwak S, … Hayes RB. JAMA Oncol. 2024 Sep 26.Hormonal contraception (by Austin & Zak via Flickr)This study assessed the effect of hormonal contraception on the risk of developing breast cancer (BC) in women with germline mutations in BRCA1 and BRCA2. Phillips and colleagues analyzed data from 3,882 BRCA1 and 1,509 BRCA2 mutation carriers who reported use of hormonal contraceptives for at least 1 year. Among BRCA1 mutation carriers, use of hormonal contraceptives for at least one year was associated with an average 29% increased relative risk of BC compared to those who never used, with risk increasing proportionally by 3% for each additional year of use. However, BC risk was not associated with younger age at first use or use before first birth. In contrast, no increased risk of BC was observed in BRCA2 mutation carriers associated with use of hormonal contraceptives. These findings suggest that hormonal contraceptive use in women with BRCA1 mutations warrants careful individual risk assessment and monitoring.Phillips KA, … Milne RL. J Clin Oncol. 2024 Oct 2:JCO2400176.Prostate biopsy (by Cancer Research UK uploader via Wikimedia Commons)Systematic biopsy in men with elevated prostate-specific antigen is an effective strategy for early detection of prostate cancer, but often leads to overtreatment of low-risk lesions. Hugosson and colleagues performed a clinical study of more than 13,000 men to evaluate whether targeted biopsy guided by magnetic resonance imaging (MRI) offers a better alternative. They found that men in the MRI cohort were 51% less likely to receive clinically-insignificant diagnoses, thus avoiding unnecessary interventions. Importantly, this more selective MRI-guided approach did not meaningfully increase the likelihood of missing high-risk lesions with metastatic potential relative to systematic biopsy. The cost of expanding MRI screening may be high initially, but the authors also see opportunities to substantially reduce healthcare utilization while still achieving effective prevention.Hugosson J, … Hellstrom M. N Engl J Med. 2024 Sep 26;391(12):1083–1095.