Dairy consumption in adulthood has been demonstrated to influence cancer risk. Although childhood and adolescence represent critical periods of rapid growth, the relationship between milk intake in early life and later cancer risk is unclear. Thus, we examined this relationship by conducting a meta-analysis of the observational studies. PubMed and Embase were searched for relevant articles that were published throughout December 2021. The summary relative risk (RR) and 95% confidence interval (CI) were estimated using the DerSimonian-Laird random-effects model. The summary RR for the highest vs. lowest milk intake was 0.83 (95% CI = 0.69–1.00; p = 0.05; I² = 60%; seven studies) for breast cancer, 0.98 (95% CI = 0.72–1.32; p = 0.88; I² = 51%; four studies) for prostate cancer, and 0.90 (95% CI = 0.42–1.93; p = 0.78; I² = 83%; three studies) for colorectal cancer. No evidence of an association emerged in subgroup analyses of menopausal status, cancer stage, fat content of milk, life stage of milk intake, or study design. Consistent results were observed in the meta-analyses using total dairy intake. In conclusion, milk intake during childhood and adolescence might not be associated with risks of breast, prostate, and colorectal cancer later in life. Given the small number of studies that were included in our meta-analysis, and the high heterogeneity, more studies are warranted for a definitive conclusion.

Exhausted CD8 ⁺ T (Tex) cells comprise heterogeneous subsets with varying cytotoxic and dysfunctional properties, making inhibitory receptor profiles unreliable indicators of function. Therefore, it is essential to define transcriptional regulators or markers that accurately reflect these states. Here, we identified ETS variant 4 (ETV4) as a transcription factor that restricts cytotoxic Tex differentiation within tumors. ETV4 deficiency promotes the emergence of a CD74 ⁺ cytotoxic Tex subset while preserving the progenitor Tex (Tpex) pool. CD74 serves as both a marker and regulator, reinforcing Tpex features and enhancing Tex cytotoxicity. Mechanistically, ETV4 loss derepresses T-bet expression, thereby increasing IFNγ production that induces CD74 expression in a paracrine manner. Single-cell analyses across human cancers revealed that CD74 ⁺ Tex cells are enriched for proliferative and metabolic programs and correlate with improved survival. Collectively, we establish the ETV4–CD74 axis as a regulator of Tex fate and promising therapeutic target to augment anti-tumor immunity.

Background/Objectives: Communicating genetic risk has been proposed as a motivational tool for weight control, but evidence remains limited. Methods: We conducted a randomized controlled trial among 53 overweight or obese young adults in South Korea. Participants were randomized to receive either their obesity-related genetic results with tailored lifestyle recommendations (intervention, n = 27) or genetic results limited to beauty traits (control, n = 26). Body weight and body composition were measured at baseline, 6 months, and 18 months. Primary outcome was change in body weight; secondary outcomes included body fat mass, body fat percentage, and skeletal muscle mass. Analyses used general linear and mixed models. Exploratory analyses examined effects among participants carrying ≥2 risk alleles across FTO, MC4R, and BDNF. Results: Overall, body weight and composition changes did not differ significantly between groups at 6 or 18 months. In exploratory subgroup analysis conducted among participants with obesity-related genetic risk, body weight increased in the intervention group (model-adjusted mean change, 2.68 kg; 95% CI, 2.28 to 3.09) but decreased in the control group (model-adjusted mean change, −11.58 kg; 95% CI, −1.99 to −1.18) over 18 months. Among participants with obesity-related genetic risk in the intervention group, those who reported behavior changes after receiving their genetic test results experienced modest weight reductions over 6 months compared with non-changers. Conclusions: Disclosure of obesity-related genetic information with tailored advice did not improve weight outcomes overall, but may benefit a subset of genetically susceptible individuals. Larger trials are warranted.