Bradley et al. Page 525

Metformin is widely used in the management of type 2 diabetes mellitus. Epidemiologic studies have reported strong inverse associations between metformin use and risk of several cancers, including colorectal (CRC). Concern that time-related biases, such as immortal time bias, were influencing reported associations led Bradley and colleagues to re-examine metformin and CRC risk using methods to minimize these biases. Specifically, the authors accounted for time-varying exposure to metformin and other diabetes medications and adjusted for diabetes duration. Despite applying more rigorous methods, the authors observed an inverse association between long-term metformin use and CRC risk that appeared to be restricted to men.

Assi et al. Page 531

Hepatocellular carcinoma (HCC) incidence is rising in regions where established HCC risk factors are not predominant. The rise is likely due to factors such as obesity and unhealthy lifestyle exposures. This study, by Assi and colleagues, presents an analytical framework to explore exposure-specific metabolic signatures and assess their mediating role in the association between various lifestyle behaviors and HCC risk using detailed metabolomic and lifestyle data from a large prospective cohort. Metabolic profiles of obesity, smoking, and alcohol intake mediated HCC carcinogenesis. These findings contribute to further understanding of HCC etiology, thus strengthening public health advice for cancer prevention by modifying unhealthy lifestyle behaviors.

Boen et al. Page 541

Using novel questionnaire, biomarker, and vital records data, this study by Boen and colleagues examines how diverse measures of social support relate to mortality risk among individuals with cancer as well as the mediating role of inflammation as a biological mechanism. Findings revealed that cancer patients reporting less social support satisfaction had higher mortality risk than those reporting greater satisfaction, partly due to the elevated risk of inflammation associated with low satisfaction. The study offers new insights for intervention efforts aimed at promoting meaningful social connections as a means for improving cancer survival.

Sponholtz et al. Page 558

Endometrial cancer incidence has been increasing among black women. Despite established roles of estrogens and progestins in endometrial cancer etiology, few studies have investigated the influence of exogenous hormone use among black women. Similar to prior findings, the Black Women's Health Study found that oral contraceptive use was associated with reduced endometrial cancer risk; estrogen-only menopausal hormone use was associated with increased risk. Also consistent with previous studies, the protective effects of oral contraceptive use were weaker among obese women. The results of this study by Sponholzt and colleagues suggest that the high obesity prevalence among black women may contribute to their increasing endometrial cancer incidence by mitigating the beneficial effects of oral contraceptive use.