Associations between circulating proteins and risk of breast cancer by intrinsic subtypes: a Mendelian randomisation analysis.

BACKGROUND: The aetiologic role of circulating proteins in the development of breast cancer subtypes is not clear. We aimed to examine the potential causal effects of circulating proteins on the risk of breast cancer by intrinsic-like subtypes within the Mendelian randomisation (MR) framework. METHODS: MR was performed using summary statistics from two sources: the INTERVAL protein quantitative trait loci (pQTL) Study (1890 circulating proteins and 3301 healthy individuals) and the Breast Cancer Association Consortium (BCAC; 106,278 invasive cases and 91,477 controls). The inverse-variance (IVW)-weighted method was used as the main analysis to evaluate the associations between genetically predicted proteins and the risk of five different intrinsic-like breast cancer subtypes and the weighted median MR method, the Egger regression, the MR-PRESSO, and the MRLocus method were performed as secondary analysis. RESULTS: We identified 98 unique proteins significantly associated with the risk of one or more subtypes (Benjamini-Hochberg false discovery rate < 0.05). Among them, 51 were potentially specific to luminal A-like subtype, 14 to luminal B/Her2-negative-like, 11 to triple negative, 3 to luminal B-like, and 2 to Her2-enriched-like breast cancer (ntotal = 81). Associations for three proteins (ICAM1, PLA2R1 and TXNDC12) showed evident heterogeneity across the subtypes. For example, higher levels of genetically predicted ICAM1 (per unit of increase) were associated with an increased risk of luminal B/HER2-negative-like cancer (OR = 1.06, 95% CI = 1.03-1.08, BH-FDR = 2.43 × 10-4) while inversely associated with triple-negative breast cancer with borderline significance (OR = 0.97, 95% CI = 0.95-0.99, BH-FDR = 0.065, Pheterogeneity < 0.005). CONCLUSIONS: Our study found potential causal associations with the risk of subtypes of breast cancer for 98 proteins. Associations of ICAM1, PLA2R1 and TXNDC12 varied substantially across the subtypes. The identified proteins may partly explain the heterogeneity in the aetiology of distinct subtypes of breast cancer and facilitate the personalised risk assessment of the malignancy.

Loneliness in the college student population: Prevalence and associations with substance use outcomes.

Objectives: We assessed the prevalence of loneliness by gender and gender-specific associations between loneliness and substance use in university students. Participants: Participants were students enrolled in colleges and universities throughout the United States (n = 84,481). Methods: Gender was self-reported and categorized as male, female, and transgender/nonbinary. Descriptive analyses were conducted, and logistic regression was used to measure associations between loneliness and substance use by gender and substance. Results: Loneliness prevalence was 58% in the sample, and loneliness was most prevalent among transgender/nonbinary students (79%). Loneliness was associated with reduced odds of alcohol use and increased odds of benzodiazepine use in all genders, and increased odds of marijuana, stimulant, and opioid misuse in females and males. Conclusions: Loneliness is prevalent in college students, especially in transgender/nonbinary students, and it is associated with increased odds of substance use. College administrators should consider implementing interventions to reduce loneliness in this population.

The impact of relationship type and closeness on mental health following suicide loss.

BACKGROUND: Most research investigating the effect of suicide on loss survivors has been limited to first-degree family members. Few studies examine the impact of suicide on others outside the immediate family and the influence of relationship type and closeness on mental health. METHODS: This study used data from a sample obtained through random digit dialing (n = 805) to assess exposure to suicide loss, relationship types, perceived closeness, and mental health symptoms (prolonged grief, depression, anxiety, and posttraumatic stress disorder). RESULTS: Familial status, friend status, and higher perceived closeness were associated with prolonged grief, depression, and posttraumatic stress disorder, with the strongest adjusted associations observed for posttraumatic stress disorder and prolonged grief. In general, the magnitude of adjusted standardized associations for closeness and mental health symptoms was stronger than those observed for familial status and mental health symptoms and friend status and mental health symptoms. CONCLUSION: Closeness, familial status, and friend status are associated with mental health symptoms experienced after suicide loss, but the magnitude of associations was strongest for closeness. Future studies should examine perceived closeness in addition to other factors related to relationship type and dynamics to assess the complexities of suicide bereavement reactions.

The role of cardiorespiratory fitness on quality of life in midlife women.

OBJECTIVE: We aimed to characterize the relationship between cardiorespiratory fitness and quality of life in a sample of healthy midlife women aged 40 to 65 years. METHODS: Cardiorespiratory fitness was measured with a VO2max test. Quality of life was assessed with the menopause-specific Utian Quality of Life scale (UQOL). The UQOL measures overall quality of life, which comprises health, emotional, occupational, and sexual domains. Simple and multiple linear regression models were built to analyze relationships between cardiorespiratory fitness and overall quality of life as well as the separate UQOL domains. RESULTS: Forty-nine women with an average age of 52.5 years were included in the analysis. In simple linear models, cardiorespiratory fitness was related to overall (R2 = 0.34, P < 0.001), health (R2 = 0.55, P < 0.001), emotional (R2 = 0.08, P = 0.05), and occupational (R2 = 0.09, P = 0.03) quality of life. In multiple regression models, cardiorespiratory fitness was associated with overall (P < 0.01) and health (P < 0.001) quality of life, after controlling for physical activity, age, body mass index, and time sedentary. CONCLUSIONS: Higher cardiorespiratory fitness is associated with better quality of life during midlife, particularly in the health domain. Increasing cardiorespiratory fitness may be a useful means to promote quality of life in this population.