Habitual fish oil supplementation and incident chronic obstructive pulmonary disease: Data from a prospective cohort study.

BACKGROUND: Fish oil is one of the most popular supplements in the UK and other developed countries. However, the relationship between fish oil use and chronic obstructive pulmonary disease (COPD) is unclear. OBJECTIVE: To prospectively examine the association of habitual fish oil supplementation with incident COPD risk and to evaluate potential effect modification by genetic predisposition. METHODS: This study included 484,414 participants (mean and standard deviation [SD] age: 56.5 [8.1] years) from the UK Biobank who completed a touchscreen questionnaire on habitual fish oil supplement use between 2006 and 2010 and were followed up through 2018. Cox regression models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) with adjustment for sociodemographic and lifestyle behaviours, health conditions, and other potential confounding factors. A weighted genetic risk score (GRS) for COPD was derived from 112 validated single nucleotide polymorphisms. RESULTS: During a median follow-up of 9.0 years, 8860 incident COPD events were recorded. A total of 31.4% (152,230) of the study participants reported habitual fish oil supplementation at baseline. Habitual fish oil supplementation was significantly associated with a lower risk of incident COPD (adjusted HR: 0.88; 95% CI: 0.84-0.93). The association with COPD did not differ by GRS strata (P for interaction = 0.880). The results from subgroup and sensitivity analyses supported the robustness of our findings. CONCLUSIONS: Our findings suggest that habitual fish oil supplementation is associated with a lower risk of incident COPD, irrespective of genetic predisposition.

Genetic Risk and Chronic Obstructive Pulmonary Disease Independently Predict the Risk of Incident Severe COVID-19.

Rationale: Both genetic variants and chronic obstructive pulmonary disease (COPD) contribute to the risk of incident severe coronavirus disease (COVID-19). Whether genetic risk of incident severe COVID-19 is the same regardless of preexisting COPD is unknown. Objectives: In this study, we aimed to investigate the potential interaction between genetic risk and COPD in relation to severe COVID-19. Methods: We constructed a polygenic risk score for severe COVID-19 by using 112 single-nucleotide polymorphisms in 430,582 participants from the UK Biobank study. We examined the associations of genetic risk and COPD with severe COVID-19 by using logistic regression models. Results: Of 430,582 participants, 712 developed severe COVID-19 as of February 22, 2021, of whom 19.8% had preexisting COPD. Compared with participants at low genetic risk, those at intermediate genetic risk (odds ratio [OR], 1.34; 95% confidence interval [CI], 1.09-1.66) and high genetic risk (OR, 1.50; 95% CI, 1.18-1.92) had higher risk of severe COVID-19 (P for trend = 0.001), and the association was independent of COPD (P for interaction = 0.76). COPD was associated with a higher risk of incident severe COVID-19 (OR, 1.37; 95% CI, 1.12-1.67; P = 0.002). Participants at high genetic risk and with COPD had a higher risk of severe COVID-19 (OR, 2.05; 95% CI, 1.35-3.04; P < 0.001) than those at low genetic risk and without COPD. Conclusions: The polygenic risk score, which combines multiple risk alleles, can be effectively used in screening for high-risk populations of severe COVID-19. High genetic risk correlates with a higher risk of severe COVID-19, regardless of preexisting COPD.

[Study on the relationship between breast cancer resistance protein expression and 5-fluorouracil resistance].

OBJECTIVE: To screen breast cancer resistance protein BCRP-mediated resistance agents and to investigate the relations between BCRP expression and drug resistance. METHODS: MT assay was performed to screen BCRP-mediated resistant agents with established BCRP expression cell model. While, the high performance liquid chromatography (HPLC) assay was administrated to measure the related dosage of intracellular retention resistant agents. The BCRP expression was investigated by both real-time RT-PCR and immunohistochemistry (IHC) assay in 140 clinical breast cancer tissue specimens. Chemosensitivity to resistant agents for clinical breast cancer tissue specimens was analyzed by MT assay. The Nonparametric variance statistics method was used to analyze the correlations between clinical breast cancer tissue of BCRP expression and drug resistance. RESULTS: MT assay showed that increasing resistance of 5-fluorouracil (5-Fu) climbed with the increases of the BCRP expressions by 10.58 times (P < 0.05, n = 3) in cell model. HPLC assay also proved that a significant negative correlation between the intracellular retention dose of 5-Fu with different expression of BCRP (r = -0.897, P < 0.05, n = 3). Forty-seven tissue specimens of BCRP-positive expression were rapidly determined by using both real-time RT-PCR and IHC in 140 clinical breast cancer tissue specimens. Subsequently, the resistance index (RI) for 47 BCRP-positive clinical breast cancer tissues to 5-Fu was shown from 7 to 12 times compared with normal cancer-side tissues through MT assay. The statistical correlation between BCRP expression and 5-Fu resistance was observed in clinical breast cancer tissue specimens (R2 = 0.8124, P < 0.01). CONCLUSION: This study results showed that there is a significant relationship between BCRP expression and 5-Fu resistance. Moreover, the results suggest that the chemotherapy scheme could be optimized on BCRP-positive expression breast cancer patients.