Cancers and COVID-19 Risk: A Mendelian Randomization Study

Li, Zengbin; Wei, Yudong; Zhu, Guixian; Wang, Mengjie; Zhang, Lei

doi:10.3390/cancers14092086

Cited by 20 publications

(18 citation statements)

References 61 publications

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“…Based on our current findings, a worse symptom of COVID-19 does not seem to represent a risk factor for EC development, while future investigations are warranted to further establish or rule out our findings. By applying a reverse directional MR design, we further confirmed that genetically predicted female-specific cancers appear not to affect either the susceptibility or the severity of COVID-19, concordant with a previous MR study 43 .…”

Section: Discussionsupporting

confidence: 87%

Are female-specific cancers long-term sequelae of COVID-19? Evidence from a large-scale genome-wide cross-trait analysis

Zhao

Xiao

et al. 2022

Preprint

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Background: Little is known regarding the long-term adverse effects of COVID-19 on female-specific cancers due to the restricted length of observational time, nor the shared genetic influences underlying these conditions. Methods: Leveraging summary statistics from the hitherto largest genome-wide association studies conducted in each trait, we performed a comprehensive genome-wide cross-trait analysis to investigate the shared genetic architecture and the putative genetic associations between COVID-19 with three main female-specific cancers: breast cancer (BC), epithelial ovarian cancer (EOC), and endometrial cancer (EC). Three phenotypes were selected to represent COVID-19 susceptibility (SARS-CoV-2 infection) and severity (COVID-19 hospitalization, COVID-19 critical illness). Results: For COVID-19 susceptibility, we found no evidence of a genetic correlation with any of the female-specific cancers. For COVID-19 severity, we identified a significant genome-wide genetic correlation with EC for both hospitalization (r_g=0.19, P=0.01) and critical illness (r_g=0.29, P=3.00*10-4). Mendelian randomization demonstrated no valid association of COVID-19 with any cancer of interest, except for suggestive associations of genetically predicted hospitalization (ORIVW=1.09, 95%CI=1.01-1.18, P=0.04) and critical illness (ORIVW=1.06, 95%CI=1.00-1.11, P=0.04) with EC risk, none withstanding multiple correction. No reverse association was found. Cross-trait meta-analysis identified multiple pleiotropic SNPs between COVID-19 and female-specific cancers, including 20 for BC, 15 for EOC, and 5 for EC. Transcriptome-wide association studies revealed shared genes, mostly enriched in the hematologic, cardiovascular, and nervous systems. Conclusions: Our genetic analysis highlights an intrinsic link underlying female-specific cancers and COVID-19 - while COVID-19 is not likely to elevate the immediate risk of the examined female-specific cancers, it appears to share mechanistic pathways with these conditions. These findings may provide implications for future therapeutic strategies and public health actions.

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Section: Discussionsupporting

confidence: 87%

Are female-specific cancers long-term sequelae of COVID-19? Evidence from a large-scale genome-wide cross-trait analysis

Zhao

Xiao

et al. 2022

Preprint

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“…KS is the most prevalent HIV-associated malignancy and is among the top 10 cancers in most sub-Saharan Africa countries (GLOBOCAN, 2022). Despite previous studies observing no increased risk of COVID19 among patients presenting with some of the most common cancers [ 11 ], individuals with HIV-associated KS may be an exception due to the role of HIV in KS pathogenesis and in compromising T cell immunity in this population.…”

Section: Introductionmentioning

confidence: 83%

SARS-CoV-2-Specific T Cell Immunity in HIV-Associated Kaposi Sarcoma Patients in Zambia

Ngalamika

Mukasine

Kamanzi

et al. 2022

Journal of Immunology Research

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Severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) virus is the cause of coronavirus disease 2019 (COVID-19). It has caused millions of infections and deaths globally over a 2-year period. Some populations including those living with HIV and/or cancer are reported to be at a higher risk of infection and severe disease. HIV infection leads to a depletion of CD4+ T cells which impairs cell-mediated immunity and increases the risk of malignancies such as Kaposi sarcoma (KS) and viral infections such as SARS-CoV-2. However, several other factors including level of immunosuppression and chemotherapy may also affect the immune response against SARS-CoV-2. In this study, we investigated factors affecting SARS-CoV-2-specific T cell immunity towards the spike, nucleoprotein, membrane protein, and other open reading frame proteins in individuals with HIV-associated KS. The KS patients were SARS-CoV-2 seropositive with detectable T cell responses, but had no history of symptomatic SARS-CoV-2 infection. We observed that the T cell responses increase from baseline levels during follow-up, with responses towards the NMO peptide pool being statistically significant. Low CD4 counts below 200 cells/μl were associated with lower SARS-CoV-2-specific T cell responses. Cancer chemotherapy and KS T staging did not have a significant effect on the T cell responses.

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“…e controversy surrounding this issue may be due to limitations from the involvement of participants with known high-risk health behaviours, such as smoking or alcohol addiction, and family histories of cancer [9][10][11].…”

Section: Introductionmentioning

confidence: 99%

Association between Blood Donation and Malignant and Benign Tumour Risk: A Population-Based Study of 3.4 Million Participants in China

Sun

et al. 2022

Journal of Oncology

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This study aims to identify the relationship between blood donation and malignant and benign tumour hospitalization risk. The cohort study was constructed in Shaanxi, China, to include blood donors and match nonblood donors one-to-one by gender, age, and county of residence. The study compared the hospitalization records of two groups from 2012 to 2018. A log-binomial regression model was used to estimate the relative risk (RR) of tumour risk between donors and nonblood donors among different age groups. A total of 1,625,599 donors were recruited (including 968,823 males) and compared with the matched nonblood donor group. Significantly lower risk of malignancy in males was found among donors (adjusted RR: 0.82, 95% CI: 0.75–0.92). Lower risks for specific types of tumours among donors were observed, including liver (0.42, [0.28–0.67]), lung (0.74, [0.59–0.87]), lymphoma (0.75, [0.62–0.85]), and oesophagus (0.55, [0.41–0.72]). However, the risk of brain cancer was higher among male donors (RR 1.19 [1.06–1.29]). Among female donors, lower risk of liver (0.57, [0.42–0.79]) and oesophagus malignancy (0.73, [0.62–0.88]) was observed. For benign tumours, male donors have a lower risk of benign skin tumour (0.79, [0.62–0.94]) and hemangioma and lymphangioma (0.75, [0.51–0.89]), while female donors have a lower risk in hemangioma and lymphangioma (0.65, [0.44–0.83]). We also found that the risk decreased with age among donors in the prevalence of tumours compared to that in nonblood donors ( p < 0.05 ). Blood donation appears to be significantly associated with various tumour risks among both males and females. Overall, the risk of tumours decreased more substantially with age in blood donors compared with nonblood donors. Further research is warranted to investigate the impact of ‘health donor effects’ on these findings.

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Cancers and COVID-19 Risk: A Mendelian Randomization Study

Cited by 20 publications

References 61 publications

Are female-specific cancers long-term sequelae of COVID-19? Evidence from a large-scale genome-wide cross-trait analysis

Are female-specific cancers long-term sequelae of COVID-19? Evidence from a large-scale genome-wide cross-trait analysis

SARS-CoV-2-Specific T Cell Immunity in HIV-Associated Kaposi Sarcoma Patients in Zambia

Association between Blood Donation and Malignant and Benign Tumour Risk: A Population-Based Study of 3.4 Million Participants in China

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