Causal relationship between hormone levels and lung cancer: a Mendelian randomization study

Abstract

Background: Lung cancer is a highly prevalent neoplastic disease in various regions of the world, but the mechanism of its occurrence, development, and metastasis is not clear. Different hormone levels have different potential roles in the occurrence, development, and metastasis of lung cancer, but the association between hormone levels and lung cancer is not clear.

Objective: This study aims to explore the causal relationship between hormone levels and lung cancer using Mendelian randomization. Sensitivity and heterogeneity tests were conducted to ensure the reliability of the results, offering insights into the prevention, diagnosis, and treatment of lung cancer.

Methods: We employed a two-sample Mendelian randomization (MR) analysis using large-scale publicly available genome-wide association studies (GWAS) data to assess the causal relationship between hormone levels and lung cancer. We explored the causal relationship between 15 hormones and three subtypes of lung cancer. The inverse variance weighted (IVW) method was used as the primary analysis, while MR-Egger, weighted median, weighted mode, and simple median were applied as supplementary methods. Sensitivity and heterogeneity tests were conducted to ensure the robustness of the findings.

Results: We identified six hormone levels to be significantly associated with lung squamous cell carcinoma (LUSC): total testosterone, oestradiol, thyrotropin-releasing hormone, insulin, parathyroid hormone, and glucocorticoid. Among them, total testosterone, estradiol, and thyrotropin-releasing hormone were negatively correlated with morbidity. Insulin, prolactin levels, and parathyroid hormone were positively correlated with morbidity. Five hormone levels were significantly associated with lung adenocarcinoma (LUAD): luteinizing hormone, thyroid hormones, insulin, prolactin levels, and parathyroid hormone. Luteinizing hormone and thyroid hormones were negatively correlated with morbidity, while insulin, prolactin levels, and parathyroid hormone were positively correlated with morbidity. Similarly, five hormone levels were linked to small cell lung cancer (SCLC): total testosterone, luteinizing hormone, estradiol, PTHrP, and insulin. Total testosterone and luteinizing hormone were negatively correlated with morbidity, while estradiol, Parathyroid Hormone-Related Peptide (PTHrP), and insulin were positively correlated with morbidity. Several hormones were associated with different subtypes of lung cancer. Insulin was significantly associated with all three types of lung cancer. Testosterone showed positive effects in LUSC and SCLC, and estradiol had varying effects, with a negative correlation in SCLC and a positive correlation in LUSC. Testosterone and estradiol were not significantly associated with LUAD. Luteinizing hormone showed positive effects in LUAD and SCLC, and parathyroid hormone showed negative effects in LUSC and LUAD.

Conclusion: This study demonstrates significant causal relationships between specific hormone levels and various types of lung cancer, providing valuable insights for prevention, diagnosis, and treatment strategies of lung cancer.

About this publication.

The Di Bella's Method: Use of Cabergoline and/or Bromocriptine, Somatostatin/Octreotide analogues and/or derivatives associated with pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea (together with others chemical compounds) in Lung Cancer:

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in advanced non-small-cell lung cancer patients with low performance status;

- Somatostatin, retinoids, melatonin, vitamin D, bromocriptine, and cyclophosphamide in chemotherapy-pretreated patients with advanced lung adenocarcinoma and low performance status;

- Observations on the Report of a case of pulmonary adenocarcinoma with lymph node, hepatic and osseus metastasis;

See also: 

- Official Web Site: The Di Bella Method;

- The Di Bella Method (A Fixed Part - Bromocriptine and/or Cabergoline);

- Prolactin inhibitors in oncology - In vitro, review and in vivo publications;

- The Di Bella Method (A Fixed Part - Cyclophosphamide 50mg tablets and/or Hydroxyurea 500mg tablets, one or two per day);

- The Di Bella Method (A Fixed Part - Somatostatin, Octreotide, Sandostatin LAR, analogues and/or derivatives);

- Somatostatin in oncology, the overlooked evidences - In vitro, review and in vivo publications;

- Publication, 2018 Jul: Over-Expression of GH/GHR in Breast Cancer and Oncosuppressor Role of Somatostatin as a Physiological Inhibitor (from Di Bella's Foundation);

- Publication, 2018 Sep: The over-expression of GH/GHR in tumour tissues with respect to healthy ones confirms its oncogenic role and the consequent oncosuppressor role of its physiological inhibitor, somatostatin: a review of the literature (from Di Bella's Foundation);

- Publication, 2019 Aug: The Entrapment of Somatostatin in a Lipid Formulation: Retarded Release and Free Radical Reactivity (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of Somatostatin and Vitamin C on the Fatty Acid Profile of Breast Cancer Cell Membranes (from Di Bella's Foundation);

- Publication, 2019 Sep: Effects of somatostatin, curcumin, and quercetin on the fatty acid profile of breast cancer cell membranes (from Di Bella's Foundation);

- Publication, 2020 Sep: Two neuroendocrine G protein-coupled receptor molecules, somatostatin and melatonin: Physiology of signal transduction and therapeutic perspectives (from Di Bella's Foundation);

The Di Bella's Method: Use Somatostatin/Octreotide analogues and/or derivatives since 1977 with Cabergoline and/or Bromocriptine associated with pseudo-Metronomic Chemotherapy Cyclophosphamide and/or Hydroxyurea - together with others chemical compounds - in several Oncological Pathologies:

- Pleural Mesothelioma: clinical records on 11 patients treated with Di Bella's Method;

- Malignant pleural mesothelioma, stage T3-T4. Consideration of a case study;

- Excellent result in a Mesothelioma case treated exclusively with Di Bella Method for over 4 years and still treatment with positive results;

- A case of advanced Multiple Myeloma treated with Di Bella Method (DBM) into total remission for 13 years;

- Neuroblastoma: Complete objective response to biological treatment;

- Cyclophosphamide plus Somatostatin, Bromocriptin, Retinoids, Melatonin and ACTH in the Treatment of Low-grade Non-Hodgkin’s Lymphomas at Advanced Stage: Results of a Phase II Trial;

- Relapse of High-Grade Non-Hodgkin’s Lymphoma After Autologous Stem Cell Transplantation: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Melatonin, Retinoids, and ACTH;

- Low-grade Non-Hodgkin Lymphoma at Advanced Stage: A Case Successfully Treated With Cyclophosphamide Plus Somatostatin, Bromocriptine, Retinoids, and Melatonin;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 55 cases of Lymphomas;

- Large B-cells Non-Hodgkin's Lymphoma, Stage IV-AE: a Case Report;

- Non-Hodgkin's Lymphoma, Stage III-B-E: a Case Report;

- Oesophageal squamocellular carcinoma: a complete and objective response;

- Pancreatic Adenocarcinoma: clinical records on 17 patients treated with Di Bella's Method;

- The Di Bella Method Increases by the 30% the survival rate for Pancreas tumors and for this reason should be proposed as first line therapy for this type of cancer;

- The Di Bella Method (DBM) in the treatment of prostate cancer: a preliminary retrospective study of 16 patients and a review of the literature;

- A retrospective observational study on cases of Osteosarcomas treated with a multitherapy: The rationale and effectiveness;

- A Retrospective Observational Study on Cases of Sarcoma Treated with the Di Bella Method: Rationale and Effectiveness;

- Congenital fibrosarcoma in complete remission with Somatostatin, Retinoids, Vitamin D3, Vitamin E, Vitamin C, Melatonin, Calcium, Chondroitin sulfate associated with low doses of Cyclophosphamide in a 14-year Follow Up;

- A retrospective observational clinical study of triple negative breast cancer cases treated with Di Bella Method: A preliminary data;

- The Synergism of Somatostatin, Melatonin, Vitamins Prolactin and Estrogen Inhibitors Increased Survival, Objective Response and Performance Status In 297 Cases of Breast Cancer;

- Complete objective response, stable for 5 years, with the Di Bella Method, of multiple-metastatic carcinoma of the breast;

- Evaluation of the safety and efficacy of the first-line treatment with somatostatin combined with melatonin, retinoids, vitamin D3, and low doses of cyclophosphamide in 20 cases of breast cancer: a preliminary report;

- The Di Bella Method (DBM) improved survival, objective response and performance status in a retrospective observational clinical study on 122 cases of breast cancer;

- Complete objective response to biological therapy of plurifocal breast carcinoma;

- A retrospective observational study on cases of anaplastic brain tumors treated with the Di Bella Method: A rationale and effectiveness;

- Recurrent Glioblastoma Multiforme (grade IV – WHO 2007): a case of complete objective response achieved by means of the concomitant administration of Somatostatin and Octreotide – Retinoids – Vitamin E – Vitamin D3 – Vitamin C – Melatonin – D2 R agonists (Di Bella Method – DBM) associated with Temozolomide;

- The Di Bella Method DBM improved survival objective response and performance status in a retrospective observational clinical study on 23 tumours of the head and neck;

- Chronic Lymphocytic Leukemia: Long-Lasting Remission with Combination of Cyclophosphamide, Somatostatin, Bromocriptine, Retinoids, Melatonin, and ACTH.