Hypothyroidism May Be Protective Against Lung Cancer

Hypothyroidism genetically has a protective causal relationship with lung cancer, as well as protective effects on lung adenocarcinoma and squamous cell lung cancer, according to a study in BMC Pulmonary Medicine.

Researchers used Mendelian randomization (MR) analysis to assess the causal relationship between thyroid function and lung cancer.

The hypothyroidism genome-wide association studies (GWAS) included 287,247 Finnish adult individuals from the FinnGen R8 alliance; the hyperthyroidism GWAS included 257,552 Finnish adult participants from FinnGen. Data from the Thyroidomics Consortium (72,167 individuals) were used to evaluate genetically determined thyroid-stimulating hormone (TSH) and free thyroxine (FT4). GWAS data regarding lung cancer, lung adenocarcinoma, and squamous cell lung cancer were from the International Lung Cancer Consortium study of 27,209 European adults.

The 2-sample Mendelian randomization analysis used MR methods that included the inverse variance weighted (IVW) average method, the MR-Egger method, MR-pleiotropy residual sum and outlier, simple mode, weighted mode, and weighted median.

A total of 85 single nucleotide polymorphisms were selected as valid instrumental variables for hypothyroidism. The estimated odds ratio (OR) of hypothyroidism on lung cancer was 0.918 (95% CI, 0.859-0.982; P =.013) in the MR analysis with the IVW method, which indicated that hypothyroidism can lead to an average of an 8.2% decreased risk in lung cancer and suggests that hypothyroidism may have a protective role.

The causal effect of lung cancer on hyperthyroidism from the MR analysis was an estimated OR of 1.068 (95% CI, 0.762-1.497; P =.702) per the IVW method. The causal effect of lung cancer on TSH had an estimated OR of 0.995 (95% CI, 0.945-1.046; P =.832) with the IVW method. Lung cancer’s causal effect on FT4 had an estimated OR of 1.034 (95% CI, 0.972-1.099; P =.290) according to the IVW method.

In the MR analysis with lung cancer as the exposure, no evidence was found for a direct causal effect of lung cancer level (OR, 0.968; 95% CI, 0.909-1.030; P =.303) on hypothyroidism risk per the IVW method.

The causal effect of hypothyroidism on lung adenocarcinoma was an estimated OR of 0.893 (95% CI, 0.813-0.981; P =.019) with IVW, which suggests that hypothyroidism may have a protective role for lung adenocarcinoma. The causal effect of hypothyroidism on squamous cell lung cancer was an estimated OR of 0.888 (95% CI, 0.797-0.990; P =.032) in the IVW method, with the results in the MR analysis suggesting that hypothyroidism had a protective role.

The researchers noted that they were unable to confirm whether TSH and FT4 in patients with hypothyroidism and hyperthyroidism at the genetic level had any effects on lung cancer. Also, the results cannot be generalized to other races, and the GWAS population of lung adenocarcinoma and squamous cell lung cancer was relatively small.

“Our study is the first to demonstrate that hypothyroidism genetically has a protective causal relationship on lung cancer by Mendelian analysis methods,” said the study authors. The findings suggest that more research and discussion are needed regarding whether patients with hypothyroidism at high risk of lung cancer should be actively supplemented with thyroid hormone, the study authors added.

This article originally appeared on Pulmonology Advisor