Both lung cancer and cardiovascular disease (CVD) are prevalent diseases that contribute to global mortality rates. Although individuals with CVD may face an elevated risk of cancer based on the presence of shared risk factors (such as tobacco smoking and excessive body weight), the roles of somatic mutations and heavy metal distributions remain unknown. The present study aimed to explore the differences in somatic mutations and heavy metal distributions between hypertensive patients and non‑hypertensive patients in a cohort of patients with non‑small cell lung cancer (NSCLC). Tumor tissue samples from 64 patients were analyzed using a next‑generation sequencing panel consisting of 82 tumor‑related genes through hybrid capture. Serum samples were also analyzed to determine the levels of 18 heavy metals using inductively‑coupled plasma mass spectrometry. Among the 16 hypertensive patients, all patients (16/16; 100.00%) harbored 47 somatic mutations in 14 mutant genes, whereas 45 patients without hypertension (45/48; 93.75%) harbored 113 somatic mutations across 26 mutant genes (no mutations were detected in the remaining 3 patients). Among the 32 identified mutant genes in these two groups, FBXW7, CBR3, CDKN2A, HRAS, SMO and UGT1A1 were exclusively observed in patients with hypertension, while 18 mutant genes were only observed in patients without hypertension. No significant mutually exclusive interactions were found in hypertensive patients, but mutually exclusive interactions were observed between EGFR and STK11 (P=0.0240) and between STK11 and KRAS (P=0.0169) in non‑hypertensive patients. ‘Non‑small cell lung cancer’ was the top Kyoto Encyclopedia of Genes and Genomes pathway in hypertensive patients, whereas ‘central carbon metabolism in cancer’ was the top pathway in patients without hypertension. Moreover, the proportions of altered key signaling pathways and biological function categories shared between these two groups were 54.37% (56/103) and 21.62% (8/37), respectively. Furthermore, the levels of chromium (Cr) in the serum of hypertensive patients were notably elevated compared with those in patients without hypertension. In addition, significant negative correlations were observed between Cr and CEA, between CYFRA21‑1 and Zn, and between NSE and As in hypertensive patients but not in non‑hypertensive patients, indicating differing interactive profiles among the traditional serum biomarkers and heavy metals between these two patient groups. In summary, there were differences in genomic alterations, somatic interactions and the serum levels of Cr between patients with NSCLC with hypertension and patients with NSCLC without hypertension. Furthermore, patients with hypertension exhibited significant negative correlations between Cr and CEA, between CYFRA21‑1 and Zn, and between NSE and As, suggesting that heavy metals may contribute to the occurrence of NSCLC with different hypertensive status.

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