Abstract
Lung cancer is the leading cause of cancer-related death worldwide. Exposure to environmental and occupational carcinogens is an important cause of lung cancer. One of these substances is chromium, which is found ubiquitously across the planet. The International Agency for Research on Cancer has classified chromium(VI) as a human carcinogen. The aim of this study was to assess whether serum chromium levels, as well as DNA variants in selected genes involved in carcinogenesis, xenobiotic-metabolism, and oxidative stress could be helpful in the detection of lung cancer. We conducted a study using 218 lung cancer patients and 218 matched healthy controls. We measured serum chromium levels and genotyped ten genetic variants in ERCC2, XRCC1, MT1B, GSTP1, ABCB1, NQ01, CRTC3, GPX1, SOD2 and CAT. The odds ratios of being diagnosed with lung cancer were calculated using conditional logistic regression with respect to serum chromium level and genotypes. The odds ratio for the occurrence of lung cancer increased with increasing serum chromium levels. The difference between the quartiles with the lowest vs. highest chromium level was more than fourfold in the entire group (OR 4.52, CI 2.17–9.42, p < 0.01). This correlation was significantly increased by more than twice when specific genotypes were taken into consideration (ERCC–rs12181 TT, OR 12.34, CI 1.17–130.01, p = 0.04; CRTC3–rs12915189 non GG, OR 9.73, CI 1.58–60.10, p = 0.01; GSTP1–rs1695 non AA, OR 9.47, CI 2.06–43.49, p = < 0.01; CAT–rs1001179 non CC, OR 9.18, CI 1.64–51.24, p = 0.01). Total serum chromium levels > 0.1 μg/L were correlated with 73% (52/71) of lung cancers diagnosed with stage I disease. Our findings support the role of chromium and the influence of key proteins on lung cancer burden in the general population.
Highlights
Lung cancer remains the most common cause of death among all cancers, contributing to over a million people annually succumbing to this disease worldwide
It is important to improve the possibility of early detection through effective screening tests, which would result in a reduction in lung cancer mortality
Our aim was to assess whether serum chromium levels, as well as DNA variants in selected genes involved in carcinogenesis, xenobiotic-metabolism, and oxidative stress could be helpful in the detection of lung cancer
Summary
Lung cancer remains the most common cause of death among all cancers, contributing to over a million people annually succumbing to this disease worldwide. It is important to improve the possibility of early detection through effective screening tests, which would result in a reduction in lung cancer mortality. Diagnostic imaging of the thorax is used for early detection of lung cancer using radiological methods, liquid biopsy and, more recently, epigenetic markers. Research on methods of early lung cancer detection by computed tomography (CT) has provided ambiguous results. In an American study on nearly 55,000 people at high risk of lung cancer it was shown that CT screening resulted in a reduction in mortality by 20% through the use of low-dose CT screening compared with standard chest radiography [2]. The results of studies on Europeans with fewer numbers of people at risk of lung cancer gave inconsistent results [3, 4]. Diagnostic imaging can often lead to the misreading of results and result in false positive of lung nodules for which malignancy could not be defined prior to surgery and pathology [4]
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