Association of nickel and chromium levels with p53 and EGFR mutations in Taiwanese lung cancer patients

• Main Authors: Yu-Hu, 邱育瑚
• Other Authors: 李 輝
• Format: Others
• Language: zh-TW
• Published: 2008
• Online Access: http://ndltd.ncl.edu.tw/handle/54343640907343438925

碩士 === 中山醫學大學 === 醫學分子毒理學研究所 === 96 === Lung cancer is the second leading cause of cancer death in Taiwan. Previous studies indicated that smoking is the major cause of lung cancer. More than 85% of lung cancer death were associated with cigarette smoking in western countries. However, about 50% of lung cancer death can be explained by cigarette smoking in Taiwan, especially in Taiwanese women, more than 90% are nonsmokers. Thus, environmental factor(s) other than cigarette smoking may be linked with in Taiwanese lung cancer incidence, especially in nonsmokers. Ni or Cr has been classified by WHO to be a human lung carcinogen based on occupational exposure of both heavy metals increases the lung cancer risk of workers who work in the related industries. Previous studies have indicated that p53 mutation was increased by Ni or Cr treatment mediated through decreased DNA repair capacity. Our previous case-control study indicated that the accumulation of Ni and Cr was associated with lung cancer in Taiwan. Therefore, we would verify whether the accumulation of Ni or Cr could contribute to p53 mutation occurrence in lung cancer. In addition, about 50% of Taiwanese female lung cancer had EGFR mutation, but the etiology of EGFR mutation remains unknown. We thus verify whether the accumulation of Ni or Cr could be associated with EGFR mutation occurrence. In this study, 137 adjacent normal lung tissues were enrolled for the determination of Ni or Cr contents by graphite atomic absorption spectrometry (GAAS). P53 and EGFR mutations in lung tumors were evaluated by direct sequencing, respectively. Our results indicated that lung cancer patients with higher Ni contents had 2.8 and 3.86-fold of the risk of p53 and EGFR mutation occurrence than those with lower Ni contents, respectively (P = 0.019 for p53 mutation; P = 0.068 for EGFR mutation). However, lung cancer patients with higher Cr contents had 2.01-fold of p53 mutation occurrence risk, but it did not reach statistical significance (P = 0.065); however Cr accumulated in lung tissues was not related with EGFR mutation (P = 0.911). Interestingly, the accumulation of Ni and Cr in lung tissues had a synergistic effect on p53 mutation occurrence (OR = 5.92, 95% CI = 1.93-18.15). On the other hands, the additive effect of Ni and Cr on EGFR mutation occurrence was not observed in our studied cases (OR = 2.88, 95% CI = 0.79-10.53). Taken together, the association of p53 and EGFR mutations with Ni and Cr exposure may partially contribute to lung cancer development in Taiwan.