Exploring gene mutation dynamics in lung carcinogenesis through multistage models in Japanese and Chinese populations

Abstract

Lung cancer plays a significant role in the rising rates of cancer around the world, particularly in Japan and China. In Japan, it is the second most common type of cancer and the fourth leading cause of cancer deaths for both men and women. Meanwhile, in China, lung cancer is the top cause of cancer-related deaths, as highlighted by the National Cancer Center’s 2022 report. This study seeks to find out how many genetic mutations are necessary for lung cancer to develop in men and women from these countries. By examining age-specific lung cancer data, we construct multistage models to estimate mutation rates and how cancer cells grow. We also look into the effects of genomic instability and mutator phenotypes on cancer progression. To test our hypotheses, we apply various statistical methods like P-values, Chi-square tests and the Akaike Information Criterion (AIC), where lower P-values provide stronger evidence against the null hypothesis. Our findings indicate that reducing the rate at which cells proliferate could be more effective in lowering lung cancer risk than merely focusing on mutation rates. The number of driver mutations needed for lung cancer varies: in Japan, it ranges from two to nine mutations, around five in China, and between two and six in the United States. These variations are influenced by a mix of lifestyle choices, genetic backgrounds and environmental factors, with gender differences also playing a role in how lung cancer develops.