Environmental exposure and p53 mutations in esophageal cancer patients in areas of low and high incidence of esophageal cancer in China.

Esophageal cancer is the 6th most common cancer in the world, and genetic factors (p53 mutations) in addition to the environmental factors (food, nutrition, smoking, drinking, etc.) are involved in its development. In this study, the association between the both factors, environmental risk factors for esophageal cancer and p53 mutations, in tumor tissues was investigated in 77 patients living in a high-incidence area and 50 patients living in a low-incidence area in Hebei Province, China. Among these patients, p53 mutations were observed in about 50%, without regional differences in the respective frequencies. G:C>A:T (G to A or C to T) transition mutations were the major type of mutations observed in patients in the high-incidence area (19 patients, 50%), whereas G:C>A:T transitions and insertions were observed with equal frequency (8 patients, 33.3%) in the low-incidence area. As for the association with environmental factors, p53 mutations occurred with higher frequency in patients with a daily intake of spicy foods and in those who used unboiled well water in the low-incidence area. Logistic regression analysis showed no association between food intakes and p53 mutations in high- and low-incidence areas. Thus, higher frequency of spicy food intake and use of unboiled well water may be risk factors of esophageal cancer via p53 mutations in China.

DHPLC is superior to SSCP in screening p53 mutations in esophageal cancer tissues.

Mutations of the p53 tumor-suppressor gene universally occur on exons 5-8 in human cancer. We analyzed these mutations in esophageal cancer tissue from 207 patients in China using 2 methods, single-strand conformation polymorphism (SSCP), one of the most frequently used methods, and the recently developed denaturing high-performance liquid chromatography (DHPLC), and compared their sensitivity and efficiency. Exons 5-8 of p53 were amplified from esophageal cancer tissue genomes, screened for fragments of mutations and polymorphisms by SSCP and DHPLC in a blind study and confirmed by direct sequencing to detect the mutations and polymorphisms. The numbers detected by DHPLC were greater than those detected by SSCP, though the rate of mutations and polymorphisms was lower in SSCP than in DHPLC, which appeared to detect smaller mutations (substitutions and 1 bp insertions/deletions). Of the mutations with substitutions detected by DHPLC but not by SSCP, 50% substituted adenosine for other nucleotides, suggesting that these mutations are often missed when SSCP is used. According to these data, the sensitivity of SSCP and DHPLC was 81% and 97%, respectively, and the specificity was 97% and 85%, respectively. Our results suggest that DHPLC may be recommended over SSCP when screening gene mutations. Thus, rates of p53 mutations and polymorphisms in esophageal cancer tissue in Chinese patients were 49% and 41% by DHPLC and SSCP, respectively.