Association Of P53 Pro72Arg Polymorphism With Susceptibility To Esophageal & Cardiac Cancer In South And North Of China

Background and ObjectiveEsophageal cancer (EC) and Cardiac cancer (CC) are common cancers globally with great diversity in their incidences. Chaoshan littoral and Taihang mountains both belong to the six EC&CC high risk areas in China. Although the two areas are completely different in environment and people's lifestyle, they are almost the same in incidences, family aggregation and pathology types of EC&CC. It is a clue show the hereditary susceptibility may play an important role in the carcinogenesis of EC&CC. Tumor suppressor gene p53 has a tight relationship with almost all kinds of human malignancies. p53 gene codon72 polymorphism (p53 Pro72Arg,rs1042522) results from a single base change (from CGC to CCC). The p53 Pro72Arg polymorphism genotype distribution has geographical and ethnical diverse. Previous studies have shown its association with many kinds of human cancer, however, its significance as a genetic susceptibility factor of cancer is still a matter of controversy. We detecte p53 Pro72Arg polymorphism genotype on cases and controls from Chaoshan littoral and Taihang mountains, observe the distribution of p53 Pro72Arg polymorphism genotype in the two high risk populations and compare our results with other population from other races or areas in the world and other areas in China using references and public data. And we also compare the results of cases with controls in order to investigate the relationship between Pro72Arg polymorphism and EC& CC susceptibility in the two high incidence areas.Materials and MethodsSample Resources: Peripheral blood samples from Chaoshan and Taihang had been collected by our group since 2002. Cases were the EC or CC patients from hospitals of these two areas including 461 samples from Chaoshan and 421 samples from Taihang. Controls were the healthy subjects who took part in the survey of EC high risk group in these two areas, including 499 samples from Chaoshan and 500 samples from Taihang. All the samples were Chinese Han nationality with their native place in these two high risk areas.Experiment Methods: Genomic DNA was extracted from peripheral blood leukocytes using the UltraPureTM DNA extraction kit (Beijing SBS Genetech C0.,Ltd.); PCR was conducted to amplificate DNA squencece including p53 codon 72. Primers were designed by Primer Primier 5.0 software. The genotypes were evaluated separately by DNA microarray using a method called gel-based microarray for SNP genotyping and a verification of sample drawing DNA sequencing was followed.Statistic Methods: Other data from references and public data were collected for comparing with our results. Area, sex, age, smoking habit and digestive tract tumor family history are used as layers in case-control study. Chi square test was used for the comparison of the frequencies of genotypes and alleles. Unconditional logistic regression was used to evaluate the risk of EC or CC (adjusted by sex and age).Results1. The p53 Pro72Arg allele frequence distribution in our control populations was identical(χ2 =0.67, P=0.41). When compared with other normal populations in different areas of China published in other studies including Zhuang nationality, the p53 Pro72Arg allele frequence distributions were identical too, while with other races in the world, the results showed some significant differences.2. The genotypes distribution of p53 Pro72Arg polymorphism was significantly different between EC patients and healthy subjects (P=0.03). When Compared with p53 Pro72Arg Arg/Arg genotype, carrying Pro/Arg and (Pro/Pro+Pro/Arg) genotype increased the risk of EC, the age, sex adjusted OR=1.37(95%CI 1.04-1.80)and 1.38(95%CI 1.06-1.79). Furthermore, the risk associated with the Pro/Pro variant genotype was more pronounced in younger patients (≤50 years) (OR, 1.89; 95% CI, 1.03-3.45).Conclusions1. The two high incidence areas of esophageal cancer and cardiac cancer—Chaoshan Littoral in south China and the Taihang Mountains in north China shared same p53 Pro72Arg genetic background. Compared with other reports, it's identical in Han nationality from different parts of China and Zhuang nationality, too.2. Pro allele might be correlated with EC carcinogenesis in our objective population. The Pro/Pro genotype was significantly associated with the increased risk of EC in younger population.3. p53 Pro72Arg polymorphism Pro/Pro homozygote could be a biomarker associated with EC susceptibility.