Absence of association between HPV DNA, TP53 codon 72 polymorphism, and risk of oesophageal cancer in a high-risk area of China
Introduction
Oesophageal cancer is common in several areas of central Asia, including Linxian County in Henan province, China, where age-adjusted mortality rates of up to 161/100 000 have been reported in males [1]. These cancers are mostly, if not exclusively, squamous cell carcinomas (SCC), and show a high frequency of mutation in the TP53 tumour suppressor [2]. Epidemiological studies have suggested a number of risk factors, including deficiencies in vitamins and minerals, consumption of pickled foods and environmental exposure to specific nitrosamines [1], [3]. Viral infections, in particular by human papilloma virus (HPV), have been reported in oesophageal cancers from central China. In the Henan province, Chen et al. [4] have detected HPV DNA in 60.0% of cancer tissues by a polymerase chain reaction analysis using consensus primers for highly conserved E1 region of HPV types 6, 11, 16, and 18. In a recent study in the province of Sichuan, an area of moderate risk for oesophageal cancer, a significant, inverse relationship has been observed between the presence of HPV DNA in tumours and TP53 gene mutation, suggesting that HPV infection might be involved in the etiopathogenesis of oesophageal cancer in China [5]. However, this observation has not been substantiated in areas of China showing the highest risk of oesophageal cancer. Therefore, the role of HPV infection in oesophageal carcinogenesis in these areas is still unresolved [6].
In a study by Storey et al. [7], a common polymorphism at codon 72 of the TP53 gene (CCC, proline/CGC, arginine) has been shown to be associated with an increased risk of cervical cancer. Experimental studies have indicated that the protein containing an arginine at position 72 was more efficiently targeted for degradation by the E6 protein of HPV 16, suggesting that individuals homozygous for the Arg-encoding allele may have an increased susceptibility to HPV-related cervical cancers [7]. However, other population studies have so far failed to confirm this hypothesis [8], [9].
The polymorphism at codon 72 has also been shown to be associated with an increased risk of lung cancer, but the significance of this association remains controversial [10], [11]. In smokers, several studies have suggested an elevated risk associated with the Pro/Pro genotype [11], [12]. In contrast, Arg/Arg homozygotes are frequently found in non-smoking patients with lung cancers [12], [13].
In the present study, we examined the relationship between codon 72 polymorphism in TP53 and the presence of HPV DNA in a series of oesophageal cancer cases and healthy subjects from Henan Province, China.
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Cancer cases and healthy subjects
Thirty-two cases of squamous cell carcinoma of the oesophagus (15 males and 17 females) with a median age of 57 years (range 38–74)) and 57 healthy subjects with normal cytological criteria (19 males and 35 females) with a median age of 40.5 years (range 29–65), used as a comparison group, were included in this study. These samples are part of a large population-based, oesophageal balloon cytology screening programme for oesophageal cancer conducted in He-shun commune in Lin-xian county, Henan
Results
Fig. 1 shows a typical pattern of codon 72 evaluated by restriction analysis. Presence of the Pro allele results in resistance of the PCR amplified DNA fragment to digestion by AccII. Table 1 compares the distribution of TP53 alleles at codon 72 in the cases and healthy subjects studied. The most common genotype was Pro/Pro (homozygote for the proline allele, 42.1% in controls, allele frequency 0.63; 34.3% in cases; allele frequency: 0.55). The proportion of Arg/Arg (homozygote for the arginine
Discussion
The results presented here indicate that the most common allele in this population of central China is the one encoding Proline at position 72, in contrast to the majority of the populations tested to date. We report a frequency of the Pro allele of 0.63 in healthy individuals, and the distribution of the different allelotypes was compatible with the Hardy-Weinberg equilibrium [21].
In various populations of Western Europe (France, Sweden, Norway), North America, Central and South America
Acknowledgements
DPG is supported by a special training award of the International Agency for Research on Cancer.
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