Association between p21 codon 31 polymorphism and esophageal cancer risk in a Taiwanese population
Introduction
P21 (Waf-1) is a cyclin-dependent kinase inhibitor that is pivotal in arresting cellular growth, in terminal differentiation and in apoptosis [1]. Gene alterations at this site may adversely affect regulation of these processes and increase susceptibility to developing cancer.
Sun and his colleagues [2] reported a polymorphism in the p21 codon 31 that produces a C to A transversion and causes a substitution from serine (ser) to arginine (arg). Subsequently, a series of epidemiologic studies have examined the effect of this polymorphism on lung cancer, cervical cancer, breast cancer and nasopharyngeal cancer with conflicting results [3], [4], [5], [6], [7], [8], [9]. The ser allele has been suggested to be a risk factor for cancers in breast and cervix [4], [5], whereas the arg allele has been associated with the development of lung cancer [3]. Since no one to our knowledge has investigated the polymorphic effect of the p21 codon 31 on esophageal cancer risk, we decided to pursue such an inquiry.
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Cases and controls
Over a two-year period, we recruited 128 patients with pathologically proved esophageal squamous cell carcinoma. All were undergoing treatment at either Kaohsiung Medical University Hospital or Kaohsiung Veterans General Hospital, both located in southern Taiwan. Concurrently, the Department of Preventive Medicine at each hospital chose to use 1–2 control subjects (n=178) who had not malignancy but would be willing to provide blood specimens to match in age (±3 years) and time of presentation
Results
Mean age (range) was 58.8 (26–82) years for the 128 cases and 58.8 (28–84) years for the 178 controls. Prevalence (number) in the controls was 28.6% (51/178) for arg/arg, 47.2% (84/178) for arg/ser and 24.2% (43/178) for ser/ser. Gene frequency of the ser allele was 47.8%. Distribution of different genotypes among 178 controls closely conformed to expected Hardy–Weinberg frequencies (χ2=0.26; d.f.=2; P=0.88).
Table 1 shows that educational level (p<0.01) and habitual use of cigarettes (p<0.01),
Discussion
Overall, subjects with the arg/ser or ser/ser genotype were 2.17 times more at risk ) for developing esophageal cancer than were those with the arg/arg genotype. A slightly stronger association of esophageal cancer with arg/ser or ser/ser genotypes was found in males.
P21 is a cyclin-dependent kinase inhibitor that plays a pivotal role in arresting cellular growth. In response to DNA damage, p21 is induced by the p53 gene, thereby directly mediating p53-induced G1 arrest [1], [6]
Acknowledgements
We thank Mr James Steed for helping us edit this manuscript. This research was supported by grants from the Taiwan National Science Council (NSC 90-2320-B-037-040 and NSC 90-2320-B-037-052), the Taiwan National Health Research Institute (NHRI-CN-IN-9007P) and the Faculty Research Innovation Fund of Kaohsiung Medical University (Drs T.F. Chen and O.L. Chen).
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