Common genetic variants of TP53 and BRCA2 in esophageal cancer patients and healthy individuals from low and high risk areas of northern China

PR Taylor, MD, ScD

National Cancer Institute, Bethesda, Maryland United States

AIM: TP53 and BRCA2 are frequently mutated in cancer and polymorphisms of these genes may modify cancer risk. In this study we assessed and compared the frequency of selected known polymorphisms in TP53 and BRCA2 in healthy Chinese subjects at varying risk of esophageal squamous cell cancer (ESCC) and in ESCC cases. METHODS: We used SSCP and DNA sequencing to test for Arg72Pro (TP53) and 203G>A, Asn372His, and Lys1132Lys (BRCA2) polymorphisms in healthy blood bank volunteers from low (n=101) and high (n=131) risk areas, and from ESCC patients (n=120). RESULTS: The low risk area population was not in Hardy-Weinberg equilibrium (HWE) for either Arg72Pro or Asn372His, while ESCC cases were not in HWE for 203G>A. Suggestive overall differences in the distributions of genotypes by risk groups were seen for all genotypes except Lys1132Lys (chi-square, 4 df=8.564, p=0.079 for Arg72Pro; chi-square, 4 df=0.301, p=0.036 for 203G>A; chi-square, 4 df=14.549, p=0.006 for Asn372His). The differences in Arg72Pro and Asn372His were due to especially low prevalences in our low risk control group (0.16 vs 0.18 in high risk group vs 0.27 in ESCC group for Pro/Pro Arg72Pro genotype; 0.00 vs 0.08 in high risk group vs 0.09 in ESCC group for His/His Asn372His genotype), likely a reflection of lack of HWE. In contrast, the difference in 203G>A was due to low prevalence of G/G in ESCC patients (0.22 vs 0.36 in high risk group vs 0.40 in low risk group), suggesting an association with disease. CONCLUSIONS: These data suggest that the 203G>A polymorphism in BRCA2 may be associated with risk of ESCC.

KEY WORDS: esophageal cancer, polymorphism, cancer risk, China.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Environment and Occupation.

This presentation received an honorable mention in our poster contest and was recognized with the Symposium Presidents' Award for Scientific Excellence.