Checkpoint kinase 2 (hCHK2/hCds1) is a tumor suppressor gene involved in 
cell-cycle control. A hCHK2/hCds1 polymorphism in codon 84 (A-->G at nucleotide 
252) was recently identified in Li-Fraumeni syndrome patients. Because cell 
cycle regulates DNA repair that is associated with cancer risk, we hypothesized 
that this new polymorphism exists in the general population and is associated 
with cancer risk. To test this hypothesis, we evaluated the role of this 
polymorphism in a case-control study of 215 non-Hispanic white patients with 
newly diagnosed squamous cell carcinoma of the head and neck (SCCHN) and 229 
frequency-matched cancer-free controls. We found that the hCHK2/hCds1 codon 84 
variant was rare and less frequent in non-Hispanic white cases (0.0186) than in 
controls (0.0437; P = 0.033). Although no variant homozygotes were detected in 
these cases and controls, heterozygosity protected against SCCHN, representing a 
60% reduction of risk (adjusted odds ratio = 0.40; 95% confidence intervals, 
0.17-0.93) compared with wild-type homozygotes. The variant allele was also rare 
in other ethnic groups (0.0487, 0.0095 and 0.0541 in 115 African Americans, 105 
Hispanic Americans and 111 native Chinese, respectively), and only one variant 
homozygous individual (a Chinese subject) was identified. These results suggest 
that this hCHK2/hCds1 codon 84 polymorphism is rare and may have a protective 
role in the aetiology of SCCHN in non-Hispanic whites. Larger studies are 
warranted to confirm this finding and further mechanistic studies are needed to 
understand biological relevance of this polymorphism.