Relationships of TP53 codon 72 and HRAS1 polymorphisms with lung cancer risk in an ethnically diverse population

Tobacco smoking is a strong cause of lung cancer, However, because only a s mall proportion of smokers develop the disease, other factors, including ge netic susceptibility, may be important in determining lung cancer risk. Pol ymorphisms in the TP53 tumor suppressor gene and HRAS1 proto-oncogene have been associated in some studies with this cancer; we sought to replicate th ese associations in an ethnically diverse population in Hawaii, We conducte d a population-based case-control study among 334 incident lung cancer case s and 446 controls of Caucasian, Japanese, or Native Hawaiian origin, In-pe rson interviews collected detailed information on lifestyle risk factors. D NA was extracted from peripheral blood leukocytes, and genotyping was perfo rmed using a PCR-based assay for the TP53 codon 72 polymorphism and Souther n blot analysis and PCR for allelic polymorphisms in the HRAS1 minisatellit e, Logistic regression analyses were used to compute odds ratios (ORs) and 95% confidence intervals (CIs) adjusting for smoking and other risk factors , The presence of two rare HRAS1 alleles was associated with a 2.2-fold (95 % CI, 1.0-5.0) increased lung cancer risk for all ethnic groups combined. T he association was present in Native Hawaiians (OR, 5.2; 95% CI, 1.1-24.4) and was suggested for Japanese (OR, 2.8; 95% CI, 0.6-12.5); no association was observed in Caucasians (OR, 0.8; 95% CI, 0.2-3.6), This association was also observed for each lung cancer cell type. The presence of only one rar e allele did not increase risk for any ethnic group or cell type. No signif icant association was found between the TP53 codon 72 polymorphism and lung cancer [OR, 1.4 (95% CI, 0.8-2.4) for the Pro/Pro genotype compared with t he Arg/ Arg genotype], This study suggests that the presence of two rare HR AS1 alleles confers an increased lung cancer risk in Native Hawaiians and J apanese but possibly not in Caucasians, The amino acid replacement of argin ine by proline at codon 72 of TP53 appears not to be important in determini ng lung cancer risk in this population.