Differences in p53 gene polymorphisms between Korean schizophrenia and lung cancer patients
Introduction
The relationship between schizophrenia and cancer has posed an epidemiological puzzle for decades (Jablensky and Lawrence, 2001). Lower incidence of malignancies, especially lung cancer, in patients of schizophrenia compared to the general population has been reported in several studies Gulbinat et al., 1992, Mortensen, 1994. Recently, reduced risk of cancer in patients of schizophrenia has been reported in an additional study (Cohen et al., 2002). Theories proposed to date attempting to explain the reduced risk of cancer in schizophrenia patients focused on environmental, genetic, pharmacological, and psychosomatic factors (Cohen et al., 2002). Particular attention has been paid to the question whether genetic predisposition towards schizophrenia confers genetically reduced susceptibility to cancer. However, little is known whether patients with schizophrenia possess genetic factors that also confer tumor resistance, especially to lung cancer.
Catts and Catts (2000) suggested that the reduced incidence of cancer observed in schizophrenia patients might be linked to differences in apoptosis, and proposed p53, a tumor suppressor gene, which is considered as a candidate gene for the susceptibility. The p53 gene is one of the most frequently mutated genes in all types of cancers including lung cancer (Sidransky and Hollstein, 1996). Two polymorphic sites in the sequence of the p53 gene, a BstUI restriction site at codon 72 in exon 4 and an MspI site in intron 6, have been proposed as responsible for the susceptibility to lung cancer Biros et al., 2001, Kawajiri et al., 1993. In this study, we investigated polymorphisms in the two restriction sites of the p53 gene in Korean schizophrenia and lung cancer patients.
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Subjects and method
The schizophrenia patient group consisted of 179 Korean schizophrenia patients diagnosed according to DSM-IV; the mean age was 42.2±11.1 years (mean±S.D.). The lung cancer patient group consisted of 104 Korean patients diagnosed with lung cancer; the mean age was 63.5±10.6 years (mean±S.D.). Written informed consent was obtained from all subjects.
Genomic DNA was extracted from the peripheral blood according to routine procedures. Genotyping for the two polymorphisms, the BstUI in exon 4 (codon
Results and discussion
The genotype and allele frequencies of BstUI and MspI RFLPs in the schizophrenia and lung cancer groups are shown in Table 1. Both groups did not show significant deviations from Hardy–Weinberg equilibrium.
For the BstUI polymorphism, there was no significant difference in the genotype and allele frequencies between the schizophrenia patient and the lung cancer patient groups (genotype frequency: p=0.19, allele frequency: p=0.10; Fisher's exact test). However, both the genotype and allele
Acknowledgments
This study was supported by a Biomedical Brain Research Center grant from the Ministry of Health and Welfare of the Republic of Korea (01-PJ8-PG6-01NE01-0003).
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These authors contributed equally to this work.