Abstract
Individuals living in the industrialized countries are exposed extensively to air pollutants and chemicals that cause DNA mutations, cancer and birth defect. Recent studies have suggeted that inherited differences in metabolic capacity may play a primary role in susceptibility to environmentally induced cancers. In this respect, polymorphic alleles of Glutathione S-Transferase (GSTM1) which is important in the detoxication of several carcinogens were analyzed the 104 controls and 172 patients with lung cancer in Sheng-Yen district of China. The frequencies of GSTM1 gene deletion was significantly higher in the patients with lung cancer than in control (p<0.01). GSTM1 gene deletion was found to be higher risk factor in small cell carcinoma than in squamous cell carcinoma and adenocarcinoma.
In our recent studies, allelic polymorphism of aldehyde dehydrogenase 2 (ALDH2) have revealed that the ALDH2*2 frequency was less common in alcoholics compared with healthy controls. This observation indicates that individuals possessing ALDH2*2 may refrain from excessive drinking due to averse reaction caused by a raise of blood acetaldehyde level. In this sense, ALDH2*2 plays a protective role against alcoholism. This mutant was found only in Mongoloid population groups. In our country, the higher frequency of the mutant was found in Kinki- and Chubu-district (28.4% and 27.2%). On the contrary, Kyusyu- and Tohoku-district were found to be lower (20.9% and 18.8%). These data suggested a possible existence of gene-cline for the ALDH2*2 allele.
Recently, Cloninger et al. (1993) proposed that the heritable human personality traits consist of four distinct domains of temperaments designated as Novelty Seeking (NS). Harm Avoidance (HA), Reward Dependence (RD) and Persistence (P) by the experimental data to be based on neurochemical reaction to various substrates. Each subcomponent is mediated by genetic variability of central nerve system for dopamine, serotonin and noradrenalin. In our study, genetic variation in promoter and the coding regions of the CCK gene were analyzed among healthy volunteers to find genetic polymorphism by using PCR, SSCP and Sequencing techniques. We found a frequent mutation at nucleotide position- 45 C to T involved in core sequence of Sp1 binding cis-element of the promoter region. TPQ data were analyzed separately in CC, CT and TT genotypes. Analysis of variance revealed that the group of subjects (CT and TT) with the -45 T exhibit significantly elevated HA scores in comparison to subject (CC) lacking the -45 T. The blood concentration of CCK peptides was significantly lower in the subjects with CT and TT compared with CC. Our data indicated that the nucleotide replacement at -45 C to T in promoter may affect the production of CCK peptide, and this might influence to HA scores.
