DNA repair gene hOGG1 codon 326 and XRCC1 codon 399 polymorphisms and bladder cancer risk in a Japanese population.

BACKGROUND: Bladder cancer is the most common urologic malignancy in the USA. Tobacco smoking generates oxidative DNA damage and induces bladder cancer. Base excision repair (BER) is a very important mechanism for repairing oxidative DNA damage. There are many enzymes involved in BER. Human oxoguanine glycosylase 1 (hOGG1) and X-ray repair cross-complementing 1 (XRCC1) are enzyme genes of BER. Actually, the hOGG1 codon 326 polymorphism was associated with the risk of lung oesophagus and stomach cancer. On the other hand, among several XRCC1 gene polymorphisms, codon 399 polymorphism was reported to reduce the risk of bladder cancer and raise the risk of lung cancer. METHODS: We examined the association between the genetic polymorphisms of hOGG1 codon 326 and XRCC1 codon 399 and bladder cancer risk. In this study, we recruited 251 bladder cancer cases and 251 healthy controls to evaluate the effect of hOGG1 codon 326 and XRCC1 codon 399 polymorphisms on bladder cancer. We detected genotypes by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. RESULTS: The frequencies of the hOGG1 codon 326 genotypes Cys/Cys was significantly higher in the cases than in the controls. Adjusted odds ratio (OR) was 1.85 (95% CI: 1.12-3.03; p = 0.02) compared with Ser/Ser, and was 2.05 (95% CI: 1.36-3.08; p = 0.01) compared with Ser/Ser + Ser/Cys. In addition, when evaluated with smoking status, the adjusted OR (Cys/Cys versus Ser/Ser + Ser/Cys) ran up to 2.78 (95% CI: 1.39-5.60; p < 0.01) among non-smokers. For the XRCC1 polymorphism, the Gln/Gln of XRCC1 codon 399 genotype was statistically higher in the controls than in the cases though compared with Alg/Alg + Alg/Gln. The adjusted OR was 0.45 (95% CI: 0.21-0.99; p = 0.05), and was lifted up to 0.37 (95% CI: 0.14-0.98; p = 0.05) among smokers. CONCLUSION: It is indicated that the hOGG1 codon 326 and XRCC1 codon 399 polymorphisms are risk factors of bladder cancer.

Application of aldehyde dehydrogenase 2 (ALDH2) genetic diagnosis in support of decreasing alcohol intake.

Encouraging behavioral changes to decrease alcohol intake is not easy from the standpoint of health support. This study was conducted to examine whether the genetic diagnosis of ALDH2 polymorphism is useful in supporting those who want to decrease their alcohol intake. The participants in this study were 329 male employees who wanted to know the result of their ALDH2 genotype. We divided the 329 participants randomly into two groups. One was the "notified group" (n=157), and the other was the "non-notified group" (n=172). The subjects belonging to the "notified group" were informed of the results of the ALDH2 genotype diagnosis in April, 2003. Drinking habits and laboratory data were obtained before and after notification of the ALDH2 genotype. Among those with genotype ALDH2*1/*1, there was no significant change in drinking frequencies, nor was there any significant decline in liver function laboratory data in either of the groups before and after notification of the genotype. However, weekly alcohol intake tended to increase compared to that before notification. On the other hand, with regard to those with genotype ALDH2*1/*2, no significant changes in drinking frequencies or liver function laboratory data were evident in either group before and after notification of the genotype. However, the weekly alcohol intake tended to increase in the non-notified group, whereas it tended to decrease in the notified group. Although the result was not significant, it is suggested that, with further study and an increased sample size, the genetic diagnosis may be found to be useful.

[Relationship of changes in radius bone mineral density during seven years in working women around thirty years old with lifestyle, body measurement data and laboratory data].

OBJECTIVES: A longitudinal study was conducted to investigate the relationships of the change in radius bone mineral density for seven years with lifestyle, body measurement data and laboratory data. METHODS: The subjects of this study were 191 female employees working in an LSI manufacturing factory in Japan. Bone mineral density was measured on the radius of their nondominant side using DXA (dual energy X-ray absorptiometry) in 1995 and 2002. Other medical examinations were performed at the same time. Multiple regression analysis was also performed with the change in radius bone mineral density as the dependent variable. RESULTS: As a result of the multiple regression analysis, a significant positive correlation was observed between the change in body mass index (BMI) and the change in bone mineral density among the subjects aged 30 years and over and those under 30 years. A significant positive correlation was observed between daily milk intake and the change in bone mineral density among those aged under 30 years. A significant negative correlation was observed between daily alcohol intake and the change in bone mineral density among those aged under 30 years, and also between parity and the change in bone mineral density among those aged 30 years and over. CONCLUSIONS: BMI, parity, daily milk intake and daily alcohol intake are considered as significant factors that contribute to a change in bone mineral density. It is necessary that the recommended timing for medical examination be set according to age, and that a well-balanced guidance be provided from young adulthood.

[Consciousness survey regarding genetic diagnosis of glutathione S-transferase M1 (GSTM1) and aldehyde dehydrogenase 2 (ALDH2) polymorphism].

A Consciousness survey regarding genetic diagnosis of GSTM1 and ALDH2 was performed to evaluate the potential use of such a diagnosis in supporting those wanting to stop smoking and decrease alcohol intake. A questionnaire was given to 1,654 employees (male: 1,225, female: 429) who worked at an LSI manufacturing factory, and 1,434/1,654 (86.7%) responded to the survey. The number of respondents who replied that they "wanted to know the results of the genetic diagnosis of GSTM1 and ALDH2" were 731/1,401 (52.2%) and 812/1,434 (56.6%), respectively while the numbers of respondents who replied that they "did not want to know the results" were 138/1,401 (9.9%) and 103/1,434 (7.2%), respectively. The main reasons given for wanting to know the results of the genetic diagnosis of their enzymes reflected the respondents' awareness of their genetic susceptibility. These reasons included a desire to know the effects of tobacco smoke, to prevent diseases in the future, to know the effects of passive smoking or to know their tolerance for alcohol. On the other hand, the main reason for not wanting to know the genetic results that the respondents had no intention of stopping smoking and heavy drinking, or that they would be unable to stop even if they knew the results of the genetic diagnosis. Multiple regression analysis showed that the number of respondents who "wanted to know the results of the genetic diagnosis" was significantly higher among those respondents who are current smokers (male: OR = 1.66 95%CI 1.29-2.14, female: OR = 2.33 95%CI 1.37-3.98), those who understood the relationship between smoking and lung cancer (male: OR = 1.81 95%CI 1.25-2.63, female: OR = 2.77 95%CI 1.42-5.40) and those who with a high CAGE test score (male: OR = 1.96 95%CI 1.42-2.68, female: OR = 2.52 95%CI 1.07-5.94). The results of this survey suggest that genetic diagnosis of GSTM1 and ALDH2 polymorphism may be useful in supporting those who want to stop smoking and decrease their alcohol intake.

Human Glutathione S-transferase A1 polymorphism and susceptibility to oral squamous cell carcinoma in Japanese.

OBJECTIVES: Glutathione S-transferase (GST) A1 catalyses the activated heterocyclic aromatic a mine carcinogenN-acetoxy-2-amino-1-methyl-6-phenylimidazo[4,5-b]pyridine (N-OAc-PhIP). This case-control study was carried out to examine whether the genetic polymorphism of GSTA1 is associated with the risk oforal squamous cell carcinoma among Japanese people in relation to their smoking status. METHODS: In this study, 97 Japanese oral squamous cell carcinoma patients and 457 healthy controls were compared for the frequencies of theGSTA1 genotypes ((*) A:-567T,-69C,-52G,(*) B:-567G,-69T,-52A). RESULTS: The frequencies ofGSTA1 (*)A/(*)B+(*)B/(*) B genotypes were 32.3% in male cancer patients and 11.4% in female cancer patients, compared with 20.1% in the male control group (Odds ratio (OR)=1.86; 95% confidence interval (CI) 0.99-3.46) and 23.1% in the female control group (OR=0.58; 95% CI 0.18-1.81). TheGSTA1 (*)A/(*)B+(*)B/(*) B genotypes were associated with an 86% increased risk of oral squamous cell carcinoma among males, albeit without statistical significance. Also, among male smokers, the frequency ofGSTA1 (*)A/(*)B+(*)B/(*) B genotypes was significantly higher among the oral squamous cell carcinoma patients (33.3%) than among the controls (19.6%). The OR of the male smokers with theGSTA1 (*)A/(*)B+(*)B/(*) B genotypes for oral squamous cell carcinoma was 1.97 (95% CI 1.02-3.79). CONCLUSIONS: We present the first evidence of an association betweenGSTA1 (*) B and oral squamous cell carcinoma among smokers. This study suggests that the GSTA1 polymorphism and tobacco smoke-derived PhIP are associated with oral squamous cell carcinoma susceptibility among male smokers.