Esophageal cancer risk by ALDH2 and ADH2 polymorphisms and alcohol consumption: exploration of gene-environment and gene-gene interactions.

Alcohol drinking is a major risk factor for esophageal cancer in Japan and its impact may be modulated by levels of ALDH2, ADH2 and CYP2E1, three representative alcohol-metabolizing enzymes which display genetic polymorphisms altering individual alcohol-oxidizing capacity and drinking behavior. To assess the actual influence of ADH2 Arg47His, ALDH2 Glu487Lys and CYP2E1 variant c2 allele polymorphisms on esophageal cancer risk with conjunction with alcoholic consumption, the present 1:3 matched case-control study was conducted. The 165 histologically diagnosed Japanese esophageal cancer cases were here compared with 495 randomly selected controls, matched with respect to sex and age. Conditional logistic regression was used to calculated Odds Ratios (ORs) and 95% confidence intervals (95% CI). Significant gene-environment interactions between alcohol drinking and both ADH2 and ALDH2 were observed regarding esophageal cancer risk. The ADH2 Arg47His polymorphism showed moderately increased risk (OR for Arg/His and Arg/Arg relative to His/His: 2.01 (1.39-2.90)). In the ALDH2 case, comparing the Glu/Lys with the Glu/Glu genotype, ORs were markedly increased to 9.64 (3.23-28.8) and 95.4 (28.7-317) from 1.88 (0.42-8.37) and 4.62 (0.93-23.1) for moderate drinking and heavy drinking, respectively. No significant alteration in risk was observed with the CYP2E1 polymorphism. In conclusion, the present study revealed a significant gene-environment interaction between alcohol drinking and the ALDH2 polymorphism regarding esophageal cancer risk among a general population in Japan, providing concrete evidence of a role for acetaldehyde in neoplastic development. Interactions between ALDH2 and ADH2 need further clarification.

Comparison of lifestyle risk factors by family history for gastric, breast, lung and colorectal cancer.

To assess the theoretical impact of lifestyle of a cancer family history in first-degree relatives (CFH) and clarify interactions between CFH and lifestyle factors, hospital-based comparison and case-reference studies were conducted in Nagoya, Japan. Totals of 1988 gastric, 2455 breast, 1398 lung and 1352 colorectal cancer patients, as well as 50,706 non-cancer outpatients collected from 1988 to 1998, were checked for lifestyle factors, which included dietary and physical exercise habits, as well as smoking/drinking status. General lifestyle factors with non-cancer outpatients did not differ by the CFH status. Case-reference analyses showed that frequent intake of fruits, raw vegetables, carrots, pumpkin, cabbage and lettuce, as well as frequent physical exercise, were associated with decreased risk for all four sites of cancer, while habitual smoking increasing the risk of gastric, and more particularly, lung cancer. Interestingly, the study revealed the magnitude of odds ratios for the above lifestyle factors obtained from CFH positives to be similar to those from CFH negatives for these four sites of cancer. There were no significant interactions between CFH and any particular lifestyle factor. In conclusion, our results suggest no appreciable influence of CFH on lifestyle related risk factors for gastric, breast, lung, and colorectal cancer. Habitual smoking increased, while frequent physical exercise and raw vegetables intake decreased cancer risk, regardless of the CFH status.

A pilot study on genotype announcement to induce smoking cessation by Japanese smokers.

BACKGROUND: Genotype announcements related to susceptibility to hazardous effects of smoking may be effective to induce smoking cessation. METHODS: Subjects were municipal government employees, 63 young smokers employed in the previous year and 59 smokers with more than 45 pack-years, who were invited to educational sessions against smoking held in December 2003 and February 2004, respectively. In the session, those who wished genetic susceptibility tests (GSTM1, GSTT1, and NQO1 C609T) were enrolled in the study. The smoking habit was ascertained three times: at the session, one month later, just before the genotype announcement, and at the follow-up three months after the announcement. RESULTS: Fifty eight (92.1%) and 49 (83.1%) smokers participated in the study, respectively. One out of 58 smokers was not a habitual smoker, so was not included in the analysis. The smoking cessation rates were 15.8% (9 participants) and 6.1% (3 participants) just before the genotype announcement, and 7.0% (4 participants) and 10.2% (5 participants) at the follow-up, respectively. All subjects were satisfied with the genotype testing except for two who rather regretted participating, but one of whom actually quit smoking. CONCLUSION: The present pilot study without controls indicated that the effects of genotype announcements in this framework on smoking cessation were less than might have been expected. The temporary effect of the session on younger smokers may have been due to the participation per se. The potential effects of genotype announcements for heavy smokers should now be examined in studies with adequate controls.

Estimation of cancer incidences in Aichi prefecture: use of a model area with good quality registry data.

In Japan, local government is responsible for organization of population-based cancer registries and the quality of the registration remains modest, mainly due to dependence on voluntary-based operations without legal obligations. Aichi Prefecture cancer registry covers a large population, estimated at 7 million, and its quality has yet to reach the level required internationally. The derived cancer incidences for Aichi Prefecture therefore tend to be underestimated. In the present study we set up a model area, located in the central part of Aichi Prefecture, with a good quality of registry data, covering a reasonable population, including both urban and rural areas. Our model area has typical demographic features of Aichi Prefecture. The materials were data on cancer incidence and deaths during the period of 1996-2000 in this model area of Aichi prefecture, with a population of approximately one million, under the jurisdiction of three public health centers, covering nine municipalities. The percentage of death certificated notified (DCN) cases for all sites was around 14% and the incidence/death ratio was around 1.9. Estimated age-adjusted incidence rates were found to be 256.0 (per 100,000) for males and 177.6 for females, these values being 10-15 % higher than those generated using data for the whole prefecture, and quite close to incidence rates in Japan estimated from the highest quality of data available. It is suggested that the cancer incidence in the Aichi prefecture is indeed being underestimated and that the actual figures may be closer to the estimates provided here.

Different risk relations with smoking for non-small-cell lung cancer: comparison of TP53 and TP73 genotypes.

BACKGROUND: The association between TP53/TP73 gene polymorphisms and tobacco smoking was evaluated with regard to risk of non-small cell lung cancer (NSCLC). METHODS: A case-control study with 192 histologically confirmed NSCLC cases and 241 non-cancer controls was conducted. Subjects were genotyped for TP53 Arg72Pro and TP73 G4C14 to A4T14 polymorphisms by PCR-based methods. Risk and interactions were assessed as odds ratios (ORs) and 95% confidence intervals (CIs). RESULTS: The analyses according to TP53 genotypes for the risk of tobacco smoking illustrated that risk with heavy smoking was much higher for subjects with the TP53 ProPro genotype (OR: 16.4, 95% CI 1.77-151.7) as compared with those with TP53 ArgArg/ArgPro (3.36, 1.69-6.68). Similar analyses for TP73 genotypes did not show any differences for NSCLC risk. CONCLUSION: A risk relation of heavy smoking for the NSCLC is suggested with the TP53 but not the TP73 polymorphism.