Relationship between genetic polymorphisms of alcohol and aldehyde dehydrogenases and esophageal squamous cell carcinoma risk in males

AIM： To investigate the association between the genetic polymorphisms of ADH2 and ALDH2, lifetime alcohol consumption and esophageal cancer risk in the Taiwan Residents men. METHODS： Between August 2000 and June 2003, 134 pathologically-proven esophageal squamous cell carcinoma male patients and 237 male controls were recruited from Kaohsiung Medical University Hospital and Kaohsiung Veterans General Hospital in southern Taiwan. ADH2 and ALDH2 polymorphisms were genotyped using PCR-RFLP. RESULTS： Compared to those with ADH2＊2/＊2, individuals with ADH2＊1/＊2 and ADH2＊1/＊1 had 2.28- and 7.14-fold, respectively, increased risk of developing esophageal cancer （95%CI = 1.11-4.68 and 2.76-18.46） after adjusting for alcohol consumption and other covariates. The significant increased risk was also noted among subjects with ALDH2＊1/＊2 （adjusted OR （AOR） = 5.25, 95%CI = 2.47-11.19）, when compared to those with ALDH2＊1/＊1. The increased risk of esophageal cancer was made greater, when subjects carried both ADH2＊1/＊1 and ALDH2＊1/＊2, compared to those with ADH2＊1/＊2 or ADH2＊2/＊2 and ALDH2＊1/＊1 （AOR = 36.79,95%a = 9.36-144.65）. Furthhermore, we found a multipticative effect of lifetime alcoholic consumption and genotypes （ADH2 and ALDH2） on esophageal cancer risk. CONCLUSION： Our findings suggest that polymorphisms of ADH2 and ALDH2 can modify the influence of alcoholic consumption on esophageal cancer risk.

Lack of correlation between p53 codon 72 polymorphism and anal cancer risk

AIM:To investigate the potential role of p53 codon 72 polymorphism as a risk factor for development of anal cancer. METHODS:Thirty-two patients with invasive anal carcinoma and 103 healthy blood donors were included in the study.p53 codon 72 polymorphism was analyzed in blood samples through polymerase chain reaction-restriction fragment length polymorphism and DNA sequencing. RESULTS:The relative frequency of each allele was 0.60 for Arg and 0.40 for Pro in patients with anal cancer, and 0.61 for Arg and 0.39 for Pro in normal controls. No significant differences in distribution of the codon 72 genotypes between patients and controls were found. CONCLUSION:These results do not support a role for the p53 codon 72 polymorphism in anal carcinogenesis.

Osteopontin is a promoter for hepatocellular carcinoma metastasis： a summary of 10 years of studies

In this review, we summarize the novel findings from our series of studies on the leading metastasis- related gene, osteopontin （OPN）. In our previous gene expression profiling study, OPN was identified as one of the leading genes associated with the metastasis of hepatocellular carcinoma （HCC）. We focused on OPN to evaluate its prognostic values and important roles in HCC metastasis. A retrospective study of large cohorts of HCC patients demonstrated that plasma OPN level was one of the leading independent prognostic factors for HCC patients, even in the early stage of HCC, and could serve as a surrogate serologic biomarker for monitoring the treatment response and tumor recurrence after HCC resection. Using both in vitro and in vivo investigations, we found that OPN has an important role in metastasis and tumor growth of HCC and is an attractive potential therapeutic target for combating HCC metastasis. We also found that OPNx HCC cells have much more amplifications at chromosomal regions, and promoter polymorphisms are important in the regulation of OPN expression and tumor growth and lung metastasis of HCC.