Alcohol dehydrogenase and aldehyde dehydrogenase gene polymorphisms, alcohol intake and the risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition study

BACKGROUND/OBJECTIVES: Heavy alcohol drinking is a risk factor of colorectal cancer (CRC), but little is known on the effect of polymorphisms in the alcohol-metabolizing enzymes, alcohol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) on the alcohol-related risk of CRC in Caucasian populations. SUBJECTS/METHODS: A nested case-control study (1269 cases matched to 2107controls by sex, age, study centre and date of blood collection) was conducted within the European Prospective Investigation into Cancer and Nutrition (EPIC) to evaluate the impact of rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms on CRC risk. Using the wild-type variant of each polymorphism as reference category, CRC risk estimates were calculated using conditional logistic regression, with adjustment for matching factors. RESULTS: Individuals carrying one copy of the rs1229984(A) (ADH1B) allele (fast metabolizers) showed an average daily alcohol intake of 4.3 g per day lower than subjects with two copies of the rs1229984(G) allele (slow metabolizers) (P-diff<0.01). None of the polymorphisms was associated with risk of CRC or cancers of the colon or rectum. Heavy alcohol intake was more strongly associated with CRC risk among carriers of the rs1573496(C) allele, with odds ratio equal to 2.13 (95% confidence interval: 1.26-3.59) compared with wild-type subjects with low alcohol consumption P-((interaction)=0.07). CONCLUSIONS: The rs1229984(A) (ADH1B) allele was associated with a reduction in alcohol consumption. The rs1229984 (ADH1B), rs1573496 (ADH7) and rs441 (ALDH2) polymorphisms were not associated with CRC risk overall in Western-European populations. However, the relationship between alcohol and CRC risk might be modulated by the rs1573496 (ADH7) polymorphism. European Journal of Clinical Nutrition (2012) 66, 1303-1308; doi: 10.1038/ejcn.2012.173; published online 14 November 201

What can molecular pathology contribute to the management of renal cell carcinoma?

The incidence of renal cell carcinoma (RCC) is increasing and outcomes remain poor. One-third of patients with localized disease will relapse, and 5-year survival for patients with metastatic disease is less than 10%. No molecular test is currently available to identify which patients who have undergone 'curative' surgery will relapse, and which patients will respond to targeted therapy. Some well characterized biochemical pathways, such as those associated with von Hippel-Lindau disease, are aberrantly regulated in RCC and are associated with histological subtype, but the understanding of these pathways contributes little to the clinical management of patients with RCC. Gene expression and sequencing studies have increased our understanding of the genetic basis of the disease but have failed to establish any unified classification to improve molecular stratification or to predict which patients are likely to relapse or respond to targeted therapy. Instead, they have served to highlight that RCC is heterogeneous at histological, morphological, and molecular levels, and that novel approaches are required to resolve the complexity of RCC prognostication and prediction of treatment response.</p