Identification of research needs to resolve the carcinogenicity of high-priority IARC carcinogens. views and expert opinions of an IARC/NORA expert group meeting, Lyon, France, 30 June - 2 July 2009, IARC technical publication no. 42. Lyon, France: International Agency for Research on Cancer, 2010 Jul; 42:99-106
An epidemiologic study that evaluates the association between acetaldehyde exposure and upper digestive tract cancer will require evaluation of all potential sources of exposure to acetaldehyde, to address their contribution to the overall risk. Different study designs could be proposed for such a study. Prospective studies could be designed to assess all sources of exposure using a combination of questionnaires and environmental and biological monitoring, as well as genotyping to identify individuals with ALDH2, ADH1C, and ADH1B deficiencies. However, given the long induction and latency of most cancers, such a study may not be feasible. Retrospective studies, conversely, have the limitation that exposures have to be evaluated retrospectively, increasing the potential for misclassification. Alternatively, acetaldehyde-derived DNA adducts could be used as biomarkers of exposure to acetaldehyde (Matsuda et al., 2006). On the other hand, there is substantial evidence that acetaldehyde, the first product of ethanol metabolism, is predominantly responsible for carcinogenesis of alcoholic beverages. Numerous epidemiologic studies in alcohol drinkers with ALDH2 deficiency or low ADH1B activity described above, strongly suggest that acetaldehyde derived from the metabolism of ethanol contributes towards causing upper digestive tract cancers. This notion is also supported by two meta-analyses that used a Mendelian randomization approach (Boccia et al., 2009) and a recent large-scale case-control study that reported a multiplicative combined risk for esophageal cancer among alcohol and tobacco consumers, who were low ADH1B and ALDH2-deficient carriers (Lee et al., 2008). The IARC Working Group that evaluated the carcinogenicity of alcoholic beverages (2007, Monograph 96) concluded that "acetaldehyde derived from the metabolism of ethanol in alcoholic beverages contributes to causing malignant esophageal tumors" (Baan, 2007). Furthermore, recent risk assessments that consider individual sources of exposure such as acetaldehyde in alcoholic beverages, acetaldehyde in saliva after alcohol drinking and cigarette smoking, acetaldehyde levels in foods and beverages such as yogurt, homemade beer and apples, have concluded that the lifetime cancer risks for many of these sources of exposure greatly exceed the usual limits for cancer risks from the environment (1:10(4)-1:10(6)). Acetaldehyde exposure is cumulative and in some cases synergistic (as occurs with alcohol exposure and smoking) (Salaspuro, 2009a). Exposure scenarios that consider multiple sources of exposure and genetic deficiencies in alcohol metabolism convey increased risks. It is thus recommended that the IARC classification of acetaldehyde is reviewed in a Monograph meeting.
Identification of research needs to resolve the carcinogenicity of high-priority IARC carcinogens. views and expert opinions of an IARC/NORA expert group meeting, Lyon, France, 30 June - 2 July 2009, IARC technical publication no. 42