Baseline alcohol consumption, type of alcoholic beverage and risk of colorectal cancer in the European Prospective Investigation into Cancer and Nutrition-Norfolk study
Introduction
Colorectal cancer (CRC) was the third most common cancer worldwide after lung and breast cancer in 2002, and the second most common incident form of cancer in Europe in 2006 [1]. Around 100 new cases of CRC were diagnosed each day in the United Kingdom (UK) in 2004, and it is also the second major cause of cancer death in the country and with almost equal distribution between men and women [2].
Excessive alcohol intake is associated with increased risk of cancers of the mouth, pharynx, and larynx, and oesophagus, all of which are in direct contact with ingested alcohol [3]. According to the latest evaluation by the International Agency for Research on Cancer (IARC), colorectal cancer (CRC) has also been added to the list of alcohol-related malignancies [4]. Evidence of a positive association between alcohol intake and risk of cancer has mostly related to men with high alcohol consumption, with the exception of breast cancer which has been positively associated with moderate alcohol intake in women [5]. Previous meta-analyses reported a 38% increased risk for cancer of the colorectum [6], and 21% and 42% increased risk for cancer of the colon and rectum, respectively [7] with 100 g of daily alcohol intake. However, the latest report and meta-analysis from the World Cancer Research Fund and American Institute for Cancer Research concluded based on nine cohort studies published up to year 2005 that an excessive consumption of ethanol from alcoholic drinks, more than 30 g/day, is a convincing cause of CRC in men and probable cause in women [3].
Nevertheless, recent evidence from population-based prospective studies on the relationship between CRC risk and total alcoholic drinks or total alcohol consumption has been inconsistent with some, but not all, studies supporting a non-significant, modest magnitude of association with less than 30 g/day [5], [8], [9], [10], [11], [12], [13], [14], [15]. Moreover, the associations between consumption of specific alcoholic beverages on overall and site-specific CRC risk have not been well investigated and very limited evidence from prospective studies is currently available [5], [8], [9], [10], [11]. There has also been a weak suggestion of a ‘J’-shaped dose–response relationship with CRC risk [3], similar to the accepted association between moderate alcohol consumption and a lower risk for cardiovascular morbidity and mortality [16], however, few studies have shown this for CRC [17], [18] and results have been inconsistent.
The mechanism by which alcohol influences CRC risk remains less well understood [19]. Hypotheses which have been postulated include: a carcinogenic effect of chemicals such as N-nitrosamines other than ethanol present in alcoholic beverages; a solvent action which facilitates absorption of other carcinogens, e.g. those in tobacco smoke; and a carcinogenic and genotoxic role for acetaldehyde, the major metabolite of ethanol and changes in folate metabolism [3], [20].
In the UK, alcohol is an accepted part of the social fabric. However, the UK annual alcohol consumption in 2003 now exceeds the European Union average [21] and the number of people with incident CRC exceeds 36,000 people annually in the UK in 2004 [2]. Hence, even a moderate excess risk may have important public health implications, and it is important to clarify the association between alcohol consumption and CRC risk in a general population.
The aim of this study was therefore to determine the relationship between total alcohol consumption or consumption of specific types of alcoholic beverages on overall and site-specific colorectal cancer risk in a British population, using the UK Norfolk arm of the European Prospective Investigation into Cancer and Nutrition (EPIC) study.
Section snippets
Study population
The participants in this study were part of a prospective population study of 25,639 individuals (11,607 men and 14,032 women) aged between 40 and 79 years who were residing in Norfolk, United Kingdom. The design and study methods have been described previously [22]. Briefly, the cohort was recruited between 1993 and 1997 from age-sex registers of general practices (which, because of the UK National Health Service, serve as a population register) as part of a ten-country collaborative study,
Results
A total of 407 CRC cases (224 male and 183 female cases, average 64 years old) were identified in 24,244 participants over 273,826 person-years, over an average of 11 years of follow-up of the EPIC-Norfolk cohort. Of these cancers, 270 were located in the colon (144 male and 126 female cases, average 64 years old) and 129 were located in the rectum (73 male and 56 female cases, average 63 years old).
Table 1 presents the baseline characteristics of the participants according to alcohol drinking
Discussion
In this large population-based cohort, we investigated the associations between total alcohol consumption, consumption of specific types of alcoholic beverages and the risk of cancers of the colorectum, the colon, or the rectum. When compared with non-drinkers, we found that the usual observed range of alcohol drinking, from 0.5 to 21 units/week (∼>0 and <24 g/day), was not overall associated with an increased CRC risk. Multivariate adjustment did not change these observations. Sensitivity
Conflict of interest statement
None declared.
Acknowledgements
We thank all the participants and the entire EPIC-Norfolk team. The EPIC-Norfolk cohort is supported by grant funding from Cancer Research UK and the Medical Research Council.
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Professor Rodwell (Bingham) read an initial draft of this manuscript, but sadly passed away between submission and acceptance of this article.