2.1 Alcohol
Alcohol plays an important role in chronic pancreatitis.The proportion of chronic pancreatitis caused by alcohol varied across geographical regions.Between 32.6%and 95%of CP can be ascribed to alcoholism in the Western or Industrialized Asia-pacific region，and the percentage is between 18.8%and 41%in the developing Asia-pacific region（Table 3.2）.In China，the main etiology of CP in six health care areas of China was changed from biliary stone diseases to alcohol over 10 years（Wang et al.2009）.About 40%of CP was caused by alcohol in the six regions of China in the years between 2000 and 2003.
The incidence of alcohol chronic pancreatitis varied with gender.The results from the North American Pancreatitis Study-2（NAPS-2）showed that men（59.4%）were more likely than women（28.1%）to develop alcohol CP（Coté et al.2011）.The genome-wide association study found the variants in the CLDN2 gene loci could be associated with alcohol-related pancreatitis（Whitcomb et al.2012）.The higher frequency of homozygosity for this genetic variant in males（0.26）thanfemales（0.07）provided a possible explanation for the different gender distribution of CP.
Table 3.2 Percentage of patients with chronic pancreatitis in whom the cause is alcohol abuse（Reprint with permission from Jupp et al.2010）
Northern Europe comprises:Czech Republic，France，Germany，Poland，Switzerland，United Kingdom（Dite et al.2001；Levy et al.2006；Lankisch et al.2002b；Wehler et al.2004；Dzieniszewski et al.1990b；Ammann et al.1973；Gastard et al.1973；James et al.1974；Melia et al.1992）.Southern Europe comprises:Italy（Cavallini et al.1998；Frulloni et al.2009；Pezzilli et al.2007）
North and Central America comprises:USA，Mexico（Thuluvath et al.2003；Whitcomb et al.2008；Robles-Diaz et al.1990）.South America comprises:Brazil（Dani et al.1990）
Western/industrialised Asia-Pacific Region comprises:Australia，Japan，Singapore，South Korea（Otsuki and Tashiro 2007；Garg and Tandon 2004；Ishii et al.1973；Ryu et al.2005）
Developing Asia-Pacific Region comprises:China，India，Malaysia（Wang et al.2009；Garg and Tandon 2004；Balakrishnan et al.2008）.Africa comprises:French speaking African Nations，South Africa（Marks et al.1973；Moshal 1973；Uys et al.1973）(https://www.daowen.com)
Previous studies provide evidence supporting that there is a threshold effect and a doseresponse relationship between alcohol and CP（Irving et al.2009；Yadav et al.2009）.Compared with abstaining and light drinking，very heavy drinking was positively associated with CP（odds ratio，3.10；95%confidence interval，1.87-5.14）after controlling for age，sex，smoking status，and body mass index in the North American Pancreatitis Study-2.This study demonstrated that the risk of CP could be significantly increased for those who had five alcoholic drinks or more per day.（Yadav et al.2009）.A systematic review and meta-analysis of epidemiologic studies on the relationship between alcohol and pancreatitis found that there is not differences in the risk of pancreatitis between those consumed two or fewer drinks on average per day and nondrinkers（RR=1.0，95%CI:0.8-1.2；P=0.887）.Those who consumed three to four drinks per day had the higher risk of pancreatitis than the non-drinkers，but the difference was marginally slightly significant（RR=1.2，95%CI:1.0-1.5，P=0.059）.Compared with non-drinkers，the risk of pancreatitis was higher than those who consumed more than four drinks per day（RR=2.5，95%CI:2.0-3.1，P＜0.001）（Irving et al.2009）.
In addition，research found alcoholic CP was correlated with drinking age and daily consumption，but not the drinking frequency.The results from a survey conducted among male sobriety association members in Japan revealed that the drinking age was younger and the daily alcohol intake was greater among alcoholics with a history of pancreatitis than the alcoholics without pancreatitis（Maruyama and Otsuki 2007）.A study aiming to explore the relationship between pancreatitis and alcohol drinking habits showed drinking frequency may be not independently associated with pancreatitis（Kristiansen et al.2008）.Currently，the pathological mechanism of alcoholic chronic pancreatitis is unclear，and it is probable that chronic alcohol consumption sensitizes the acinar cell to injury（Pandol et al.2010）.