1、Environmental Health PerspectivesVOLUME116|NUMBER2|February 2008231ResearchArsenic is a ubiquitous element in the envi-ronment,where it occurs in both organic andinorganic forms;it can be found in food,water,soil,and airborne particles,andhumans are widely exposed through thesesources(Tchounwou et a
2、l.2004).Arsenic cancause fatal acute poisoning,and long-termexposure has been associated with variouscancers,diabetes,skin disease,chronic cough,and toxic effects in the liver,kidney,cardio-vascular system,and the peripheral and cen-tral nervous systems(Vahter et al.2006).Organic arsenic,which is le
3、ss harmful thanthe inorganic forms,is most abundant infood,whereas inorganic arsenic compoundsare found mainly in aquifers(Abernathy et al.2003),where they accumulate by naturalprocesses such as weathering,erosion,and biological activity,or eventually fromanthropogenic contamination(Smedley andKinni
4、burgh 2005).Consequently,mosthealth-related problems associated witharsenic are derived from groundwater used fordrinking(Farago et al.1997;Smedley andKinniburgh 2005).Epidemiologic studies in Asia(Chen et al.1986,1988;Tsuda et al.1995;Wu et al.1989)and Latin America(Ferreccio et al.2000;Hopenhayn-R
5、ich et al.1996,1998;Marshall et al.2007)have shown that higharsenic concentrations(up to several hundredmicrograms per liter)in drinking-water areassociated with various internal cancers andwith cancer of the skin.Some of these studiesalso provide evidence of a doseresponse rela-tion(Chen et al.1986
6、,1988;Wu et al.1989).However,few studies,most of whichwere conducted in the United States,haveaddressed the adverse effects of exposure tolow doses of arsenic,and their results areinconsistent.Some showed a positive associa-tion between relatively low doses of arsenicand cancers of the skin,prostate
7、,and bladder(Knobeloch et al.2006;Kurttio et al.1999;Lewis et al.1999),whereas others showed nosuch effects(Bates et al.1995;Karagas et al.2001;Steinmaus et al.2003).One studyshowed a nonsignificant decreasing risk forbladder cancer with increasing exposure toarsenic in the range of 360 g/L(Lammet a
8、l.2004),and Karagas et al.(2002)founda U-shaped doseresponse relation betweenexposure to arsenic and non-melanoma skincancer,with a decreased risk at low levels andincreased risk at higher levels.The existenceof a threshold for the carcinogenic effect ofarsenic has been debated,especially in theUnit
9、ed States(Abernathy et al.1996;Schoenet al.2004),and some studies have suggestedan interaction between exposure to arsenicand smoking in the causation of cancers ofthe lung,bladder and skin(Bates et al.1995;Ferreccio et al.2000;Knobeloch et al.2006;Steinmaus et al.2003;Tsuda et al.1995).Recent anima
10、l models for inorganicarsenic carcinogenesis suggest that the carcino-genicity of arsenic involves several mecha-nisms and co-exposure to other carcinogens(Burns et al.2004;Cohen et al.2007;Rossman et al.2004;Waalkes et al.2007;Wanibuchi et al.2004).In vitro low concen-trations of arsenic protected
11、against oxidativestress and DNA damage(Snow et al.2005),in accordance with the results of some of theepidemiologic studies(Karagas et al.2002;Lamm et al.2004).More studies are needed,however,to evaluate the possible carcinogeniceffect of exposure to low concentrations ofarsenic.The aim of this large
12、,population-based cohort study was to determine if indi-vidual exposure to low levels of arsenic indrinking-water in Denmark is associated witha risk for cancer.Materials and MethodsStudy population.The study was based onthe prospective Danish cohort Diet,Cancerand Health,which has been described in
13、detail elsewhere(Tjnneland et al.2007).Inbrief,160,725 persons 5064 years of ageand living in one of 23 municipalities in theCopenhagen or Aarhus area were invited toparticipate.Of these,57,053 persons(27,178men and 29,875 women)accepted the invita-tion and were enrolled between 1993 and1997.At enro
14、llment,information was col-lected including on diet,beverages,smoking,education,medical conditions,occupations,reproductive factors,body mass index,andskin reaction to sun.The study“Diet Cancerand Health”has been approved by the rele-vant Scientific Committees and the DanishData Protection Agency.In
15、formed consentwas obtained from all participants to searchinformation from medical registers includingthe Danish Cancer Registry.Address correspondence to R.Baastrup,DanishCancer Society,Institute of Cancer Epidemiology,Strandboulevarden 49,DK-2100 Copenhagen,Denmark.Telephone:45 35 25 76 86.Fax:45
16、3525 77 31.E-mail:baastrupcancer.dkA scholar grant from the Medical and ScientificCommittee at the Danish Cancer Society fundedthis study.The authors declare they have no competingfinancial interests.Received 2 July 2007;accepted 23 November2007.Arsenic in Drinking-Water and Risk for Cancer in DenmarkRikke Baastrup,1Mette Srensen,1Thomas Balstrm,2Kirsten Frederiksen,1Carsten Langtofte Larsen,3Anne Tjnneland,1Kim Overvad,4and Ole Raaschou-Nielsen11Danish Cancer Society,Institute of Cancer Epidemi
