Alcohol Drinking and Liver Cancer Risk

23 Pages·2008·0.18 MB·English

Jpn J Clin Oncol 2008;38(12)816–838
doi:10.1093/jjco/hyn108
Alcohol Drinking and Liver Cancer Risk: An Evaluation Based
on a Systematic Review of Epidemiologic Evidence
among the Japanese Population
Keitaro Tanaka1, Ichiro Tsuji2, Kenji Wakai3, Chisato Nagata4, Tetsuya Mizoue5, Manami Inoue6
and Shoichiro Tsugane6, for the Research Group for the Development and Evaluation of Cancer Prevention
Strategies in Japan†
1Department of PreventiveMedicine,Facultyof Medicine, Saga University, Saga,2Division of Epidemiology,
D
Department of Public Health and Forensic Medicine, Tohoku University Graduate School of Medicine, Sendai, o
w
3Department of PreventiveMedicine/Biostatistics and MedicalDecisionMaking,Nagoya UniversityGraduate School n
lo
of Medicine, Nagoya, 4Department of Epidemiologyand PreventiveMedicine, Gifu University Schoolof Medicine, ad
e
Gifu, 5Department of Epidemiologyand International Health, ResearchInstitute, International Medical Centerof d
Japan,Tokyoand6Epidemiologyand Prevention Division, ResearchCenterforCancer Prevention and Screening, fro
m
National Cancer Center, Tokyo, Japan h
ttp
s
ReceivedJuly6,2008;acceptedSeptember15,2008;publishedonlineOctober22,2008 ://a
c
a
d
e
Background: Although alcohol consumption has been recognized as a risk factor for primary m
ic
liver cancer, it will be informative to summarize relevant epidemiologic data in the Japanese .o
u
who have characteristic environmental determinants (e.g. hepatitis C virus infection) and p.c
genetic traits (e.g. presence of pooracetaldehydemetabolizers). om
Methods: We systematically reviewed epidemiologic studies on alcohol drinking and liver /jjc
o
cancer among Japanese populations. Original data were obtained through searches of the /a
MEDLINE (PubMed) and Ichushi databases, complemented with manual searches. The rtic
le
evaluation was performed in terms of the magnitude of association (‘strong’, ‘moderate’, -a
b
‘weak’ or‘no association’)in eachstudyand the strength of evidence (‘convincing’, ‘probable’, stra
‘possible’ or ‘insufficient’), together with biological plausibility as previouslyassessed by the ct/3
International Agencyfor Research onCancer. 8
/1
Results: Among 22 cohort studies identified, 14 (64%) reported weak to strong positive 2
/8
associations between alcohol and livercancer risk, 3 (14%) reported no association and five 16
(23%) reported weakto moderate inverse associations; such inverse associations werefound /87
7
mostly in follow-up studies of patients with chronic liver disease (particularly, cirrhotic 97
7
patients), yet recent studies on patients with chronic hepatitis C presented fairly consistent b
y
positive associations. Of 24 case–control studies identified, 19 (79%) showed weak to strong g
u
positive associations, whereasthe remainder demonstrated no association (n¼4) ora mod- es
erate inverse association (n¼1). t on
Conclusion: We conclude that there is ‘convincing’ evidence that alcohol drinking increases 08
A
theriskof primary livercanceramong theJapanese population. p
ril 2
0
Keywords: systematic review – epidemiology – alcohol – livercancer – Japanese 1
9
INTRODUCTION injury that can lead to enhanced fibrosis and eventually to
liver cirrhosis through various mechanisms presumed (1).
Alcohol has long been viewed as a hepatotoxic agent, and
Alcohol drinking has also been implicated in the etiology
its heavy consumption is known to cause hepatocellular
of primary liver cancer that often develops from cirrhosis
(2). In the most recent evaluation by the International
Agency for Research on Cancer (IARC), the occurrence of
Forreprintsandallcorrespondence:KeitaroTanaka,Departmentof
PreventiveMedicine,FacultyofMedicine,SagaUniversity5-1-1 liver cancer has been ‘causally’ related to the consumption
Nabeshima,Saga849-8501,Japan.E-mail:[email protected]
†ResearchgroupmembersarelistedintheAppendix.
#TheAuthor(2008).PublishedbyOxfordUniversityPress.Allrightsreserved.
JpnJ Clin Oncol 2008;38(12) 817
of alcoholic beverages (3). In the second report published (SS) or RR.2.0 (SS); (ii) ‘moderate’ (symbol ## or "")
by the World Cancer Research Fund and the American when RR,0.5 (NS), 0.5(cid:3)RR,0.67 (SS), 1.5,RR(cid:3)
Institute for Cancer Research, the Panel has judged that 2.0 (SS) or RR.2.0 (NS); (iii) ‘weak’ (symbol #or ")
alcohol consumption is ‘probably’ a direct cause of liver when 0.5(cid:3)RR,0.67 (NS), 0.67(cid:3)RR(cid:3)1.5 (SS) or
cancer (4). 1.5,RR(cid:3)2.0 (NS) and (iv) ‘no association’ (symbol 2)
Primary liver cancer is one of the most common cancers when 0.67(cid:3)RR(cid:3)1.5 (NS); the RR used in this paper
in Japan (5). More than 90% of primary liver cancers in denotes ratio measures of effect, including risk ratios, rate
this country are hepatocellular carcinomas (HCCs) that are ratios, hazard ratios and odds ratios. When RRs for three or
mostly attributable to chronic infections with hepatitis C more exposure levels were reported, that for the highest level
virus (HCV) and hepatitis B virus (HBV) (6,7); HCV and was employed for this classification. In the case of multiple
HBV infections are estimated to account for 70 and 15%, publications of analyses of the same or overlapping data
respectively, of the recent occurrences of HCC in Japan (6). sets, only datafrom the largest or most updated results were D
o
w
This tendency clearly contrasts with the situation in south- included. Studies that reported RRs for indefinite exposure n
lo
east Asia and sub-Saharan Africa where HBV represents a levels, or did not provide RRs or data necessary for the a
d
dominant risk factor of HCC, and with that in Western present authorstocalculaterelevant RRs, were excluded. ed
countries where HCV infection plays an increasingly After this process, the strength of evidence was evaluated fro
m
important role (2,8). The role of alcohol in hepatocarcino- in a manner similar to that used in the WHO/FAO Expert h
genesis might differ between Japan and such areas. Consultation Report (12), in which evidence was classified ttp
s
Moreover, (cid:2)50% of the Japanese are poor metabolizers of as ‘convincing’, ‘probable’, ‘possible’ and ‘insufficient’. We ://a
c
acetaldehyde (9), the first metabolite of ethanol, which has assumed that biological plausibility corresponded to the a
d
e
been recognized as being possibly carcinogenic to humans judgment of the most recent evaluation from the IARC (3). m
ic
(10). Such poor metabolizers have not been found in Despite the use of this quantitative assessment rule, an arbi- .o
u
Africans or Caucasians (9), and thus the Japanese as traryassessment cannot be avoided when considerable varia- p
.c
Mongoloids might be more susceptible to alcohol than tion exists in the magnitudes of association among the om
other ethnic groups. results of each study. The final judgment, therefore, was /jjc
o
The aim of the present study was to review and summar- made based on a consensus of the research group members, /a
ize epidemiologic findings on alcohol drinking and liver and it was therefore not necessarily objective. When we rtic
le
cancer among Japanese populations. This work was con- reach a conclusion that there is ‘convincing’ or ‘probable’ -a
b
ducted as part of a project of systematic evaluation of the evidence of an association, we conduct a meta-analysis to stra
epidemiologic evidence regarding lifestyles and cancers in obtain summary estimates for the overall magnitude of c
t/3
Japan (11). association. 8
/1
2
/8
1
PATIENTS AND METHOD 6/8
MAIN FEATURES AND COMMENTS 77
The details of the evaluation method have been described 9
7
7
elsewhere (11). In brief, original data for this review were We identified a total of 22 cohort (13–34) (Table 1) and 24 b
y
identified through searches of the MEDLINE (PubMed) and case–control studies (35–58) (Table 2). Of those cohort g
u
Ichushi (Japana Centra Revuo Medicina) databases, comple- studies, two presented the results by sex (19,31), seven for e
s
mented by manual searches of references from relevant men only (13–16,26,29,32) and 13 for men and women t o
n
articles where necessary. All epidemiologic studies on the combined (17,18,20–25,27,28,30,33,34). The respective 0
8
association between alcohol drinking and liver cancer inci- numbers for the case–control studies are two (45,54), nine Ap
dence/mortalityamong the Japanese from 1950 (or 1983 for (36–38,42,44,48–51) and 13 (35,39–41,43,46,47,52,53,55– ril 2
0
the Ichushi database) to June 2008, including papers in press 58). Several studies showed the results separately according 1
9
if available, were identifiedusing the following as keywords: to studyareas (16), different age categories (31),the severity
alcohol, liver, hepatocellular, cohort, follow-up, case– of chronic liver disease (CLD) (33) or different control
control, Japan and Japanese. Papers written in either English groups (49,54,56).
or Japanese were reviewed, and only studies on Japanese Study populations in the cohort studies, except for one
populations living in Japan were included. The individual study based on male alcoholics (26), were classified broadly
results were summarized in the tables separatelyas cohort or into two categories: mostly healthysubjects (n¼7) such as
case–control studies. local residents (14,16,25,31,32), physicians (13) and atomic
The evaluation was made based on the magnitudes of bombsurvivors(19)andpatientswithCLD(15,17,18,20–24,
association and the strength of evidence. First, the former 27–30,33,34) (n¼14) (Table 1). Chronic infections with
was assessed by classifying the relative risk (RR) in each both HCV and HBV were taken into account in 12 studies,
study into the following four categories, while considering all of which followed patients with CLD (18,20–24,
statistical significance (SS) or no statistical significance 27–30,33,34). In the case–control studies, excluding one
(NS): (i) ‘strong’ (symbol ### or """) when RR,0.5 study based on military men exposed to thorotrast (38), a
Table1. CohortstudiesonalcoholdrinkingandlivercanceramongJapanese 8
1
8
Reference Study Studypopulation Category Number Relativerisk Pfor Confoundingvariables Comments
period among (95%CI trend considered
cases orP)
Numberof Sourceofsubjects Event Numberof A
subjects followed incidentcases lc
o
for ordeaths h
o D
analysis l o
d w
r n
Konoetal. 1965– 5130men Malephysiciansinwestern Death 51men Never/past 1.00 Age,smoking HBsAgandanti-HCVwere in lo
(13) 83 Japan (u4pn2rs)ipmeacrifiye9d, O,c2cagsoi/odnaayl 121...893084)((00..8601–– nottested. kingand aded from
(cid:4)2go/day 425...033256))(1.04– liverca https://ac
n a
Hirayama 1966– 122261 95%ofthecensus Death 788men Forlivercancer Age HBsAgandanti-HCVwere c d
e e
(14) 82 men populationin29 (livercancer) nottested r m
hineaslitxh-pcreenfetecrt-ucroevseredareas o(prr1im23armyelniver NDoaitlydaily 11..0205 risk ic.ou
p
cancer) (P,0.01) .c
o
m
Fliovrerpcriamncaeryr /jjc
o
/a
Notdaily 1.00 rtic
Daily 1.89 le
(P,0.01) -ab
s
Inabaetal. 1973– 270men Patientswithlivercirrhosis Death 46men Never 1.00 Age,HBsAg,histories Anti-HCVwasnottested tra
c
(15) 88 atJuntendoUniversity Current/past 0.41(0.08– ofbloodtransfusion, t/3
Hospital hepatitisandsurgical 8
2.20) operation,smoking /12
/8
Shibata 1958– 639men Residentsinafarmingarea Death 11men Farmingarea 1
6
etal.(16) 86 ina orafishingareainKyushu (farming /8
Non-drinker 2 1.0 .0.1 Age HBsAgandanti-HCVwere 7
farming area)and22 7
nottested 9
areaand men(fishing Sake,1go/ 6 1.1(0.2– 7
7
677men area) day 5.5) b
ina Sake1–2go/ 2 1.6(0.2– y g
fishing u
day 11.6) e
area s
Sake(cid:4)2go/ 1 1.1(0.1– t on
day 13.5) 0
8
Fishingarea Ap
Non-drinker 2 1.0 Age ril 2
0
1
Sake,1go/ 0 – 9
day
Sake1–2go/ 0 –
day
Sake(cid:4)2go/ 1 5.5(0.6–
day 51.1)
Fishingarea
Shochunone 4 1.00 ,0.01 Age,smoking
Shochu,2go/ 14 5.85(1.31–
day 26.18)
Shochu(cid:4)2go/ 4 14.02
day (2.34– D
83.89) o
w
n
Katoetal. 1987– 1784 Patientswith Incidence 122 Neverdrinker 46 1.00 Sex,age HBsAgandanti-HCVstatus lo
a
(17) 90 decompensatedliver wasunknown.Thetotal d
Pastdrinker 19 0.58(0.32– e
cirrhosisorpost-transfusion alcoholindexwasobtained d
hepatitis 1.04) bymultiplyingthedaily fro
Occasional 4 0.43(0.15– ethanolintake(ml)bythe m
drinker 1.24) numberofyearsofdrinking http
Currentdrinker 5 01..4061)(0.16– s://a
c
a
Totalalcohol de
index m
ic
0 46 1.00 0.046 .ou
p
1–1999 10 0.49(0.23– .c
o
1.02) m
2000þ 13 0.53(0.27– /jjco
1.04) /a
rtic
Tsukuma 1987– 917(548 Patientswithchronic Incidence 54 Nondrinker 1.00 Age,sex,stageof HBsAgandanti-HCVstatus le
etal.(18) 91 menand hepatitisorcompensated disease,serum wasadjustedfor. -a
Occasional 0.77(0.20– b
369 cirrhosisatCenterforAdult alpha-fetoprotein, s
women) Diseases,Osaka drinker 2.99) HBsAg,anti-HBc, tra
c
Formerdrinker anti-HCV,smoking t/3
8
,80g 1.46(0.56– /1
2
ethanol/day 3.79) /8
1
(cid:4)80g 1.66(0.69– 6/8
ethanol/day 3.96) 7
7
9
Currentdrinker Jpn 77 b
,80g 1.10(0.39– y
ethanol/day 3.07) JC gu
e
(cid:4)80g 1.15(0.35– lin st o
ethanol/day 3.78) O n
n 0
Goodman 1980– 36133 Atomicbombsurvivors Incidence 242(156men Formen Sex,city,ageatthetime HBsAgandanti-HCVwere co 8 A
etal.(19) 89 and86 ofbombing,age, nottested. l p
women) Never-drinker 25 1.00 radiationdosetothe 200 ril 2
Ever-drinker 126 11..1701)(0.72– liver 8;3 019
8
(
Ex-drinker 25 2.33(1.34– 1
2
4.07) )
Quit(cid:4)16 4 0.96(0.33–
yearsago 2.77)
8
1
Continued 9
Table1. Continued
8
2
0
Reference Study Studypopulation Category Number Relativerisk Pfor Confoundingvariables Comments
period among (95%CI trend considered
cases orP)
Numberof Sourceofsubjects Event Numberof A
subjects followed incidentcases lc
for ordeaths oh
analysis o D
l o
d w
Quit11–15 8 2.08(0.93– r n
in lo
yearsago 4.67) k a
in de
Quit(cid:3)10 12 7.87(3.89– g d
yearsago 16.0) and from
Pwree,eske1n3t5dmrinl/ker 13070 0111....09582918))((00..6635–– livercan https://aca
c d
135–299ml/ 37 1.11(0.67– er em
we(cid:4)ek300ml/ 37 11..8162)(0.67– risk ic.oup
week 1.87) .c
o
m
Forwomen /jjc
o
Never/past 56 1.00 /a
drinker rtic
Presentdrinker 27 1.25(0.78– le-a
1.98) b
s
,27ml/week 1 0.28(0.04– tra
c
2.02) t/3
8
27–69ml/ 6 1.20(0.52– /1
2
week 2.79) /8
1
(cid:4)70ml/ 9 2.02(0.99– 6/8
week 4.09) 7
7
9
Chibaetal. 1977– 412(249 Patientswith Incidence 63(54men Nondrinker 1.00 Sex,age,stageof Allsubjectswere 7
7
(20) 93 menand HCV-associatedchronic and9 disease,serum anti-HCV-positiveand b
,150kg 1.33(0.60– y
1w6o3men) hcierprhatoistiissoatrTcosmukpuebnasated women) ethanol 2.93) aalnpthi-aH-fBesto,parnottie-HinB,c, HBsAg-negative. gue
UniversityHospital 1et5h0a–no4l49kg 13..5107)(0.71– htriasntosfruiessioonf,bsluorogdical st on
procedureandliver 0
(cid:4)450kg 0.98(0.43– cancerinfamily, 8 A
Ikedaetal. 1980–? 2215 Patientswithchronic Incidence 89 Aetlhlasnuobljects (n¼2215) 2.23) Ssmtaogkeinogfhepatitis, HBsAgandanti-HCVstatus pril 20
1
(21) (1544men hepatitisatToranomon gamma-glutamyl wasavailableforall 9
,500kg 1.00
and671 Hospital transpeptidase subjects.
ethanol
women)
(cid:4)500kg 3.04(1.79–
ethanol 5.14)
HBsAg(þ) (n¼610) Indocyaninegreen
anti-HCV(2) retentionrate
subjects
,500kg 1.00
ethanol
(cid:4)500kg 8.37(2.70–
ethanol 25.93)
HBsAg(2) (n¼1500) Stageofhepatitis,
anti-HCV(þ) g-glutamyl
subjects transpeptidase,history D
o
ofbloodtransfusion, w
,500kg 1.00 n
ethanol albumin loa
d
e
(cid:4)500kg 1.96(1.06– d
ethanol 3.62) fro
m
Tanaka 1985– 96(62 Patientswithlivercirrhosis Incidence 37(27men Never 16 1.00 Sex,age,yearssinceLC HBsAgandanti-HCVstatus h
etal.(22) 95 m3w4oemneann)d aHtoKspyiutaslhuUniversity awnodm1e0n) Past 17 01..5793)(0.20– dhseoiarsugpmnitoasaliilszb,audtmieoipnna,srttAmatSueTsn,,t, wrdeealsasctiravidbejeurdsistiekndstwfhoeerr.oeTrinhgoeitnal ttps://a
c
Current alpha-fetoprotein, paper,andwerereestimated ad
HBsAg,anti-HCV, byoneoftheauthors(KT). e
,2.4drinks/ 1 0.06(0.01– m
day 0.57) smoking O23nem‘ldorfinekt’hacnoorrle.spondsto ic.o
u
(cid:4)2.4drinks/ 3 0.17(0.02– p.c
day 1.42) o
m
Matsushita 1985– 267(165 Patientswithlivercirrhosis Incidence 67 TypeBorC (n¼202) Age,anti-HCV Allsubjectsanalyzedwere /jjc
etal.(23) 94 menand atKanazawaUniversity cirrhosis positiveforanti-HCVor o/a
1w0o2men) Hospital Pdroisniktiivneg 13..8336)(1.00– HBsAg. rticle-a
history b
s
TypeC (n¼140) Age tra
c
cirrhosis t/3
8
Positive 2.36(1.23– /1
2
drinking 4.54) /8
history 1
6
/8
Aizawa 1981– 153(115 Patientswithchronic Incidence Notdescribed Habitualheavy Sex,age,ALT, Allsubjectswere 7
7
etal.(24) 98 menand hepatitisorcirrhosis drinking interferontherapy, anti-HCV-positiveand 9
3w8omen) pJiokseiitiUvenifvoerrasinttyi-HHoCsVpitaatl No 1.00 hirirsetgoulolagricresgtaegnienrga,tion HheBavsAygd-rninegkaintigvew.aHsadbeifitunaeld Jpn 77 by
Yes 3.04(1.31– asanaveragedaily J g
C u
7.09) ceothnasnuomlpfotiron.o5fy6e5args.of lin est o
O n
Morietal. 1992– 3052(974 ResidentsinatowninSaga Incidence 22(14men Historyofhabitualalcoholconsumption Sex,age Anti-HCVandHBsAg n 0
c 8
(25) 97 m2w0oe7mn8eann)d prefecture awnodm8en) NYeos 1202 11..0207(0.46– satdajtuusstewdafsoar.vailablebutnot ol200 April 2
3.47) 8;3 019
Neverdrinker 10 1.00 0.87 One‘drink’correspondstoa 8
(
1–19 3 2.05(0.48– glassofsake. 12)
drink-years 8.79)
9
8
2
Continued 1
Table1. Continued
8
2
2
Reference Study Studypopulation Category Number Relativerisk Pfor Confoundingvariables Comments
period among (95%CI trend considered
cases orP)
Numberof Sourceofsubjects Event Numberof A
subjects followed incidentcases lc
o
for ordeaths h
o D
analysis l o
d w
r n
(cid:4)20 1.14(0.40– in lo
drink-years 3.26) kin ade
N(He2tao6amd)la.a(de2at7a)l. 19129290780200–– 34m06e69nm(a2ne2dn7 AcdiPcnioialtasmtcytgiio,etnphnuOoeottnsssiloeasiwcnadkstaieat,ihdtnwaccThlhpioarnskoyihanccataihsdcluilaybktieriecn DInecaidthence N52otdescribed hccAOaoel/rpncEiasonutrhooamomctilepoaltlifuoolnrar 14..67)(0.3– ApAlggateee,,lsceeatsrl,uenimndtaebrriflyiereruoabrnin, AanAnolntlttii-st-HeuHsbCtCejVedVc.-tpsaonwsdietiHrveBesaAndgwere gandliverca d from https://ac
n a
242 hepatitisCduetoblood therapy,durationfrom HBsAg-negative.Excessive c d
Notexcessive 1.00 e e
women) transfusionatNational infection,fibrosis alcoholconsumptionwas r m
NagasakiMedicalCenter Excessive 23..2581)(1.00– dcoefinsnuemdpatsioannoaflc.oh5o0lg/day risk ic.ou
p
for5years. .c
o
Takimoto 1989–? 356 Patientswithhistologically Incidence Notdescribed Alcohol Age,sex,blood Allsubjectswere m
etal.(28) provenchronichepatitisC drinking transfusion,viralload, anti-HCV-positiveand /jjc
o
aHtoNspiiigtaaltaanUdnoivneershitoyspitalin No 1.00 vfiibrraolssius,bAtyLpTe,,sptlaagteeleotfs, HdrBinskAingg-nwegaastidveefi.nAeldcoahsol /artic
Niigata,whodidnot Yes 4.30 interferondose havingconsumed.80g le
respondtointerferon (P¼0.048) ethanoldailyfor.5years. -ab
therapy s
tra
Ueteatal.k(e29) 12908080– 91men HPaBtiseAntgs-nweigthative Incidence 13men aClucmohuollatiinvteake Anti-HBc HABllspAagti-ennetgsawtievree, ct/38
anti-HCV-negative (kg) anti-HCV-negative,and /1
2
UalncoivheorlsiictyciHrrohsopsiitsalatJikei 1in2c0r0eaksge 73.17.5()1.9– 0.0047 a(inalcnteodrhv9oa5lli)%c.wTcaohsnenfiohdtaezdnaecrsedcrriabteiod /816/8
7
intheoriginalpaper,and 7
9
wasestimatedbyoneofthe 7
7
authors(KT). b
y
Iwasaki 1986– 792(533 HepatitisCpatientswithor Incidence 23(20men Alcohol Fibrosisstaging,age Allsubjectswere gu
etal.(30) 2003 menand withoutChildAcirrhosisat and3 consumption anti-HCV-positiveand es
2w5o9men) OHkoaspyiatmalaaUndnipvaerrtsiictiypating women) ,50g/day 1.00 HBsAg-negative. t on 0
irnesstpiotuntsieontso,iwntiethrfesurosntained (cid:4)50g/day 39..8464)(1.58– 8 Ap
Ogimoto 1988– 66974 Residentsin45areas Death 184(number Male,40–59 (n¼16715) Collaboratinginstitute HBsAgandanti-HCVwere ril 2
0
etal.(31) 99 (28343 throughoutJapan bysexand years nottested. 1
9
menand agenot
Neverdrinker 1.00
38631 described)
women) Ex-drinker 8.11(3.17–
20.77)
Currentdrinker 0.65(0.27–
1.52)
Male,60–79 (n¼11628)
years
Neverdrinker 1.00
Ex-drinker 3.48(1.86–
6.54)
Currentdrinker 0.75(0.43– D
1.31) o
w
n
Female,40–59 (n¼22528) lo
a
years d
e
d
Neverdrinker 1.00 fro
Ex-drinker 3.85(0.48– m
30.93) http
Currentdrinker 01..2830)(0.03– s://a
c
a
Female,60–79 (n¼16103) de
years m
ic
Neverdrinker 1.00 .ou
p
Ex-drinker 4.18(1.47– .c
o
11.88) m
Currentdrinker 0.59(0.25– /jjco
1.43) /a
rtic
Nakaya 1990– 21201 Residentsin14 Incidence 48men Neverdrinker 3 1.0 0.21 Age,smoking, HBsAgandanti-HCVwere le
etal.(32) 97 men municipalitiesofMiyagi education,daily nottested. -a
Ex-drinker 10 6.6(1.8– b
prefecture consumptionoforange s
24.2) andotherfruitjuice, tra
c
Currentdrinker 35 2.7(0.8– spinach,carrotor t/3
8.9) pumpkin,andtomato 8
/1
2
,22.8g 11 2.8(0.8– /8
alcohol/day 10.1) 16
/8
(cid:4)22.8g 24 2.7(0.8– 7
7
alcohol/day 8.9) 9
Ikedaetal. 1995– 846(473 Patientswith Incidence 237(151men Patientswith (n¼576) Sex,age,smoking, Allsubjectswere Jpn 77 b
y
(33) 2005 menand HCV-associatedchronic and86 chronic alcoholconsumption, anti-HCV-positiveand J g
373 hepatitisorcirrhosisat women) hepatitis responsetointerferon HBsAg-negative. C ue
women) Kanydot1o4UafnfiivlieartseidtycHoroespital None 57 1.00 therapy,anti-HBc linO st on
hospitals (reference) n 0
c 8
,30g/day 14 0.75(0.39– o A
l p
1.44) 200 ril 2
(cid:4)30g/day 23 10..1625)(0.37– 8;3 019
8
Patientswith (n¼270) (1
2
cirrhosis )
None 99
Continued 8
2
3
824 Alcohol drinking andlivercancer risk
similar classification was possible based on the type of
s
nd epatiti c4o6n,4tr8o,4ls9:,5h1o–s5p6it,a5l8)or(nc¼om1m8)unvitsy. cpoantiternotlss (w3i5th,37C,4L0D–
a h
wereositiveative. odyto (in3c9l,4u7d,e5d0,h5o6s,5p7it)aolrcoHnBtrVolcsaarrsiewrsel(l3)6()T(anb¼le62;).onIne sstiuxdcya(s5e6–)
NumberRelativeriskPforConfoundingvariablesCommentsamong(95%CItrendconsideredcasesorP) 1.00(reference)110.42(0.22–0.83) 331.03(0.65–0.83) Age,sex,diabetes,bodyAllsubjectsmassindex,serumanti-HCV-palbumin,bilirubin,ALT,HBsAg-neg1.00prothrombintime,platelets,1.41(1.07–alpha-fetoprotein1.86) Bc,antibodytohepatitisBcoreantigen;HCV,hepatitisCvirus;anti-HBs,antibatio,ratioofobservedtoexpectednumber;HCV-RNA,hepatitisCvirusRNA. ciar(brwrtad(crAsa(pniee1ei2uopttonaeeosemmetps31thbtatnAAdoknaipwe,o,orjetao1kl2miceertarwanrieesncn6iot3ctnctcnutcepaoeaev,aglstct,is2dnmusodnsid2nsesotsvt1welstuggr4utfimaahhem,ismud–w,i2nltrvelaiee2taciidwlyg3octhoeilevey7roiglo.,hsssdoyaeree2,hC(h–tee2neAsraes1lt4otaovrL4yas3t,ckr5w,mlrsfesoar2i0fDibo,stgcirntoedn1c7tu,onoolreaeh3rilr7pdh–snctestalcfie4,fhhispoioeoniotg32oneo)atcoiowsmkt–r0u2hsgoHltoiwimasil,i)occ,dotenannoo3ilCmietoudiegtrlrstvghwn1ediretnpVr;t,noevro2s,spt-aea3issstelr2usotofi(entthtl3auouuleii2upfrdanvya)clasecd(tdc6dnhe1sedsnoesstdhlh,isdsh8tfst3tiheepuceoouoHvosh,e4(osmi2sauod)rcdcefo1nB)trl0sririiiiro1w(t3taveariae(no,h(V4nt4ecs2,s1etTtssnniy16siinas5vtr5woigaoo,t4uionstfe)ds4r,nbncnieoh,d1cfuaep7odn1fliasslteiib7naeeo,bprel6sc,ea5rjti,tsocsassdaTh,se,i2sni0ioet1wonfitcs1tt2aki,iwrwicn9im5hdootee-vbde,vsiad,6r3uncnehaer,leef3oetn,iesat3pso–tdenwt2eisasdakshs)ror5tt(wt)nts.eoelis(1niw8rt3tsyfioo1a3tehoos9)oIuo)rrise4n.ren.n.ea,techbded3m,hsagsvpiO1esci1,asnteeseoo9oeaCpowtaf,dnoarsiilrd3h,ockvoL3gtiltemteo2ihsneeeheno2hra4Drri)dndydeeeesf--)-tt,. Downloaded from https://academic.oup.com/jjco/artic
Category ,30g/day 30g/day(cid:4) Alcoholconsumption 80g/day(cid:3) .80g/day Cvirus;anti-Hnsferase;O/Er t5((i3T1v8a,e5,b4a4l1es–s,s4o552c6,i,5a5at38nio))d,nas4nm)dw.oeaFdroeewrrfeaotathuekenpdproeoisnmsiita1tiivi4vneed(3ae5sras,,s3osn6coo,ic4ai0taai,sot4sin2oonc–insi4a4toii,no4nen7,f(4wo39u7a–s)r le-abstract/38
Table1.Continued ReferenceStudyStudypopulationperiod NumberofSourceofsubjectsEventNumberofsubjectsfollowedincidentcasesforordeathsanalysis Ohkietal.1994–1431(727PatientswithpositiveIncidence340(34)2006menandHCV-RNAatTokyo704UniversityHospitalwomen) CI,confidenceinterval;HBsAg,hepatitisBsurfaceantigen;anti-HCV,antibodytohepatitisBsurfaceantige;LC,livercirrhosis;AST,aspartateaminotransferase;ALT,alanineaminotra rte4acrrasmttpemtptwmpaoieiiiietxomsllao5aoeovouhpccaoapstntpOFt,rcnennidiytooopisoe4ostceloiietivrrhhnloac9wrrhnlnecaantoot(tseyitioone,tefso1sseaintlayt5rmsdfllias,nssdn8tahiood1saloi(ntdaafldi,etnraewor,rhnl2poucygcdm5eaerrtw,neai0udiiothpel3fattbsnothorde)niodnbeohahhptt,–eekonaoudipifrabayoscsoowc5ioktsgnrmtasdoenusuotprn6ueutseu(hihduicgliCoinuns3n,ltstateeehtte5iio,oiridsb9diaLrnvrasvnen8utlnij,alepiy6eoeyDne4vgen)mvsasosoeo,0ndc6imgstitsaedsctnrdft%errc,hopiss4vuoooouelbitefiecacssiir8eannrosnsmmyditvvooer(lr,tfaivtughoe5e5sevlimceoeratoosenyromof72rieinlunwanrroaflmltl))pr(teoscsyieihocsst.naist3cvosaeiwhctutanhe,lIooho6rnesatwnnanspreiaitcnvifr,dlaeftnlocihac4ttciiroitststaiegCtathednaearhh7ocyvsihlsdtatrr.feioelLy,ohiereomosslo5oocneaShcodrDeenn1auwo0snaitoliioilvanasitc8ussnnsna,fdc)-rse5spfoko(.abtcdtteutleecseri6rahnrHh,iejer.oipocaore.etas)aotasgtlaiCstnpCclyc.ttyeneltsisel.hoesoistuoVntnto,atcse–ourchndiuditthtot1rn(wfotsmchoioleideo1n5voaieonotudrolesoir5psceosniisnesgaftH(rvusr,kainustes3k1hssedrmssiioHiBnneto5r7ntrdireowbloeuxaplpVB,i,agaein3dn2ndedlktosssintVrlic7it2ktsiitseiesostwhuneanCpoo,l,lsiiaen43yidoscsltffifoccuesLavei.e0oea3iuiisoeecvoseetsaacDrIri)––tdonnheessfr---f---,, /12/816/877977 by guest on 08 April 2019
Table2. Case–controlstudiesonalcoholdrinkingandlivercanceramongJapanese
Reference Study Studysubjects Category Relative Pfor Confoundingvariables Comments
period risk(95% trend considered
CIorP)
Typeandsource Definition Number Numberof
ofcases controls
D
Inabaetal. 1977– Hospital-based Cases:58%were 62(49 62(49men Notdaily 1.0 Matched(1:1)forsex,age, HBsAgwastestedbutnot o
w
(35) 79 (7hospitalsin histologicallyconfirmed; menand and13 andhospitalAdjustedfor adjustedfor.Anti-HCVwas n
Yamanashi) Cheopnattrioclsd:ispeaatiseentswithout 1w3omen) women) Daily (3P.2,0.05) matchingfactors nottested. loade
d
Oshima 1972– Nestedcase–control Cases:confirmedby 20men 40men Noneor,1go/day 1.0 ,0.05 Matched(1:2)forbirthyear Allsubjectswere fro
etal.(36) 80 (HBsAg-positive recordlinkagewiththe Adjustedforsmoking HBsAg-positive.Anti-HCV m
blooddonorsat OsakaCancerRegistry; 1–,3go/day 5.4 wasnottested. h
OsakaRedCross Controls:healthyHBV (cid:4)3go/day 8.0 ttps
BloodCenter) carriers ://a
c
Hiragaetal. 1981– Hospital-based(one Cases:50%werehistolo- 78men 78men Notdaily 1.0 Matched(1:1)forageand HBsAgwastestedbutnot a
d
(37) 85 universityhospital) gicallyconfirmedasHCC; residentialareaAdjusted adjustedfor.Anti-HCVwas e
Daily 1.7(0.8– m
Controls:inpatientsor 4.0) formatchingfactors nottested. ic
outpatientswithvarious .o
u
diseases p
.c
Kiyosawa 1980– Nestedcase–control Cases:confirmedby 36men 67men Forprimarylivercancer Nomatching HBsAgwastestedbutnot om
etal.(38) 87 (militarymenwho autopsyand/or adjustedfor. /jjc
hadundergone serologicalandimaging o
athnogriootgraraspthbyetwweitehn eCxoanmtrionlast:ionnosl;ivertumor (cid:4),8800gg//ddaayy 11..201 Noadjustment TAhneti-rHelCatVivewraissknowtatsesntoetd. /artic
1943and1946) bybiochemicaland (0.54– describedintheoriginal le-a
serologicaltestsand 2.74) paper,andwasestimatedby b
s
imagingexaminations oneoftheauthors(KT). tra
c
ForHCC t/3
8
(cid:4)80g/day 1.0 /1
2
/8
,80g/day 2.91 1
6
(0.95– /8
8.92) 77
9
Ketoabla.y(a3s9h)i 189875– H(Koasnpaitzaalw-baased CwaitshesH:CciCrrhaottaicutpoaptsiye;nts 4m8en(4a0nd 4an0d(2173men Ayelacrosh)olintake((cid:4)75g/day,(cid:4)10 Nomatching HadBjussAtegdwfoasr.testedbutnot Jpn 77 b
y
UniversityHospital) Controls:cirrhotic 8 women) J g
patientswithoutHCCat women) No 1.0 Noadjustment Anti-HCVwasnottested. C ue
autopsy Yes 1.4(0.6– Therelativeriskwasnot lin st o
3.4) describedintheoriginal O n
paper,andwasestimatedby nc 08
oneoftheauthors(KT). ol Ap
Tsukuma 1983– Hospital-based Cases:histologically 229(192 266(192 Notheavy 1.0 Frequency-matchedforsex Anti-HCVwasnottested. 200 ril 2
etal.(40) 87 (DCiesenatesresf,oOrAsadkual)t cCoonnfitrromlse:dinapsaHtiCenCts;with m37enand m74enwoanmden) Heavy 3.2(2.0– aangde,aHgBesAAdgj,ushtiesdtofroyrosfex, Hasedavriynkdirningk3in‘ggow’assodfesfiankeed 8;3 019
5.1) 8
gastrointestinaldisease, women) bloodtransfusion,smoking, perdayfor.10years. (
1
orexamineesforhealth 0–9999‘go’s 1.0 0.03 andfamilyhistoryofliver 2
)
checkupsor cancer
10000–39999‘go’s 1.0(0.6–
gastroendoscopy;noliver
1.6)
8
Continued 2
5