農(nóng)村現(xiàn)場(chǎng)肝癌早篩早診隊(duì)列建設(shè)與應(yīng)用課件

啟東農(nóng)村現(xiàn)場(chǎng)肝癌早篩早診隊(duì)列建設(shè)與應(yīng)用啟東農(nóng)村現(xiàn)場(chǎng)肝癌早篩早診隊(duì)列建設(shè)與應(yīng)用I.

背 景2I.背 景2QDLCI

CHEN

JG6第一批上海市派遣赴啟東縣腫瘤科研小分隊(duì)1971年11月隊(duì)長(zhǎng)為上海市腫瘤醫(yī)院原副院長(zhǎng)俞魯誼，指導(dǎo)員為上海市腫瘤醫(yī)院的許維珍。隊(duì)員合計(jì)13人，來(lái)自上海市腫瘤醫(yī)院、上海中山醫(yī)院、上海市腫瘤研究所、上海第一醫(yī)學(xué)院等內(nèi)外科、婦科、護(hù)理、檢驗(yàn)及衛(wèi)生統(tǒng)計(jì)專業(yè)。X 5

年QDLCICHENJG6第一批上海市派遣赴啟東縣腫瘤科研隊(duì)長(zhǎng)為江蘇省人民醫(yī)院副院長(zhǎng)(當(dāng)時(shí)稱副主任)薛集安，指導(dǎo)員是江蘇新醫(yī)學(xué)院（現(xiàn)南京醫(yī)科大學(xué)及南京中醫(yī)藥大學(xué)）的尹力。隊(duì)員合計(jì)30人，來(lái)自省人民醫(yī)院、省中醫(yī)研究所、南京大學(xué)、南通醫(yī)學(xué)院（現(xiàn)南通大學(xué)）及附院、省地理研究所、中科院南京土壤研究所、江蘇新醫(yī)學(xué)院、江蘇農(nóng)學(xué)院（現(xiàn)揚(yáng)州大學(xué)）、省農(nóng)藥研究所（揚(yáng)州）、省地質(zhì)水文大隊(duì)等單位。QDLCI

CHEN

JG 7第一批江蘇省啟東科研醫(yī)療隊(duì)1972年10月X 5

年隊(duì)長(zhǎng)為江蘇省人民醫(yī)院副院長(zhǎng)(當(dāng)時(shí)稱副主任)薛集安，指導(dǎo)員是QDLCI

CHEN

JG 8ShanghaiMortality

from

Liver

Cancer

by

Township:

Jiangsu

Province<

1

per

105/yr>

50

per

105/yr25-fold

change

in

HCC

rate

in

200

kmMedian

age

of

liver

cancer

death

is

45-50

yearsQidongQDLCICHENJG 8ShanghaiMortalChen

JG,

QDLCI9ChenJG,Zhang

SW.

Seminar

Cancer

Biol.

2011;

21(1):

59-69.

ChenJG,QDLCI9ChenJG,Zhang0Factors

AttributedtoLiver

Cancer? Hepatitis

B

Virus? AflatoxinB1Chen

JG,QDLCI 1主要病因Kensler

TW,

et

al.

NatureRev

Cancer,

2003主要危險(xiǎn)因素乙肝病毒黃曲霉毒素0FactorsAttributedtoLiverCaCrude

Rate,

ASR,

Truncated

Rate

and

Cummurative

Ratefor

Incidenceof

Leading

Cancer

Sitesin

Qidong,

1972-2011部位SiteICD-10位次Rank例數(shù)No.CasesCR

(1/105)CASR(1/105)WASR(1/105)%截縮率Trunc.Rate35-64

(1/105)累積率Cum.Rate0-64 0-74(%) (%)累積危險(xiǎn)Cum.

Risk

0-74(%)肝

LiverC2212839863.1739.3250.7130.61119.064.005.285.15胃

StomachC1621540134.2616.2525.5916.6040.031.413.153.10肺

LungC33-3431534034.1215.7425.4116.5336.961.323.273.22結(jié)直腸ColonrectumC18-214603513.436.209.806.5014.360.511.161.15食管EsophagusC15544149.824.187.084.769.030.320.880.88乳腺BreastC50634527.684.656.133.7215.310.490.640.64胰腺

PancreasC25732797.293.295.363.537.440.260.670.66白血病LeukemiaC91-95819304.293.473.922.084.810.250.360.36腦（CNS)BrainC70-72917853.972.673.341.921.920.230.360.36膀胱

BladderC671016193.601.522.551.743.300.120.290.29NHLC82-85/961114723.271.962.651.594.270.170.300.30宮頸C531212112.691.502.101.314.390.150.230.23鼻咽C11138291.841.101.470.893.130.110.160.16多發(fā)性骨髓瘤C90147151.590.841.240.771.960.070.160.16皮膚其它C44157011.560.611.060.761.120.040.100.10骨C40-41165941.320.821.080.641.570.070.120.12前列腺C61175311.180.390.760.570.350.010.080.08膽囊膽管C23-24185301.180.540.850.571.310.040.100.10卵巢C56194721.050.650.860.511.890.070.090.09小腸C17204100.910.420.660.440.920.030.070.07全部All

92780206.39110.80159.11100.00288.4410.1018.1916.63發(fā)病水平CrudeRate,ASR,TruncatedRat粗發(fā)病率標(biāo)化發(fā)病率CASR

of

leading

cancer

sites,

Qidong110100Incidenceper

100

000Crude

Incidence

of

leading

cancer

sitesLiverStomachLungColon-rectumEsophagusBreastPancreas1972

1977

1982

1987

1992

1997

2002

2007

2012YearLeukemia1101001972

1977

1982

1987

1992

1997

2002

2007

2012YearASR

China

per

100

000LiverStomachLungColon-rectumEsophagusBreastPancreas

Leukemia粗發(fā)病率標(biāo)化發(fā)病率110100Incidenceper10II. 早診早治13II. 早診早治13QDLCI

CHEN

JG14第1階段：1970’s采用甲胎蛋白（AFP）檢測(cè)方法，在啟東自然人群中檢測(cè)

AFP

200多萬(wàn)人次，其中普查近180萬(wàn)人次，檢出肝癌1000多例，其中早期(Ｉ期)病例達(dá)到35%。這個(gè)階段解決了肝癌早期診斷的問(wèn)題，

證實(shí)AFP

應(yīng)用于現(xiàn)場(chǎng)的普查，其簡(jiǎn)便、易行、敏感、特異。啟東肝癌篩查工作的歷程QDLCICHENJG14第1階段：1970’s感、特異QDLCI

CHEN

JG15第2階段：1980’s啟東重新估價(jià)了AFP

普查的作用，認(rèn)為

AFP

普查的關(guān)鍵取決于普查對(duì)象、范圍的擇優(yōu)選擇；因此提出了選擇特定的高危人群進(jìn)行肝癌篩檢的概念。在這個(gè)階段，明確提出乙型肝炎表面抗原（HBsAg）陽(yáng)性的30~59歲的男性為啟東肝癌的高危險(xiǎn)人群。啟東肝癌篩查工作的歷程QDLCICHENJG15第2階段：1980’s高危險(xiǎn)人6QDLCI

CHEN

JG 1高風(fēng)險(xiǎn)人群FemaleMale30600（+）（-）General

populationHBsAgMale30-59Yrs

HBsAg

(+)High

risk

pop.Sex

性別Age

年齡乙型肝炎表面抗原6QDLCICHENJG 1高風(fēng)險(xiǎn)人群FemaleMa第3階段：1990’s選定啟東40萬(wàn)人群范圍中的肝癌高危險(xiǎn)人群進(jìn)行了周期性的篩查實(shí)踐，確立了肝癌高危險(xiǎn)人群篩檢模式和可行方案。于“八五”期間對(duì)肝癌高危險(xiǎn)人群模式、現(xiàn)場(chǎng)實(shí)施方案以及周期性篩檢的亞臨床平均滯溜時(shí)間、靈敏度和預(yù)測(cè)值及普查的超前時(shí)及最佳篩檢間隔等進(jìn)行了評(píng)價(jià)分析

。QDLCI

CHEN

JG 17啟東肝癌篩查工作的歷程第3階段：1990’s啟東肝癌篩查工作的歷程QDLCI

CHEN

JG 18第4階段：2005~衛(wèi)生部疾病控制局和中國(guó)癌癥基金會(huì)根據(jù)《中國(guó)癌癥預(yù)防與控制規(guī)劃綱要》（2004-2010年）的部署，會(huì)同部分省衛(wèi)生廳共同建立了癌癥早診早治示范基地，啟動(dòng)了癌癥早診早治項(xiàng)目。江蘇啟東與廣西扶綏作為全國(guó)肝癌早診早治示范基地，自2007年開(kāi)展了以肝癌的早診早治篩查工作。啟東肝癌篩查工作的歷程QDLCICHENJG 18第4階段：2005~啟東肝“肝癌早診早治示范基地”掛牌儀式建立市癌癥早診早治領(lǐng)導(dǎo)小組“肝癌早診早治示范基地”掛牌儀式超

前

時(shí)計(jì)算出高年齡段

(44~59

歲)

與低年齡段(30~44歲)的平均滯留時(shí)間(MST)值分別為0.47年和

0.55

年，總的超前時(shí)為

0.49

年。用AFP和Ｂ超作為篩查手段，篩查相對(duì)于未篩查的死亡危險(xiǎn)度顯著下降（

OR

＝0.631），篩查可以降低肝癌死亡的危險(xiǎn)。超前時(shí)計(jì)算出高年齡段(44~59歲)與低年齡段篩

檢

間

隔用Logistic

模型分析連續(xù)陰性篩查次數(shù)及最后一次陰性篩查至病例診斷的持續(xù)時(shí)間(TSLT)：陰性篩查對(duì)肝癌死亡的保護(hù)效應(yīng)隨時(shí)間的推移而逐步下降,

至陰性篩檢后1.5年左右消失，說(shuō)明兩次篩查的間隔不能超過(guò)一年半。

AFP一次陰性篩查后，OR下降至基準(zhǔn)的10~20%左右;

連續(xù)２次陰性篩查后,

OR值下降至基準(zhǔn)的1~2%。因此,

連續(xù)2次陰性篩查后可適當(dāng)延長(zhǎng)下次篩檢時(shí)間。篩檢間隔用Logistic模型分析連續(xù)陰性篩查次數(shù)及可檢測(cè)的臨床前期（DPP）經(jīng)對(duì)前瞻資料統(tǒng)計(jì)進(jìn)行再抽樣組成病例對(duì)照,對(duì)最后一次陰性篩查至肝癌死亡的持續(xù)時(shí)間的分析來(lái)確定DPP。結(jié)果當(dāng)DPP為

14

個(gè)月時(shí),

最大對(duì)數(shù)擬然值達(dá)極大,

因此用ＡFP篩查肝癌的DPP為14

個(gè)月,

即應(yīng)在病例診斷前一年半內(nèi)進(jìn)行篩檢,

效益最佳；也說(shuō)明篩查可以提前診斷肝癌?？蓹z測(cè)的臨床前期（DPP）經(jīng)對(duì)前瞻資料統(tǒng)計(jì)進(jìn)行再抽樣組成病例Survival

of

liver

cancer

cases

in

screened

(n

=

240)

and

control

(n

=

108)

groups

(2

month

prevalent

cases

excluded)0.00.20.40.60.81.001224364860MONTHSCTRLSCREENEDSurvival

probabilitySurvivaloflivercancercases2424QDLCI

CHEN

JG25國(guó)家衛(wèi)計(jì)委

癌癥基金會(huì)

QDLCICHENJG25國(guó)家衛(wèi)計(jì)委Early

Diagnosis

and

Treatment

for

the

Liver

CancerCases

Screened

from

a

Recent

ProgramQidongYearPerson

TimesScreenedNo.

Cases

*DetectionRatein

Group

AGroup

AGroup

B%No.%No.%20071

6161511.861173.331280.0020082

5762531.941664.001976.0020093

5673261.792784.383093.7520103

63827111.482592.592592.5920114

48120140.891575.001995.0020124

46520120.901785.001785.0020134

22519130.901578.951789.4720144

3611170.50763.6411100.0020154

27017150.801694.1217100.00合計(jì)33

199186821.1214980.1116789.78Early

Diag.Casesin

Group

AEarly

Treatment

Casesin

Group

A*Group

A:

Detectedbyscreening;

Group

B:

Found

between

the

screening

points.26EarlyDiagnosisandTreatmentIII.

隊(duì)列應(yīng)用27III.隊(duì)列應(yīng)用27281.

前瞻研究隊(duì)列在篩查的基礎(chǔ)上，開(kāi)展肝癌的前瞻研究281. 前瞻研究隊(duì)列在篩查的基礎(chǔ)上，開(kāi)展肝癌的前瞻研究2929HBsAg

Cohort

and

Person

Years

Followed

up

(1977-2007)AgeHBsAg

CarrierHBsAg

Non-carrier

All .MFM+FMFM+FMFM+F15-338.0562.0900.01557.02782.04339.01895.03344.05239.020-920.01363.02283.04375.97259.611635.55295.98622.613918.525-1458.22222.43680.67044.211980.319024.58502.414202.722705.130-1817.32982.24799.58986.815460.624447.410804.118442.829246.935-2118.43472.45590.810488.418306.228794.612606.821778.634385.440-2365.03943.66308.612206.321387.033593.314571.325330.739902.045-2251.33897.36148.613019.122661.835680.915270.426559.141829.550-1785.63232.25017.811742.420650.632393.013528.023882.737410.755-1398.32580.23978.510273.317816.028089.311671.620396.232067.860-1137.21896.03033.29109.915363.524473.410247.117259.527506.665-857.61474.52332.18080.013342.321422.38937.614816.823754.470+1389.52387.83777.316535.727026.143561.817925.229413.947339.1合計(jì)17836.430013.647850.0113419.0194036.0307455.0131255.4224049.6355305.0HBsAgCohortandPersonYearsHBsAgCarrierStateandLiverCancer

by

Period,Qidong,ChinaHBsAg

(+)HBsAg

(-)PeriodSexP-YrsNo.RateP-YrsNo.RateRR95%

CIM1103041371.71476541633.5811.076.08-21.131977-1986F1279718140.6666598812.0111.714.84-31.12T2382759247.621142522421.0111.797.22-19.81M13402.283619.3075428.83951.7011.988.09-18.001977-1998F21653.542193.96131982.71511.3717.069.27-33.13T35055.7125356.58207411.55426.0413.699.88-19.21M17836.4118661.57113419.06153.7812.308.96-17.041977-2007F30013.655183.25194036.03417.5210.466.70-16.54T47850.0173361.55307455.09530.9011.709.06-15.19HBsAgCarrierStateandLiver32Age

Specific

Rates

ofLiverCancerin

HBsAg

CarriersandNon-Carriers110100100010000年齡)萬(wàn)

01/

1

(率病發(fā)HBsAg(+)

男HBsAg(+)

女HBsAg(-)

男HBsAg(-)

女M

37.76F 10.46M 3.07F 1.00HBVChen

JG,

etal.

ChinJEpidemiol,

2010,

31(7):

721-726.25- 30- 35- 40- 45- 50- 55- 60- 65- 70+AgeIncidenceper

10000032AgeSpecificRatesofLiver332.

免疫預(yù)防隊(duì)列建立新生兒出生免疫隊(duì)列開(kāi)展隨訪研究332.免疫預(yù)防隊(duì)列建立新生兒出生免疫隊(duì)列開(kāi)展隨訪研究34693047075639520658637376563772535756761458146531518902000400060008000100001400012000Vaccinees

&

Controls

per

Year

.19181984

1985

1986

1987

1988

1989

1990YearsControl40,828Vaccinated40,605HB

Vaccination

Study,1984-1990,

QidongImmunization34693047075639520658637376563735Aimed

to

observe

the

final

result

of

incidencerate

ofliver

cancer

by

HBV

vaccinationin

children35Aimedtoobservethefinalr36Cumulativemortalityprobabilityofliverdiseases

in

the

vaccination

andcontrol

groups.36Cumulativemortalityprobabi373.

基因突變研究利用篩查隊(duì)列開(kāi)展嵌式病例對(duì)照研究373. 基因突變研究利用篩查隊(duì)列開(kāi)展嵌式病例對(duì)照研究38Screening

(A)

and

control

(B)

cohortsA

2554Year(1989)199019911992199319941995X

=

ScreeningXB

1346

XX XX

+1158

XX XXX3712X

+5231869Blood

sampleswere

collected

and

storedStudy

design: size

andthe

times

of

screening

examinations

(X)36,000+

men screened5581

HBsAg(+)Subjects38Screening(A)andcontrol(BQidong

Liver

Cancer

Cohort

(1989-2003)667 Cases

of

Liver

Cancer

fromthe

cohort536 Samples

with

sufficient

serum

volume

(>

100

μl)515 Cases

deceased

prior

to

12-31-2003355 (69%)

DNA

recovered

from

serum

295 (83%)

Mutation

at

1762T/1764A83%

of

analyzable

serum

samples

contained

double

mutation

HBV

DNAChenJG,etal.AccelerationtodeathfromlivercancerinpeoplewithhepatitisBviral

mutations

detected

in

plasma

bymass

spectrometry.

CEBP,

2007,

16(6):1213-1218.QidongLiverCancerCohort(1940657685708088748390788692828893P

=

0.012P

=

0.083P

=

0.068ENHANCEDRISK

OF

LIVER

CANCER

FROMHBV

DOUBLE

MUTATION

(%

POSITIVE)Mutations

are

more

common

in

younger

peopleDiamond

Graphmodeling

fromLi

&

Mu?oz,

Am

Statistician

(2003)Ahigherprevalence

of

HBV

mutations

was

observed

in

thosewhohadshorter

survival

times

after

thedeterminationof

mutationChen

JG,

etal.

CEBP,

200540657685708088748390788692828841Box-percentile

plots

showing

the

distribution

ofnumber

ofthe

cyclesneeded

to

detect

HBV

1762T/1764A

mutation

by

HCC

case/controls

statusChenJG,

QDLCI

among

278

cases

and

250

controls

with

mutation

31病例對(duì)照?qǐng)D示病例組的HBV突變水平在50%百分位時(shí)是對(duì)照組的16倍Mu?oz

A,

Chen

JG,

Egner

PA,et

al.Carcinogenesis.

2011,

32(6):

860-865OR

=

6.72The

level

of

the

HBV

mutationwas

15-fold

greater

at

50th

percentile

in

cases

than

in

controls

(P

<

0.001). or,

the

OR

was

6.72,

i.e.,

the

mutation

in

the

cases

was

6.72

times

larger

than that

ofthe

controls.41Box-percentileplotsshowing424.

遺傳資源隊(duì)列結(jié)合多項(xiàng)重大項(xiàng)目開(kāi)展資源收集及樣本庫(kù)建設(shè)424. 遺傳資源隊(duì)列結(jié)合多項(xiàng)重大項(xiàng)目開(kāi)展資源收集及樣本庫(kù)建肝癌相關(guān)樣本庫(kù)建設(shè)維護(hù)及基線水平調(diào)查流行病學(xué)背景資料的建立與隨訪肝癌病例對(duì)照研究及其分子流行病學(xué)研究雙生子及其肝癌生物資源的采集與保存特殊隊(duì)列資料的收集、保存完成高危人群、核心家系成員的血樣、尿液的建庫(kù)863計(jì)劃重大疾病相關(guān)基因研究項(xiàng)目遺傳資源的調(diào)查和采集課題 Z19-01-01-01肝癌樣本的調(diào)查與采集啟東肝癌高發(fā)區(qū)雙生子及肝癌遺傳資源的收集與保存十二五國(guó)家科技重大專項(xiàng) 46791282

-0-2012ZX10002009/

018高發(fā)現(xiàn)場(chǎng)特殊病例隊(duì)列資源的收集、保存和應(yīng)用病毒性肝炎相關(guān)肝癌樣本保藏及相關(guān)數(shù)據(jù)庫(kù)共享技術(shù)平臺(tái)

2012ZX10002010

-001003

肝癌相關(guān)樣本庫(kù)建設(shè)維護(hù)及基線水平調(diào)查863計(jì)劃重大疾病相關(guān)基調(diào)查表調(diào)查表血樣及分裝保留血樣及分裝保留4646475.

化學(xué)預(yù)防隊(duì)列建立隊(duì)列開(kāi)展化學(xué)預(yù)防并利用生物樣本作評(píng)估475. 化學(xué)預(yù)防隊(duì)列建立隊(duì)列開(kāi)展化學(xué)預(yù)防并利用生物樣本作評(píng)Clinical

Chemoprevention

TrialsRCT

in

Qidong,

PRC奧替普拉 葉綠酸 萊菔硫烷Oltipraz:

increased

aflatoxin-mercapturic

acid

excretion

in

urine(Wang

et

al.,

JNCI,

1999) 234

eligible

participants

from

aninitialscreening

of

1006

residents.Chlorophyllin:

decreased

aflatoxin-DNA

adduct

excretion

in

urine(Egner

et

al.,

PNAS,

2001)

180

eligible

participants

from

aninitial

screening

of

511

residents.Sulforaphane:

decreased

aflatoxin-DNA

adduct

excretion

in

urine(Kensler

et

al,

CEBP,2005)

333

eligible

participants

from

aninitial

screening

of

700

residents.Sulforaphane:

decreased

aflatoxin-DNA

adduct

excretion

in

urine(Egner

et

al,

Cancer

Prev

Res

(Phila).

2011) 50

eligible

participants

from

aninitial

screening

of

180

residents.Sulforaphane:

decreased

aflatoxin-DNA

adduct

excretion

in

urine(Egner

et

al.,

Can

Pre

Res,

2014)

300

eligible

participants

from

aninitial

screening

of

1205

residents.To

evaluate

the

efficacy

of

chemoprevention.ClinicalChemopreventionTrialChen

JG,

QDLCI49Agent Dose

and

Schedule Size

(duration) Biomarker

Modulation ReferencesOltiprazPlacebo,

q.d.125

mg,

q.d.500

mg,

q.d.234(2

months)2.6-Fold

increase

inurinary

excretion

of

AFB-NACat1mo.(125mg)and51%decreaseinAFM1at1mo.

(500mg);6%decreaseinAFB-AA

at2

mo.

(500mg);

no

effect

on

urinary

mutagens

or

oxidativeDNA

damage

productsJacobson

et

al.,(1997);

Zhang

etal.,

(1997);

Kensleretal.,(1998);

Wang

etal,.1999);

Camoirano

et

al.,(2001);Glintborg

et

al,.ChlorophyllinPlacebo,

q.d.

X3100

mg,

q.d.

X3(4months) AFB-N7-GuaDNA

adductsat3mo. 2001)Broccoli

SproutPlacebo,

q.d.excretion9%

decrease

in

urinary

excretion

of

AFB- Kensler

etal.,

(2005)

N7-gua

DNA

adducts

at

10days;Cross-overwash-out

→

SFR

(150μmol)Run-in

→

SFR

→

wash-out→

GRR20-50%

increases

inurinary

excretion

ofmercapturicacid(NAC)conjugates

ofairpollutants:acrolein,ethyleneoxide,

crotonaldehyde,

benzeneBroccoli

Sprout

GRR

+

SFRBlendPlaceboGRR

(600

μmol)+

SFR

(40μmol)291(12

weeks)In

progress:

primary

endpoints

are

urinary

biomarkers

of

food-andair-

borne

toxins

and

pollutantsunpublishedGRR ●400

μmol

GRR1993 1997200(14

days)200310%

decreas2e

0in

0po9llutant

P2he0T112013

2014奧體B普roc拉coli

Sprout

葉●氯R酸un-in→GRR西50蘭花苗飲料Glucoraphanin

and

sul西fora蘭pha花ne

苗飲料E（gn凍er

e干tal.粉,

(20）11);OltipGrRaRz?

SFR

Chloro(p80h0

μymlloiln)

→

Su(2l4fdoayrsa)

phaneelimination

pharmaScoukinleftoicrs;aphanKeensler

et

al.,

(2012)代謝試驗(yàn) 效果試驗(yàn) 配方試驗(yàn)劑(20量06)

用法試驗(yàn)M1e8t0abolism

tria5l

5%

DecErefafsee

cint

uterinsatry

excFreotiromn

ouf

la

tesEt

gnMeruetltailp,.l(e2-0d0o0;se

trialsClinical

Chemoprevention

TrialsTo

enhance

the

body’s

detoxifying

system

to

help

prevent

cancerChenJG,QDLCI49Agent Doseand50More50MoreChen

JG,

QDLCI從歷史樣本庫(kù)中抽取不同年份的代表性人群的血清學(xué)標(biāo)本，開(kāi)展黃曲霉毒素DNA加合物的測(cè)定，評(píng)估不同年份代表人群中的黃曲霉毒素暴露水平。Chen

JG,

Egner

PA,

Ng

D,et

al.

ReducedAflatoxinExposurePresagesDeclineinLiverCancerMortality

in

an

Endemic

Region

of

China.Cancer

Prev

Res,2013,

6(10):

1038–1045.51ChenJG,QDLCI從歷史樣本庫(kù)中抽取不同年份的代Aflatoxin-Albumin

Adducts

(pg/mg

albumin)002040608010020406080100Percent

of

Samples

Non-Detectable1989 1995

1999

2003 2009

2012Aflatoxin

Exposures

Have

Dropped

Dramatically

over

the

Past

28

Years

(>40-fold)過(guò)去28年中，黃曲霉毒素的暴露已經(jīng)大大下降黃曲霉毒素白蛋白加合物檢不出樣本的百分比Aflatoxin-AlbuminAdducts(pg536.

早診早治隊(duì)列536. 早診早治隊(duì)列QDLCI

CHEN

JG 54High

Risk

PopulationFemaleMale3060Age0（+）（-）General

populationHBsAgSexMale30-59Yrs

HBsAg

(+)High

riskpop.性別年齡乙型肝炎表面抗原QDLCICHENJG 54HighRiskPop5515581

HBsAg+ve screendfrom

50

000+ residents5515581HBsAg+ve screend56.Survivalof

liver

cancer

cases

in

screened(A:

n

=

240)and

control

(B:

n

=

108)

groups0.00.20.40.60.81.001224364860MONTHSCTRLSCREENEDSurvival

probabilityStage

I: 6.0%Stage

I:

29.6%Group

B:

Group

A:(2

month

prevalent

cases

excluded)ChenJG,

Parkin

DM,

ChenQG,et

al.

J

MedScreen.2003,10(4):204-20956.0.00.20.40.60.81.0012243648Early

Diagnosis

and

Treatment

for

the

Liver

CancerCases

Screened

from

aRecent

ProgramQidongYearPerson

TimesScreenedNo.

Cases

*DetectionRatein

Group

AGroup

AGroup

B%No.%No.%200716161511.861173.331280.00200825762531.941664.001976.00200935673261.792784.383093.752010363827111.482592.592592.592011448120140.891575.001995.002012446520120.901785.001785.002013422519130.901578.951789.47201443611170.50763.6411100.002015427017150.801694.1217100.00合計(jì)33199186821.1214980.1116789.78Early

Diag.Casesin

Group

AEarly

Treatment

Casesin

Group

A*Group

A:

Detectedbyscreening;

Group

B:

Found

between

the

screening

points.57EarlyDiagnosisandTreatment反復(fù)篩查發(fā)現(xiàn)肝癌病例與自助就診發(fā)現(xiàn)病例生存率比較（2007-2015）58陳建國(guó),

等.

中華腫瘤雜志,

發(fā)表中反復(fù)篩查發(fā)現(xiàn)肝癌病例與自助就診發(fā)現(xiàn)病例生存率比較（2007-IV. 效果評(píng)價(jià)59IV. 效果評(píng)價(jià)59Analysis

of

HBV

Mutations

in

Plasma

Samples

of

LiverCancer

CasesPlasma

samples

of

adequate

volume

were

available

for

512

of

the

667

liver

cancer

cases.HBV

DNA

was

found

in

371

(72.5%)

of

512

samples.Using

mass

spectrometry,

mutations

in

HBVwere

determined

and

294(79.2%)

of

these

samples

contained

atwo

nucleotide

1762T/1764A

mutation.37

of

the

294

samples

had

an

additional

double

mutation

in

the

HBV

X-gene

coding

sequence.16

samples

had

novel

mutations

in

the

1761

to

1767

region

of

the

HBV

genome.All

detectable

mutations

were

in

the

X-gene

region.AnalysisofHBVMutationsinPMortality

from

Primary

Liver

Cancer

per

100,0000.111010030-3425-2920-2410-1415-1935-3940-441938-421943-47 1953-57 1963-67 1973-77

1983-87Five

Year

Birth

Cohorts1993-9745-4950-5455-5960-

64

years

oldno

vaccination1948-52

1958-62

1968-72

1978-82vaccination1988-92

1998-2002啟東癌癥登記處資料Data

from

Qidong

Cancer

RegistryMost

of

the

decline

in

liver

cancer

has

occurred

in

young

and

middle

age

birth

cohortslikely

vaccinated

in2002as5-10

year

oldsperhaps

25%

vaccinated大部分肝癌的下降出現(xiàn)在中青年出生隊(duì)列中MortalityfromPrimaryLiverCEnvironmental

Exposures

are

Associated

with

Declining

Liver

Cancer

Mortality

in

Qidong環(huán)境暴露物與啟東肝癌死亡率的下降有關(guān)Chen

JG,

Egner

PA

et

al.

CAPR

2013DifferentcohortsEnvironmentalExposuresareAsChen

JG,QDLCI 63Survival

rateSurvival

yearThecomparison

of survivalratesbetween

screening

cohort

and

general

populationin

QidongThe

difference

(effectiveness)

of

early

detection

and

treatment

in

the

field

s