Abstract: Objective To investigate genetic changes in individuals that may influence development of hepatocellular carcinoma （HCC） associated with hepatitis B virus（HBV）and exposure to aflatoxin B₁ （AFB₁）. Method Patients with HCC were divided into four groups based on HBV infection and AFB₁ exposure status：HBV（+）/AFB₁（+），n=10； HBV（+）/AFB₁（-），n=10； HBV（-）/AFB₁（+）， n=6； HBV（-）/AFB₁（-），n=6.Array-based comparative genomic hybridization（Array CGH） was carried out on tumor tissue to identify genome-wide genetic changes. Result Among all 32 tissue samples，573 CNAs were identified， comprising 184 gains and 389 losses. Frequent gains were observed in the following regions： 1q，4p，5p，6p，7p，8q，10p，17q，20p，20q and X.Frequent losses were observed in the following regions：1p，2q，4q，8p，9p，10q，11q，13q，14q，16p，16q，17p，19p，19q，21q，22q and Y.A total of 25 RARs were de-tected： 8 RAR gains were 1q21.1-q44，5p13.2-p15.3，6p12.1-p25.2，7q21.1-q35，8q11.2-q24.3，17q12-q25.2，18q12.3-q22.3 and X； 17 RARs losses were 1p31.1-p36.2，2q23.2-q37.2，4q12-q35.2，6q14.1-q26，8p12-p23.2，9p21.1-p24.2，10q21.3-q26.2，13q12.1-q21.1， 14q21.3-q32.2，16p12.1-p13.2，16q12.1-q24.1，17p12-p13.3，19p13.1-p13.3，19q13.2-q13.4，21q21.3-q22.2，22q11.2-q13.2 and Y.Loss of 8p12-p23.2 was associated with higher TNM tumor stage（TNM Ⅰ-Ⅱ： 38.9% vs TNM Ⅲ：92.9%；P=0.038） and shorter tumor-free survival （P=0.045）.Loss of 4q13.3-q35.2 and 13q12.1-q21.2 and gain of 7q11.2-q35 occurred at higher frequency among HBV（+）/AFB₁（+） patients than among the other groups. Univariate analysis found tumor-free survival to be associated with tumor size， serum AFP，BCLC，TNM stage，invasion and metastasis，and loss of 8p12-p23.2（all P<0.05）.Multivariate analysis revealed three of these fac-tors to be independently associated with tumor-free survival：serum AFP（≥400），TNM stage， and loss of 8p12-p23.2（all P≤0.045）. Conclusion Several chromosomal alterations were identified in the genomes of individuals with HCC in Guangxi.Loss of 19p13.1-p13.3 may be a characteristic feature of the disease in this part of China. Loss of 8p12-p23.2 may occur later during HCC progression and is associated with shorter tumor-free survival. Loss of 4q12-q35.2 and 13q12.1-q21.1 and gain of 7q21.1-q35 may be associated with the synergistic hepatocarcinogenic effect of HBV infection combined with AFB1 exposure.

Key words:  Liver neoplasms, Hepatitis B virus, Aflatoxin B1, Chromosome, Array CGH