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To the Editor:

We read with great interest the recent report by Li et al.1 analyzing the correlation between the clusters of differentiation 24 (CD24) polymorphism and risk of chronic hepatitis B virus (HBV) infection. In their study, the CD24 P170 T allele (thymidine at position 170) was correlated with a strong, statistically significant increased risk of developing chronic HBV infection. They also showed that CD24 polymorphism may associate with development of hepatocellular carcinoma (HCC). Chronic HBV infection is one of the most important risk factors for HCC. Many patients with chronic HBV infection are more prone to develop liver cirrhosis and HCC when the infection is rampant. In view of these theories, genetic variants underlying chronic HBV infection should be related to HCC susceptibility.

Results of a genome-wide association show the overlapping relation of the Corticotropin-releasing hormone receptor 2 (CRHR2) gene with HCC mediated largely through its association with HBV infection.2 To analyze if CD24 polymorphisms are associated with host susceptibility to HCC, we described a case–control study of 235 cases with HCC and 268 healthy controls in a southeast Chinese population. All patients presented clear histopathological confirmation of HCC. Patients who had preoperative chemotherapy or preoperative chemoradiotherapy were excluded. Population controls were selected from a pool of cancer-free subjects living in the same region as the cases. The control subjects were frequency-matched to the cases on sex and age. The T/T homozygote in CD24 P170 was correlated with a strong, statistically significant increased risk of developing HCC (adjusted odds ratio = 2.96, 95% confidence interval = 1.54-5.79; Table 1). Hence, we proposed that genes underlying a susceptibility to chronic HBV infection may also be relevant to HCC. This result is analogous to the overlapping relation of gene polymorphism with lung cancer that is mediated largely through its association with chronic obstructive pulmonary disease.3

Table 1. Association Between CD24 P170 Genotype and Risk of HCC
GenotypeControl n (%)Case n (%)Crude OR (95% CI)P*Adjusted OR (95% CI)P
  • CI, confidence interval; OR, odds ratio.

  • *

    OR were adjusted by sex.

CC136 (50.7)109 (46.4)1.0 1.0 
CT117 (43.7)90 (38.3)0.96 (0.66-1.39)0.8290.95 (0.65-1.38)0.788
TT15 (5.6)36 (15.3)2.99 (1.56-5.75)0.0012.96 (1.54-5.79)0.001

HCC is one of the most common malignant neoplasms in the world. HBV, hepatitis C virus, excessive alcohol intake, and exposure to aflatoxin B1 are major risk factors for the development of HCC. Approximately 80% of HCC incidence worldwide is etiologically associated with HBV. In view of these facts, HCC is the outcome of chronic inflammation. Genes regulated in local inflammation may be linked with HCC through inflammatory or immune-modulating pathways. Liver inflammation induced by hepatitis B is produced by the cellular immune response against viral antigens present in infected hepatocytes. In this local microenvironment, preneoplastic transformation of hepatocytes is believed to happen. This therefore shows that the CD24 P170 T/T genotype increases the risk of HCC. Genetic factors underlying HBV could be related to HCC risk. Future genome-wide association studies may consider this overlap phenomenon.

References

  1. Top of page
  • 1
    Li D, Zheng L, Jin L, Zhou Y, Li H, Fu J, et al. CD24 polymorphisms affect risk and progression of chronic hepatitis B virus infection. Hepatology 2009; 50: 735-742.
  • 2
    Gu X, Qi P, Zhou F, Ji Q, Wang H, Dou T, et al. An intronic polymorphism in the corticotropin-releasing hormone receptor 2 gene increases susceptibility to HBV-related hepatocellular carcinoma in Chinese population. Hum Genet 2010; 127: 75-81.
  • 3
    Young R, Hopkins R, Etzel C, El-Zein R. Genetics of lung cancer susceptibility and COPD. Lancet Oncol 2011; 12: 622-623.

Liming Sheng M.D.*, Yongjie Shui M.D.*, * Department of Radiation Oncology, Zhejiang Cancer Hospital, Hangzhou, China.