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Chen et al. Hepatoma Res 2018;4:4 I http://dx.doi.org/10.20517/2394-5079.2017.50 Page 7 of 10

[40]
from PLC cases . It was found that around 50% of PLC cases in Qidong had a G to T transversion at the third
position of codon 249 in the P53 gene. Consistent with the results in PLC tissues, the codon 249 mutation
[41]
of P53 was also detected in 46.7% of the plasma samples from PLC patients . Moreover, this mutation was
detected at least 1 year prior to diagnosis in the plasma samples of 4 of 8 cases, suggesting P53 mutation
[42]
could be an early biomarker for PLC . We also have found that PLC risk increased with the elevated
concentration of serum AFB1-albumin adducts, which is a direct biomarker for aflatoxin exposure. Lastly,
a sharp decline in the age-standardized rate of PLC documented by the QCR has occurred subsequent to a
population-scale change in dietary food stuff from maize to corn in the 80s and 90s. The concomitant more
than 1000-fold decline in aflatoxin exposures has occurred well before the implementation of a universal
vaccination program against HBV in this region .
[43]

WHAT ARE THE MAIN STRENGTHS AND WEAKNESS OF THE STUDY?
The main strengths of the QBC are: (1) The QBC is a cohort study with long-term and continuous follow-up,
as well as a very low rate of attrition. To our knowledge, this is a community-based HBV infected cohort
with the longest period of observation worldwide. During the past two decades, the participants of the
cohort have been followed up once or twice each year, which has produced continuous data for research
on PLC etiology. The high quality data from cancer registry and vital statistics of Qidong lend confidence
and perspective to the results. (2) The QBC database comprises a large amount of clinical and laboratory
information. Structured questionnaires were implemented first in 1998 and updated in 2012, which alleviates
concerns that the exposure status of related factors such as smoking and drinking could have changed during
the past two decades. Serum viral and biochemical indicators such as HBsAg, AFP, and ALT at each round
of follow up have been measured by the consistent kits from KHB Company to make longitudinal analysis
possible as is the case with other examination such as abdominal ultrasonography. Although HBV DNA load,
HBeAg, HBV genotype and HBV common mutations were not tested at baseline, they were examined using
archived plasma collected at baseline and from the year when PLC was diagnosed. (3) The bio-sample bank
based on this cohort now has serial plasma, white cell and urine samples. Such valuable samples collected
before and after diagnosis of PLC provide a superior opportunity for evaluation of novel diagnostic markers
of PLC. Indeed, key findings mentioned above were facilitated by availability of longitudinal collection of
plasma samples. To our knowledge, such community-based HBV infected cohorts usually have only baseline
blood samples for each participant. The characteristic of serial samples is exceptional. (4) Although the QBC
is not a large scale cohort, it has already generated 201 PLC cases. This number has surpassed any others of
its kind and will meet the needs of any sophisticated statistical analysis related to the study of PLC etiology
and prognosis.

CAN I GET HOLD OF THE DATA? WHERE CAN I FIND OUT MORE?
The QBC study offers a unique opportunity to further research. Data collection documents and bio-samples
are stored at QDLCI and SCI. We encourage interested research teams to make contact with our current
leader and chief investigator of this cohort, Dr. Tao-Yang Chen, at E-mail: ty110@263.net, and Dr. Hong Tu,
at E-mail: tuhong@shsci.org.

DECLARATIONS
Acknowledgments
We thank Dr. Yawei Zhang from Yale University School of Public Health for her help in the manuscript
preparation. The contribution to data collection made by local physicians, nurses, ultrasound doctors,
interviewers and laboratory staff is greatly and sincerely acknowledged. The authors are also appreciative of
all the senior researchers who have ever worked in the “Qidong high incidence scene of liver cancer”. Only
with their outstanding efforts contributed in the earlier years, could it be realistic for a following generation of