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. 2021 Feb 3:9:e10600.
doi: 10.7717/peerj.10600. eCollection 2021.

Liver cancer mortality over six decades in an epidemic area: what we have learned

Jian-Guo Chen  1   2 , Jian Zhu  1 , Yong-Hui Zhang  1 , Yong-Sheng Chen  1 , Jian-Hua Lu  1 , Yuan-Rong Zhu  1 , Hai-Zhen Chen  2 , Ai-Guo Shen  2 , Gao-Ren Wang  2 , John D Groopman  3 , Thomas W Kensler  3   4
Affiliations

Liver cancer mortality over six decades in an epidemic area: what we have learned

Jian-Guo Chen et al. PeerJ. .

Abstract

Background and aims: Liver cancer is one of the most dominant malignant tumors in the world. The trends of liver cancer mortality over the past six decades have been tracked in the epidemic region of Qidong, China. Using epidemiological tools, we explore the dynamic changes in age-standardized rates to characterize important aspects of liver cancer etiology and prevention.

Methods: Mortality data of liver cancer in Qidong from 1958 to 1971 (death retrospective survey) and from 1972 to 2017 (cancer registration) were tabulated for the crude rate (CR), and age-standardized rate and age-birth cohorts. The average annual percentage change was calculated by the Joinpoint Regression Program.

Results: The natural death rate during 1958-2017 decreased from 9‰ to 5.4‰ and then increased to 8‰ as the population aged; cancer mortality rates rose continuously from 57/105 to 240/105. Liver cancer mortality increased from 20/105 to 80/105, and then dropped to less than 52/105 in 2017. Liver cancer deaths in 1972-2017 accounted for 30.53% of all cancers, with a CR of 60.48/105, age-standardized rate China (ASRC) of 34.78/105, and ASRW (world) of 45.71/105. Other key features were the CR for males and females of 91.86/105 and 29.92/105, respectively, with a sex ratio of 3.07:1. Period analysis showed that the ASRs for mortality of the age groups under 54 years old had a significant decreasing trend. Importantly, birth cohort analysis showed that the mortality rate of liver cancer in 40-44, 35-39, 30-34, 25-29, 20-24, 15-19 years cohort decreased considerably, but the rates in 70-74, and 75+ increased.

Conclusions: The crude mortality rate of liver cancer in Qidong has experienced trends from lower to higher levels, and from continued increase at a high plateau to most recently a gradual decline, and a change greatest in younger people. Many years of comprehensive prevention and intervention measures have influenced the decline of the liver cancer epidemic in this area. The reduction of intake levels of aflatoxin might be one of the most significant factors as evidenced by the dramatic decline of exposure biomarkers in this population during the past three decades.

Keywords: Age-standardized rate; Annual percentage change; Birth cohort; Epidemiology; Liver cancer; Mortality; Trend.

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Conflict of interest statement

The authors declare there are no competing interests.

Figures

Figure 1
Figure 1. Natural death rate, mortality rates of cancer and of liver cancer in Qidong, 1958–2017.
Data of 1958–1971 were from a death retrospective survey, while data of 1972–2017 were from cancer registration. Natural death rates in Qidong residents experienced trends from high to low, and to high again; overall cancer mortality rates have shown a continuous increase; whilst liver cancer mortality experienced a dynamic flux from low to high, then sustained at high levels, followed by a gradual decrease in recent years.
Figure 2
Figure 2. AAPC models of ASRW by sex for liver cancer mortality in Qidong, 1972–2017.
Each point represents the actual death rate of liver cancer for males ( formula image), females ( formula image) and both sexes ( formula image). The Joinpoint Regression analysis shows that AAPCs of ASRW were −1.49% for men ( formula image), −1.01% for women ( formula image), and −1.33% for both sexes ( formula image).
Figure 3
Figure 3. The APC of liver cancer mortality in Qidong, 1972–2017.
Each point represents the actual death rate of liver cancer for males ( formula image), females ( formula image) and both sexes ( formula image). Turning point analysis of multiple models shows that the trend in ASRW of liver cancer during the period could be divided into three joinpoints (four periods) for both sexes ( formula image). For men, it was one point (2 periods, formula image), and for women, four joinpoints (5 periods, formula image ).
Figure 4
Figure 4. The average ages of patients with liver cancer in Qidong, 1972–2017.
The mortality rate of liver cancer increased with age. The average age of death from liver cancer in Qidong for both sexes ( formula image), men ( formula image), and women ( formula image).
Figure 5
Figure 5. Age-specific mortality rates of liver cancer by period in Qidong, 1972–2017.
There were significant declining trends for liver cancer mortality rates in all age groups under 54 years old, particularly at age groups of 35–44, 25–34, and 15–24. A slight upward trend in the later period was observed at 55–64, while a slight downward trend was seen at 45–54.
Figure 6
Figure 6. AAPCs of mortality rates of liver cancer by age group in Qidong, 1972–2017.
The Joinpoint Regression analysis shows that the mortality rates at age group of 75+ years, and 65–74 years had significant upwards trends, with AAPC of +3.69%, and +0.95%, respectively. The AAPCs at younger age groups of 55–64, 45–54, and 35–44 had declining trends, being −0.85%, −1.73% and −3.58%, respectively.
Figure 7
Figure 7. Birth-cohort mortality rates of liver cancer in Qidong, 1972–2017.
Birth cohort analysis shows that the mortality of liver cancer in age groups of 15–19, 20–24, 25–29, 30–34, 35–34 and 40–44 displayed downward trends (in the cohorts of “1953” and later births), but showed rising trends in age groups of 70–74, 75–79, 80 and over (in the cohorts before “1938”). Mortality began to show a downward trend in the later periods of the birth cohorts in ages of 45–49, and 50–54
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