Time Trend of Upper Gastrointestinal Cancer Incidence in China from 1990 to 2019 and Analysis Using an Age–Period–Cohort Model

Round 1

Reviewer 1 Report

The authors describe a descriptive study about gastric and esophageal cancers in China. The authors used the Joinpoint software and the age-period-cohort model to investigate the onset trend of gastric and esophageal cancers. Although the manuscript is very informative and written professional manner, there are some concerns that should be addressed.

Major

1. I have to say that it is somehow unusual to investigate the incidence and trend of both gastric and esophageal cancers because their risk factors are different. I understand that the authors want to show the combined data, however, they should show the separate data as well.
2. Introduction. Please clarify the purpose of the present study. Why did the authors analyze the incidence trend of upper gastrointestinal cancer? To show the efficacy of the screening program or to investigate the factors that influence the incidence rate of upper gastrointestinal cancer?
3. Methods. Please describe the information about the institutional review board. 
4. The discussion is written comprehensively, however, it is a bit long to read. Please summarize the discussion.

Minor

1. On page 2, line82, please spell out GBD.
2. If it is possible, the results in table 3 should be shown graphically. 

Author Response

Point 1: I have to say that it is somehow unusual to investigate the incidence and trend of both gastric and esophageal cancers because their risk factors are different. I understand that the authors want to show the combined data, however, they should show the separate data as well.

References:

1. Yang, S; Lin, S.; Li, N; Deng, Y.J.; Wang, M.; Xiang, D.; Xiang, G.; Wang, S.Q.; Ye, X.H.; Zheng,        Y.;et al. Burden, trends, and risk factors of esophageal cancer in China from 1990 to 2017: an      up-to-date overview and comparison with those in Japan and South Korea. J Hematol Oncol.       2020, 13: 146, doi:10.1186/s13045-020-00981-4.
2. Zhang, T.C.; Chen H.; Yin X.L.; He, Q.F.; Man, J.Y.; Yang, X.R.; Lu, M. Changing trends of disease burden of gastric cancer in China from 1990 to 2019 and its predictions: Findings from        Global burden of Disease Study. Chin J Cancer Res. 2021, 33: 11-26,          doi:10.21147/j.issn.1000-9604.2021.01.02.

Point 2: Introduction. Please clarify the purpose of the present study. Why did the authors analyze the incidence trend of upper gastrointestinal cancer? To show the efficacy of the screening program or to investigate the factors that influence the incidence rate of upper gastrointestinal cancer?

Response 2: Thank you for the good point. We mainly took the following three points into account. First: common　risk factors. As you said, the esophageal cancer and gastric cancer have different risk factors. However, they have some common risk factors (e.g., smoking, drinking, high salt diet, moldy or pickled food, and insufficient intake of fruits and vegetables). Second: same　prevalence status. In the past, the above dangerous behaviors were common in Chinese residents, resulting in high prevalence of the esophageal cancer and gastric cancer. Third: identical　prevention and control means. With respect to the prevalence situation of the esophageal cancer and gastric cancer, China conducted the large-scale screening by examining the two adjacent sites, esophagus and stomach, by endoscopy at once. Thus, combining the esophageal cancer and gastric cancer into the upper gastrointestinal cancer can integrate the prevention and treatment resources and help to improve the prevention and treatment efficiency. Combining them both into the upper gastrointestinal cancer for trend analysis facilitates the evaluation of the screening effect.

Point 3: Methods. Please describe the information about the institutional review board.

Response 3: Thank you for pointing this out. Thank you for your suggestion. The editor added the following information "Ethical review and approval were waived for this study, due to the data in this retrospective study are from public database" to the "Institutional Review Board Statement" in the manuscript.

Point 4: The discussion is written comprehensively, however, it is a bit long to read. Please summarize the discussion.

Response 4: Thank you for thoughtful suggestion. We have deleted unnecessary information from the discussion, and made a further summary (second and fourth paragraphs of the discussion section).

Point 5: On page 2, line82, please spell out GBD.

Response 5: Thank you for pointing this out. With respect to the expression of "GBD", we referred to the literatures published by "GBD 2019 Diseases and Injuries Collaborators".

References:

1. GBD 2019 Diseases and Injuries Collaborators. Global burden of 369 diseases and injuries in 204 countries and territories, 1990-2019: a systematic analysis for the Global Burden of Disease Study 2019.Lancet, 2020, 396: 1204-1222, doi: 10.1016/S0140-6736(20)30925-9.

Point 6: If it is possible, the results in table 3 should be shown graphically.

Response 6: This is a good point. We have presented the data from the table graphically (Figure 3).

Reviewer 2 Report

The manuscript by Lin et al submitted to Current Oncology titled: "Time Trend of Upper Gastrointestinal Cancer Incidence in China from 1990 to 2019 and Analysis Using an Age-Period-Cohort Model" is an interesting observational analysis of the trends in upper gastrointestinal cancer over time and age in China.

The reviewer would like to offer a few points for the improvement of the manuscript.

1. The issue of epidemiological transition should be considered by the authors. While recent economic growth indeed could be a reason translating into more pro-hygiene practices thus reducing risk for cancers, however the significant increase of western-diet and processed foods would have the opposite effect. How dietary practices from an epidemiological transition standpoint should be included in the discussion.

2. Along those lines and subsequently when interpreting trends it is important to consider the entire picture of the population including other diseases. For example while the incidence for a certain type of diseases has decreased other diseases. In the case of China T2DM, CVD have certainly increased and these in combination may kill people sooner thus abrogating the effect of a particular cancer type. So it would be helpful if the authors addressed this point in their analysis and discussion. 

3. Moreover, the authors should consider providing the reader with information on other cancer types It appears that the studied type of cancer is reducing its incidence but is this pure or is it because the decrease is replaced by another type(s) of cancer. If that is the case then the arguments of improvement of hygiene may not fully or as strongly explain the reported decrease in incidence.

4. The reviewer would suggest an English native speaker to work on the narrative of the manuscript to improve grammar, syntax and overall flow and use the language.

Author Response

Point 1: The issue of epidemiological transition should be considered by the authors. While recent economic growth indeed could be a reason translating into more pro-hygiene practices thus reducing risk for cancers, however the significant increase of western-diet and processed foods would have the opposite effect. How dietary practices from an epidemiological transition standpoint should be included in the discussion.

Response 1: Thank you for the good point. Indeed, as you said that "the significant increase of western-diet and processed foods would have the opposite effect", we have added these contents to discussion (fifth paragraph of the discussion section). As the dietary pattern of the Chinese residents is westernized gradually, Chinese residents eat more processed and fatty meat, saturated fat, sodium and refined processed sugar. However, the highly unsaturated fat diet would increase the probability of occurrence of gastric cancer.

References:

1. Petrick, J.L.; Steck, S.E.; Bradshaw, P.T.; Trivers, K.F.; Abrahamson, P.E.; Engel, L.S.; He, K.; Chow, W.-H.; Mayne, S.T.; Risch, H.A.; et al. Dietary intake of flavonoids and oesophageal and gastric cancer:     incidence and survival in the United States of America (USA). Br. J. Cancer. 2015, 112, 1291–1300,        doi:10.1038/bjc.2015.25.

Point 2: Along those lines and subsequently when interpreting trends it is important to consider the entire picture of the population including other diseases. For example while the incidence for a certain type of diseases has decreased other diseases. In the case of China T2DM, CVD have certainly increased and these in combination may kill people sooner thus abrogating the effect of a particular cancer type. So it would be helpful if the authors addressed this point in their analysis and discussion.

Response 2: Special thanks to you for your insightful comment. We have added these contents to discussion (sixth paragraph of the discussion section). The incidences of type 2 diabetes mellitus and cardiac-cerebral vascular diseases increase quickly in China, and these diseases and the cancers produce the competing mortality, which possibly leads to the decrease in the incidence of the upper gastrointestinal cancer.

Point 3: Moreover, the authors should consider providing the reader with information on other cancer types It appears that the studied type of cancer is reducing its incidence but is this pure or is it because the decrease is replaced by another type(s) of cancer. If that is the case then the arguments of improvement of hygiene may not fully or as strongly explain the reported decrease in incidence.

Response 3: Thank you for your insightful questions. We have added these contents to discussion (first paragraph of the discussion section). The analysis of the incidence trend of the cancers from 2000 to 2014 in China showed slight increase in the incidences of cancers, among which, the incidences of the colorectal cancer, lung cancer and breast cancer increased quickly, while those of the gastric cancer, esophageal cancer and liver cancer decreased.

References:

1. Zheng, R.S.; Gu, X.Y.; Li, X.T.; Zhang, S.W.; Zeng, H.M.; Sun, K.X.; Zhou, X.N.; Xia, C.F; Yang, Z.X.; Li, H; Chen, W.Q.; He, J. Analysis on the trend of cancer incidence and age change in cancer registry areas        of China, 2000 to 2014. Chin J Prev Med. 2018, 52, 593–600, doi: 10.3760/cma.j.issn.0253-9624.2018.06.007.

Point 4: The reviewer would suggest an English native speaker to work on the narrative of the manuscript to improve grammar, syntax and overall flow and use the language. 

Response 4: Thank you for pointing this out. Before contribution, the manuscript had been submitted to MDPI for English Editing. The Certificate had already been submitted to the contribution system. After we provided your comments, they performed English Editing on the manuscript again.

Round 2

Reviewer 1 Report

The authors revised the manuscript appropriately. 

Thank you.

Reviewer 2 Report

The authors have made a reasonable effort to address reviewer's comments. Proofreading is suggested.