Analysis of Risk Factors for Gastric Cancer and Precancerous Lesions: A Case–Control Study

Abstract

Objectives: To investigate the correlation between gastric xanthoma (GX) and precancerous lesions (PCL) and gastric cancer (GC), and to explore other potential risk factors for PCL and GC in northwest China.

Methods: A case–control study was conducted from September 2022 to September 2023 at Xijing Hospital, Air Force Medical University (Xi’an, Shaanxi Province, China). The patients who underwent gastroscopy were enrolled and divided into the chronic gastritis (CG) group (n = 423), PCL group (n = 422), and GC group (n = 415). The variables were selected through univariate analysis, including demographic information, dietary habits, lifestyle, gastroscopic findings, and Helicobacter pylori (H. pylori) infection. Multivariate logistic regression analysis was performed to analyze the factors associated with PCL and GC, and odds ratio (OR) and 95% confidence interval (CI) were calculated.

Results: GX was more prevalent in the PCL group (14.93%) and the GC group (19.76%) than in the CG group (6.15%). Multivariate analysis revealed that age ≥ 50 years, male gender, rural residence,H. pylori infection, family history of GC, GX, and hypertension were independent risk factors for GC and PCL. Furthermore, a diet high in salt and spice, coupled with daily intake of less than 100 g of fresh fruits, might be associated with the occurrence of GC.

Conclusion: Age ≥ 50 years, male gender, rural residence, family history of GC and H. pylori infection, presence of GX, and a history of hypertension may be risk factors for PCL and GC.

Keywords

chronic gastritis / gastric neoplasms / gastric xanthoma / precancerous lesions

References

[1] F. Bray,M. Laversanne,H. Sung, et al.,“Global Cancer Statistics 2022: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries, ” CA: A Cancer Journal for Clinicians 74, no. 3 (2024):229-263.

[2] R. S. Zhen,S. W. Zhang,K. X. Sun, et al.,“Cancer Statistics in China, 2016, ” Chinese Journal of Oncology 45, no. 3 (2023):212-220. [in Chinese].

[3] A. P. Thrift,T. N. Wenker, and H. B. El-Serag,“Global Burden of Gastric Cancer: Epidemiological Trends, Risk Factors, Screening and Prevention, ” Nature Reviews Clinical Oncology 20, no. 5 (2023):338-349.

[4] H. Møller,E. Heseltine, and H. Vainio,“Working Group Report on Schistosomes, Liver Flukes and Helicobacter pylori, ” International Journal of Cancer 60, no. 5 (1994):587-589.

[5] A. Pormohammad,N. Mohtavinejad,P. Gholizadeh, et al.,“Global Estimate of Gastric Cancer in Helicobacter pylori-Infected Population: A Systematic Review and Meta-Analysis, ” Journal of Cellular Physiology 234, no. 2 (2019):1208-1218.

[6] A. C. Ford,Y. Yuan, and P. Moayyedi,“Helicobacter pylori Eradication Therapy to Prevent Gastric Cancer: Systematic Review and Meta-Analysis, ” Gut 69, no. 12 (2020):2113-2121.

[7] W. Q. Li,J. Y. Zhang,J. L. Ma, et al.,“Effects of Helicobacter pylori Treatment and Vitamin and Garlic Supplementation on Gastric Cancer Incidence and Mortality: Follow-Up of A Randomized Intervention Trial, ” BMJ 366 (2019):l5016.

[8] L. J. Yan,Y. Chen,F. Chen, et al.,“Effect of Helicobacter pylori Eradication on Gastric Cancer Prevention: Updated Report From a Randomized Controlled Trial With 26.5 Years of Follow-Up, ” Gastroenterology 163, no. 1 (2022):154-162.e3.

[9] A. Ş. Köksal,N. Suna,İ. H. Kalkan, et al.,“Is Gastric Xanthelasma an Alarming Endoscopic Marker for Advanced Atrophic Gastritis and Intestinal Metaplasia?, ” Digestive Diseases and Sciences 61, no. 10 (2016):2949-2955.

[10] A. Sekikawa,H. Fukui,T. Maruo, et al.,“Gastric Xanthelasma May Be a Warning Sign for the Presence of Early Gastric Cancer, ” Journal of Gastroenterology and Hepatology 29, no. 5 (2014):951-956.

[11] K. Yamashita,R. Suzuki,T. Kubo, et al.,“Gastric Xanthomas and Fundic Gland Polyps as Endoscopic Risk Indicators of Gastric Cancer, ” Gut Liver 13, no. 4 (2019):409-414.

[12] Y. Chen,X. J. He,M. J. Zhou, and Y. M. Li,“Gastric Xanthelasma and Metabolic Disorders: A Large Retrospective Study Among Chinese Population, ” World Journal of Gastroenterology 23, no. 43 (2017):7756-7764.

[13] D. H. Xiao,X. Tong,X. Q. Yuan,Y. L. Wu, and P. Chen,“Gastric Xanthelasma May Be a Warning Sign of Intestinal Metaplasia: A Cross-Sectional Study, ” Oncology Reports 44, no. 3 (2020):1275-1281.

[14] W. N. Shen,X. D. Qu,S. S. Chen,Y. H. Liu,M. J. Gao, and Y. Q. Shi,“Relationship Between Gastric Xanthoma, Gastric Precancerous Lesions, and Gastric Cancer: A Retrospective Study, ” Journal of Digestive Diseases 24, no. 5 (2023):340-347.

[15] F. F. He,S. M. Wang,R. S. Zheng, et al.,“Trends of Gastric Cancer Burdens Attributable to Risk Factors in China From 2000 to 2050, ” Lancet Regional Health -Western Pacific 44 (2024):101003.

[16] J. He,W. Q. Chen,Z. S. Li, et al.,“China Guideline for the Screening, Early Detection and Early Treatment of Gastric Cancer (2022, Beijing), ” Chinese Journal of Oncology 44, no. 7 (2022):634-666. [in Chinese].

[17] L. Y. Zhang,J. Zhang,D. Li, et al.,“Bile Reflux is an Independent Risk Factor for Precancerous Gastric Lesions and Gastric Cancer: An Observational Cross-Sectional Study, ” Journal of Digestive Diseases 22, no. 5 (2021):282-290.

[18] C. Siccha-Sinti,R. Lewis-Trelles,D. Romaní-Pozo,J. Espinoza-Ríos, and J. Cok,“Prevalence of Histological Types of Gastric Polyps in Adult Patients From a Public Hospital in Lima-Peru (2007-2016), ” Revista de Gastroenterologia del Peru 39, no. 1 (2019):12-20. [in Spanish].

[19] R. T. Hao,L. Qian,B. X. Ye, and L. Zhang,“Study of Association Between Drinking Water and Gastric Cancer of the Residents in Sheyang County Jiangsu Province: A Case-Control Study, ” Chinese Journal of Preventive Medicine 54, no. 8 (2020):892-896.

[20] L. Yang,C. Kartsonaki,P. Yao, et al.,“The Relative and Attributable Risks of Cardia and Non-Cardia Gastric Cancer Associated With Helicobacter pylori Infection in China: A Case-Cohort Study, ” Lancet Public Health 6, no. 12 (2021):e888-e896.

[21] Y. M. Park,J. H. Kim,S. J. Baik,J. J. Park,Y. H. Youn, and H. Park,“Clinical Risk Assessment for Gastric Cancer in Asymptomatic Population After a Health Check-Up: An Individualized Consideration of the Risk Factors, ” Medicine (Baltimore) 95, no. 44 (2016):e5351.

[22] S. Ren,P. P. Cai,Y. Q. Liu, et al.,“Prevalence of Helicobacter pylori Infection in China: A Systematic Review and Meta-Analysis, ” Journal of Gastroenterology and Hepatology 37, no. 3 (2022):464-470.

[23] P. Yuan,L. Lin,K. C. Zheng, et al.,“Risk Factors for Gastric Cancer and Related Serological Levels in Fujian, China: Hospital-Based Case-Control Study, ” BMJ Open 10, no. 9 (2020):e042341.

[24] H. Song,I. G. Ekheden,A. Ploner,J. Ericsson,O. Nyren, and W. Ye,“Family History of Gastric Mucosal Abnormality and the Risk of Gastric Cancer: A Population-Based Observational Study, ” International Journal of Epidemiology 47, no. 2 (2018):440-449.

[25] R. Wu,C. Yang,L. Ji,Z. N. Fan,Y. W. Tao, and Q. Zhan,“Prevalence of Gastric Cancer Precursors in Gastroscopy-Screened Adults by Family History of Gastric Cancer and of Cancers Other Than Gastric, ” BMC Cancer 20, no. 1 (2020):1110.

[26] K. M. Reddy,J. I. Chang,J. M. Shi, and B. U. Wu,“Risk of Gastric Cancer Among Patients With Intestinal Metaplasia of the Stomach in a US Integrated Health Care System, ” Clinical Gastroenterology and Hepatology 14, no. 10 (2016):1420-1425.

[27] M. Jägerstad and K. Skog,“Genotoxicity of Heat-Processed Foods, ” Mutation Research 574, no. 1-2 (2005):156-172.

[28] J. Poorolajal,L. Moradi,Y. Mohammadi,Z. Cheraghi, and F. Gohari-Ensaf,“Risk Factors for Stomach Cancer: A Systematic Review and Meta-Analysis, ” Epidemiology and Health 42 (2020):e2020004.

[29] S. Yan,B. Li,Z. Z. Bai, et al.,“Clinical Epidemiology of Gastric Cancer in Hehuang Valley of China: A 10-Year Epidemiological Study of Gastric Cancer, ” World Journal of Gastroenterology 20, no. 30 (2014):10486-10494.

[30] R. Ofori-Asenso,M. A. Mohsenpour,M. Nouri,S. Faghih,D. Liew, and M. Mazidi,“Association of Spicy Chilli Food Consumption With Cardiovascular and All-Cause Mortality: A Meta-Analysis of Prospective Cohort Studies, ” Angiology 72, no. 7 (2021):625-632.

[31] S. Y. Yi,“Dyslipidemia and H. pylori in Gastric Xanthomatosis, ” World Journal of Gastroenterology 13, no. 34 (2007):4598-4601.

[32] A. Sekikawa,H. Fukui,R. Sada, et al.,“Gastric Atrophy and Xanthelasma are Markers for Predicting the Development of Early Gastric Cancer, ” Journal of Gastroenterology 51, no. 1 (2016):35-42.

[33] N. Shibukawa,S. Ouchi,S. Wakamatsu,Y. Wakahara, and A. Kaneko,“Gastric Xanthoma is a Predictive Marker for Metachronous and Synchronous Gastric Cancer, ” World Journal of Gastrointestinal Oncology 9, no. 8 (2017):327-332.

[34] N. Shibukawa,S. Ouchi,S. Wakamatsu,Y. Wakahara, and A. Kaneko,“Gastric Xanthoma is a Predictive Marker for Early Gastric Cancer Detected After Helicobacter pylori Eradication, ” Internal Medicine 58, no. 6 (2019):779-784.

[35] S. Kitamura,N. Muguruma,K. Okamoto, et al.,“Clinicopathological Assessment of Gastric Xanthoma as Potential Predictive Marker of Gastric Cancer, ” Digestion 96, no. 4 (2017):199-206.

[36] N. Shibukawa,S. Ouchi,S. Wakamatsu,Y. Wakahara, and A. Kaneko,“Gastric Xanthoma is Correlated With Early Gastric Cancer of Previously Helicobacter pylori-Infected Gastric Mucosa, ” JGH Open 5, no. 2 (2021):249-252.

[37] M. Fukushima,H. Fukui,J. Watari, et al.,“Gastric Xanthelasma, Microsatellite Instability and Methylation of Tumor Suppressor Genes in the Gastric Mucosa: Correlation and Comparison as a Predictive Marker for the Development of Synchronous/Metachronous Gastric Cancer, ” Journal of Clinical Medicine 11, no. 1 (2021):9.

[38] E. Kaiserling,H. Heinle,H. Itabe,T. Takano, and W. Remmele,“Lipid Islands in Human Gastric Mucosa: Morphological and Immunohistochemical Findings, ” Gastroenterolog 110, no. 2 (1996):369-374.

[39] S. Petrov,J. Churtchev,R. Mitova,L. Boyanova, and M. Tarassov,“Xanthoma of the Stomach-Some Morphometrical Peculiarities and Scanning Electron Microscopy, ” Hepatogastroenterology 46, no. 26 (1999):1220-1222.

[40] F. Y. Chang,C. Y. Shih, and S. D. Lee,“Abnormal Serum Lipid Levels in Subjects With Gastric Xanthoma, ” Clinica Chimica Acta 217, no. 2 (1993):233-235.

[41] S. Sayar,G. Ayranci,K. Kürbüz, et al.,“High Frequency of Gastric Cancer Precursor Lesions in Patients With Gastric Xanthelasma: A Prospective Case-Control Study, ” European Journal of Gastroenterology & Hepatology 32, no. 9 (2020):1130-1134.

[42] H. Isomoto,Y. Mizuta,K. Inoue, et al.,“A Close Relationship Between Helicobacter pylori Infection and Gastric Xanthoma, ” Scandinavian Journal of Gastroenterology 34, no. 4 (1999):346-352.

[43] S. Hori and Y. Tsutsumi,“Helicobacter pylori Infection in Gastric Xanthomas: Immunohistochemical Analysis of 145 Lesions, ” Pathology International 46, no. 8 (2008):589-593.

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2025 The Author(s). Journal of Digestive Diseases published by Chinese Medical Association Shanghai Branch, Chinese Society of Gastroenterology, Renji Hospital Affiliated to Shanghai Jiaotong University School of Medicine and John Wiley & Sons Australia, Ltd.