Relation between serum total cholesterol and risk of gastric cancer: a systematic review and meta-analysis_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

LIU Shuo ^1,2,3 , ZHU Lihui ^2,3,4 , LIAO Tianyi ^1,2,3 , ZHANG Xiang ^1,2,3 ,  CAI Hui ^1,2,3,4

1. The First Clinical Medical College, Lanzhou University, Lanzhou 730000, P. R. China;
2. Gansu Provincial Hospital, Lanzhou 730099, P. R. China;
3. Key Laboratory of Molecular Diagnosis and Precision Medicine for Surgical Oncology in Gansu Province, Lanzhou 730000, P. R. China;
4. School of Clinical Medicine, Ningxia Medical University, Yinchuan 750004, P. R. China;

Corresponding author：

CAI Hui, Email: caialonteam@163.com

Keywords：

gastric cancer; total cholesterol; meta-analysis; risk factors

DOI：

10.7507/1007-9424.202306042

Video：

Export PDF Favorites Scan Get Citation

Abstract Full text Figures/Tables Video References Cited by

Objective To conduct a systematical evaluation and meta-analysis of the relation between serum total cholesterol (TC) level and the risk of gastric cancer. Methods The PubMed, Embase, Web of Science, and Cochrane Library databases were searched from inception to March 5, 2023. Two independent reviewers performed the literature search, identification, and screening, as well as performed the quality assessment and data extraction. Results A total of 12 studies with 5 143 671 participants and 40 551 patients with gastric cancer were included in the meta-analysis. The results of meta analysis showed that 9 studies reported that the elevated serum TC level decreased the risk of gastric cancer [OR (95%CI) was 0.91 (0.85, 0.98)], and 5 studies reported that the decreased serum TC level increased the risk of gastric cancer [OR (95%CI) was 1.93 (1.17, 3.18)]. Also the results of the subgroup analyses showed that the decreased serum TC level increased the risk of gastric cancer in the studies with cohort study, larger overall sample sizes and gastric cancer sample sizes, with longer duration of follow-up, and in those with habits of alcohol and smoking [0.89 (0.87, 0.92), 0.90 (0.87, 0.94), 0.90 (0.87, 0.93), 0.86 (0.82, 0.90), 0.90 (0.87, 0.93), and 0.90 (0.87, 0.93), respectively] , which was consistent with the overall results. In contrast, there was no statistical difference in the relation between the elevated serum TC level decreased the risk of gastric cancer between male and female patients in the gender subgroup. Conclusions The results of this systematical evaluation and meta-analysis suggest that serum TC level [135–294 mg/dL (3.49–7.62 mmol/L)] may be a protective factor for gastric carcinogenesis. The risk of gastric carcinogenesis may be increased when serum TC level decreases, and this change is a long-term and insidious process.

Citation： LIU Shuo, ZHU Lihui, LIAO Tianyi, ZHANG Xiang, CAI Hui. Relation between serum total cholesterol and risk of gastric cancer: a systematic review and meta-analysis. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2023, 30(10): 1232-1238. doi: 10.7507/1007-9424.202306042 Copy

1.	Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2.	张振山, 姚天宇, 许迪. 幽门螺旋杆菌抗体、胃蛋白酶原、促胃液素-17与胃癌临床分期的相关性. 医学研究与教育, 2022, 39(6): 29-34.
3.	Thrift AP, El-Serag HB. Burden of gastric cancer. Clin Gastroenterol Hepatol, 2020, 18(3): 534-542.
4.	王罡强, 袁金秋, 张常华, 等. 代谢综合征及其组分与胃癌发生风险前瞻性队列研究. 热带医学杂志, 2021, 21(9): 1096-1102.
5.	Huang D, Shin WK, De la Torre K, et al. Association between metabolic syndrome and gastric cancer risk: results from the Health Examinees Study. Gastric Cancer, 2023, 26(4): 481-492.
6.	Li H, Feng Z, He ML. Lipid metabolism alteration contributes to and maintains the properties of cancer stem cells. Theranostics, 2020, 10(16): 7053-7069.
7.	Touvier M, Fassier P, His M, et al. Cholesterol and breast cancer risk: a systematic review and meta-analysis of prospective studies. Br J Nutr, 2015, 114(3): 347-357.
8.	周星辰, 张惟纲, 赵昆, 等. 结直肠癌胆固醇代谢及相关治疗研究进展. 中华肿瘤防治杂志, 2023, 30(8): 497-502.
9.	Song YM, Sung J, Kim JS. Which cholesterol level is related to the lowest mortality in a population with low mean cholesterol level: a 6.4-year follow-up study of 482 472 Korean men. Am J Epidemiol, 2000, 151(8): 739-747.
10.	Pih GY, Gong EJ, Choi JY, et al. Associations of serum lipid level with gastric cancer risk, pathology, and prognosis. Cancer Res Treat, 2021, 53(2): 445-456.
11.	Lindkvist B, Almquist M, Bjørge T, et al. Prospective cohort study of metabolic risk factors and gastric adenocarcinoma risk in the Metabolic Syndrome and Cancer Project (Me-Can). Cancer Causes Control, 2013, 24(1): 107-116.
12.	Gong EJ, Ahn JY, Jung HY, et al. Risk factors and clinical outcomes of gastric cancer identified by screening endoscopy: a case-control study. J Gastroenterol Hepatol, 2014, 29(2): 301-309.
13.	Lim JH, Shin CM, Han K, et al. Nationwide cohort study: cholesterol level is inversely related with the risk of gastric cancer among postmenopausal women. Gastric Cancer, 2022, 25(1): 11-21.
14.	Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ, 2021, 372: n71.
15.	Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
16.	Peters JL, Sutton AJ, Jones DR, et al. Comparison of two methods to detect publication bias in meta-analysis. JAMA, 2006, 295(6): 676-680.
17.	van Enst WA, Ochodo E, Scholten RJ, et al. Investigation of publication bias in meta-analyses of diagnostic test accuracy: a meta-epidemiological study. BMC Med Res Methodol, 2014, 14: 70.
18.	Törnberg SA, Carstensen JM, Holm LE. Risk of stomach cancer in association with serum cholesterol and beta-lipoprotein. Acta Oncol, 1988, 27(1): 39-42.
19.	Eichholzer M, Stähelin HB, Gutzwiller F, et al. Association of low plasma cholesterol with mortality for cancer at various sites in men: 17-y follow-up of the prospective Basel study. Am J Clin Nutr, 2000, 71(2): 569-574.
20.	Asano K, Kubo M, Yonemoto K, et al. Impact of serum total cholesterol on the incidence of gastric cancer in a population-based prospective study: the Hisayama study. Int J Cancer, 2008, 122(4): 909-914.
21.	Iso H, Ikeda A, Inoue M, et al. Serum cholesterol levels in relation to the incidence of cancer: the JPHC study cohorts. Int J Cancer, 2009, 125(11): 2679-2686.
22.	Ahn J, Lim U, Weinstein SJ, et al. Prediagnostic total and high-density lipoprotein cholesterol and risk of cancer. Cancer Epidemiol Biomarkers Prev, 2009, 18(11): 2814-2821.
23.	Kitahara CM, Berrington de González A, Freedman ND, et al. Total cholesterol and cancer risk in a large prospective study in Korea. J Clin Oncol, 2011, 29(12): 1592-1598.
24.	Kang R, Li P, Wang T, et al. Apolipoprotein E epsilon 2 allele and low serum cholesterol as risk factors for gastric cancer in a Chinese Han population. Sci Rep, 2016, 6: 19930.
25.	Trichopoulou A, Lagiou P, Kuper H, et al. Cancer and mediterranean dietary traditions. Cancer Epidemiol Biomarkers Prev, 2000, 9(9): 869-873.
26.	Hajjar M, Rezazadeh A. Recommended food score and healthy nordic food index in cancer: a systematic review. Nutr Cancer, 2021, 73(3): 369-375.
27.	Ur Rahman MS, Cao J. Estrogen receptors in gastric cancer: advances and perspectives. World J Gastroenterol, 2016, 22(8): 2475-2482.
28.	Abdalkareem Jasim S, Kzar HH, Haider Hamad M, et al. The emerging role of 27-hydroxycholesterol in cancer development and progression: an update. Int Immunopharmacol, 2022, 110: 109074.
29.	Yamauchi Y, Rogers MA. Sterol metabolism and transport in atherosclerosis and cancer. Front Endocrinol (Lausanne), 2018, 9: 509.
30.	Calleros L, Lasa M, Toro MJ, et al. Low cell cholesterol levels increase NFkappaB activity through a p38 MAPK-dependent mechanism. Cell Signal, 2006, 18(12): 2292-2301.
31.	Radišauskas R, Kuzmickienė I, Milinavičienė E, et al. Hypertension, serum lipids and cancer risk: a review of epidemiological evidence. Medicina (Kaunas), 2016, 52(2): 89-98.
32.	Murai T. Cholesterol lowering: role in cancer prevention and treatment. Biol Chem, 2015, 396(1): 1-11.
33.	Ravnskov U, McCully KS, Rosch PJ. The statin-low cholesterol-cancer conundrum. QJM, 2012, 105(4): 383-388.
34.	Strohmaier S, Edlinger M, Manjer J, et al. Total serum cholesterol and cancer incidence in the Metabolic syndrome and Cancer Project (Me-Can). PLoS One, 2013, 8(1): e54242.
35.	Huxley R, Lewington S, Clarke R. Cholesterol, coronary heart disease and stroke: a review of published evidence from observational studies and randomized controlled trials. Semin Vasc Med, 2002, 2(3): 315-323.
36.	Toner CD, Davis CD, Milner JA. The vitamin D and cancer conundrum: aiming at a moving target. J Am Diet Assoc, 2010, 110(10): 1492-1500.
37.	Ma X, Bi E, Lu Y, et al. Cholesterol induces CD8⁺ T cell exhaustion in the tumor microenvironment. Cell Metab, 2019, 30(1): 143-156.
38.	King RJ, Singh PK, Mehla K. The cholesterol pathway: impact on immunity and cancer. Trends Immunol, 2022, 43(1): 78-92.

1. Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin, 2021, 71(3): 209-249.
2. 张振山, 姚天宇, 许迪. 幽门螺旋杆菌抗体、胃蛋白酶原、促胃液素-17与胃癌临床分期的相关性. 医学研究与教育, 2022, 39(6): 29-34.
3. Thrift AP, El-Serag HB. Burden of gastric cancer. Clin Gastroenterol Hepatol, 2020, 18(3): 534-542.
4. 王罡强, 袁金秋, 张常华, 等. 代谢综合征及其组分与胃癌发生风险前瞻性队列研究. 热带医学杂志, 2021, 21(9): 1096-1102.
5. Huang D, Shin WK, De la Torre K, et al. Association between metabolic syndrome and gastric cancer risk: results from the Health Examinees Study. Gastric Cancer, 2023, 26(4): 481-492.
6. Li H, Feng Z, He ML. Lipid metabolism alteration contributes to and maintains the properties of cancer stem cells. Theranostics, 2020, 10(16): 7053-7069.
7. Touvier M, Fassier P, His M, et al. Cholesterol and breast cancer risk: a systematic review and meta-analysis of prospective studies. Br J Nutr, 2015, 114(3): 347-357.
8. 周星辰, 张惟纲, 赵昆, 等. 结直肠癌胆固醇代谢及相关治疗研究进展. 中华肿瘤防治杂志, 2023, 30(8): 497-502.
9. Song YM, Sung J, Kim JS. Which cholesterol level is related to the lowest mortality in a population with low mean cholesterol level: a 6.4-year follow-up study of 482 472 Korean men. Am J Epidemiol, 2000, 151(8): 739-747.
10. Pih GY, Gong EJ, Choi JY, et al. Associations of serum lipid level with gastric cancer risk, pathology, and prognosis. Cancer Res Treat, 2021, 53(2): 445-456.
11. Lindkvist B, Almquist M, Bjørge T, et al. Prospective cohort study of metabolic risk factors and gastric adenocarcinoma risk in the Metabolic Syndrome and Cancer Project (Me-Can). Cancer Causes Control, 2013, 24(1): 107-116.
12. Gong EJ, Ahn JY, Jung HY, et al. Risk factors and clinical outcomes of gastric cancer identified by screening endoscopy: a case-control study. J Gastroenterol Hepatol, 2014, 29(2): 301-309.
13. Lim JH, Shin CM, Han K, et al. Nationwide cohort study: cholesterol level is inversely related with the risk of gastric cancer among postmenopausal women. Gastric Cancer, 2022, 25(1): 11-21.
14. Page MJ, McKenzie JE, Bossuyt PM, et al. The PRISMA 2020 statement: an updated guideline for reporting systematic reviews. BMJ, 2021, 372: n71.
15. Stang A. Critical evaluation of the Newcastle-Ottawa scale for the assessment of the quality of nonrandomized studies in meta-analyses. Eur J Epidemiol, 2010, 25(9): 603-605.
16. Peters JL, Sutton AJ, Jones DR, et al. Comparison of two methods to detect publication bias in meta-analysis. JAMA, 2006, 295(6): 676-680.
17. van Enst WA, Ochodo E, Scholten RJ, et al. Investigation of publication bias in meta-analyses of diagnostic test accuracy: a meta-epidemiological study. BMC Med Res Methodol, 2014, 14: 70.
18. Törnberg SA, Carstensen JM, Holm LE. Risk of stomach cancer in association with serum cholesterol and beta-lipoprotein. Acta Oncol, 1988, 27(1): 39-42.
19. Eichholzer M, Stähelin HB, Gutzwiller F, et al. Association of low plasma cholesterol with mortality for cancer at various sites in men: 17-y follow-up of the prospective Basel study. Am J Clin Nutr, 2000, 71(2): 569-574.
20. Asano K, Kubo M, Yonemoto K, et al. Impact of serum total cholesterol on the incidence of gastric cancer in a population-based prospective study: the Hisayama study. Int J Cancer, 2008, 122(4): 909-914.
21. Iso H, Ikeda A, Inoue M, et al. Serum cholesterol levels in relation to the incidence of cancer: the JPHC study cohorts. Int J Cancer, 2009, 125(11): 2679-2686.
22. Ahn J, Lim U, Weinstein SJ, et al. Prediagnostic total and high-density lipoprotein cholesterol and risk of cancer. Cancer Epidemiol Biomarkers Prev, 2009, 18(11): 2814-2821.
23. Kitahara CM, Berrington de González A, Freedman ND, et al. Total cholesterol and cancer risk in a large prospective study in Korea. J Clin Oncol, 2011, 29(12): 1592-1598.
24. Kang R, Li P, Wang T, et al. Apolipoprotein E epsilon 2 allele and low serum cholesterol as risk factors for gastric cancer in a Chinese Han population. Sci Rep, 2016, 6: 19930.
25. Trichopoulou A, Lagiou P, Kuper H, et al. Cancer and mediterranean dietary traditions. Cancer Epidemiol Biomarkers Prev, 2000, 9(9): 869-873.
26. Hajjar M, Rezazadeh A. Recommended food score and healthy nordic food index in cancer: a systematic review. Nutr Cancer, 2021, 73(3): 369-375.
27. Ur Rahman MS, Cao J. Estrogen receptors in gastric cancer: advances and perspectives. World J Gastroenterol, 2016, 22(8): 2475-2482.
28. Abdalkareem Jasim S, Kzar HH, Haider Hamad M, et al. The emerging role of 27-hydroxycholesterol in cancer development and progression: an update. Int Immunopharmacol, 2022, 110: 109074.
29. Yamauchi Y, Rogers MA. Sterol metabolism and transport in atherosclerosis and cancer. Front Endocrinol (Lausanne), 2018, 9: 509.
30. Calleros L, Lasa M, Toro MJ, et al. Low cell cholesterol levels increase NFkappaB activity through a p38 MAPK-dependent mechanism. Cell Signal, 2006, 18(12): 2292-2301.
31. Radišauskas R, Kuzmickienė I, Milinavičienė E, et al. Hypertension, serum lipids and cancer risk: a review of epidemiological evidence. Medicina (Kaunas), 2016, 52(2): 89-98.
32. Murai T. Cholesterol lowering: role in cancer prevention and treatment. Biol Chem, 2015, 396(1): 1-11.
33. Ravnskov U, McCully KS, Rosch PJ. The statin-low cholesterol-cancer conundrum. QJM, 2012, 105(4): 383-388.
34. Strohmaier S, Edlinger M, Manjer J, et al. Total serum cholesterol and cancer incidence in the Metabolic syndrome and Cancer Project (Me-Can). PLoS One, 2013, 8(1): e54242.
35. Huxley R, Lewington S, Clarke R. Cholesterol, coronary heart disease and stroke: a review of published evidence from observational studies and randomized controlled trials. Semin Vasc Med, 2002, 2(3): 315-323.
36. Toner CD, Davis CD, Milner JA. The vitamin D and cancer conundrum: aiming at a moving target. J Am Diet Assoc, 2010, 110(10): 1492-1500.
37. Ma X, Bi E, Lu Y, et al. Cholesterol induces CD8⁺ T cell exhaustion in the tumor microenvironment. Cell Metab, 2019, 30(1): 143-156.
38. King RJ, Singh PK, Mehla K. The cholesterol pathway: impact on immunity and cancer. Trends Immunol, 2022, 43(1): 78-92.

CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Relation between serum total cholesterol and risk of gastric cancer: a systematic review and meta-analysis

Abstract Full text Figures/Tables Video References Cited by

Previous Article

Next Article

Format

Content