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Association of plasma retinol levels with incident cancer risk in Chinese hypertensive adults: a nested case–control study

  • Liling Xie (a1), Yun Song (a2), Tengfei Lin (a2), Huiyuan Guo (a2), Binyan Wang (a3), Genfu Tang (a3), Chengzhang Liu (a4), Weitong Huang (a5), Yan Yang (a6) (a7), Wenhua Ling (a7) (a8), Yan Zhang (a9), Jianping Li (a9), Yong Huo (a9), Xiaobin Wang (a10), Hao Zhang (a2), Xianhui Qin (a1) and Xiping Xu (a1) (a2) (a3)...

Abstract

We aimed to investigate the association between plasma retinol and incident cancer among Chinese hypertensive adults. We conducted a nested case–control study, including 231 patients with incident cancer and 231 matched controls during a median 4·5-year follow-up of the China Stroke Primary Prevention Trial. There was a significant, inverse association between retinol levels and digestive system cancer (per 10 μg/dl increases: OR 0·79; 95 % CI 0·69, 0·91). When compared with participants in the first quartile of retinol (< 52·3 μg/dl), a significantly lower cancer risk was found in participants in quartile 2–4 ( ≥ 52·3 μg/dl: OR 0·31; 95 % CI 0·13, 0·71). However, there was a U-shaped association between retinol levels and non-digestive system cancers where the risk of cancers decreased (although not significantly) with each increment of plasma retinol (per 10 μg/dl increases: OR 0·89; 95 % CI 0·60, 1·31) in participants with retinol < 68·2 μg/dl, and then increased significantly with retinol (per 10 μg/dl increase: OR 1·65; 95 % CI 1·12, 2·44) in participants with retinol ≥ 68·2 μg/dl. In conclusion, there was a significant inverse dose–response association between plasma retinol and the risk of digestive system cancers. However, a U-shaped association was observed between plasma retinol and the risk of non-digestive cancers (with a turning point approximately 68·2 μg/dl).

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Corresponding author

*Corresponding authors: X. Xu, email xipingxu126@126.com or X. Qin, email pharmaqin@126.com or H. Zhang email zhanghaocau@cau.edu.cn

References

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1.GBD 2013 Mortality and Causes of Death Collaborators (2015) Global, regional, and national age–sex specific all-cause and cause-specific mortality for 240 causes of death, 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 385, 117171.
2.Krinsky, NI & Johnson, EJ (2005) Carotenoid actions and their relation to health and disease. Mol Aspects Med 26, 459516.
3.Harrison, EH (2012) Mechanisms involved in the intestinal absorption of dietary vitamin A and provitamin A carotenoids. Biochim Biophys Acta Mol Cell Biol Lipids 1821, 7077.
4.Sporn, MB (1983) Role of retinoids in differentiation and carcinogenesis. Cancer Res 43, 30343040.
5.Gudas, LJ & Wagner, JA (2011) Retinoids regulate stem cell differentiation. J Cell Physiol 226, 322330.
6.Altucci, L & Gronemeyer, H (2001) The promise of retinoids to fight against cancer. Nat Rev Cancer 1, 181193.
7.Edem, DO (2009) Vitamin A: a review. Asia Pac J Clin Nutr 1, 65–82.
8.Abnet, CC, Qiao, YL, Dawsey, SM, et al. (2003) Prospective study of serum retinol, beta-carotene, beta-cryptoxanthin, and lutein/zeaxanthin and esophageal and gastric cancers in China. Cancer Causes Control 14, 645655.
9.Yuan, JM, Ross, RK, Gao, YT, et al. (2004) Prediagnostic levels of serum micronutrients in relation to risk of gastric cancer in Shanghai, China. Cancer Epidemiol Biomarkers Prev 13, 17721780.
10.Jenab, M, Riboli, E, Ferrari, P, et al. (2006) Plasma and dietary carotenoid, retinol and tocopherol levels and the risk of gastric adenocarcinomas in the European prospective investigation into cancer and nutrition. Br J Cancer 95, 406415.
11.Persson, C, Sasazuki, S, Inoue, M, et al. (2008) Plasma levels of carotenoids, retinol and tocopherol and the risk of gastric cancer in Japan: a nested case–control study. Carcinogenesis 29, 10421048.
12.Lai, GY, Weinstein, SJ, Albanes, D, et al. (2014) Association of serum alpha-tocopherol, beta-carotene, and retinol with liver cancer incidence and chronic liver disease mortality. Br J Cancer 111, 21632171.
13.Yu, MW, Hsieh, HH, Pan, WH, et al. (1995) Vegetable consumption, serum retinol level, and risk of hepatocellular carcinoma. Cancer Res 55, 1301–51305.
14.Yuan, JM, Gao, YT, Ong, CN, et al. (2006) Prediagnostic level of serum retinol in relation to reduced risk of hepatocellular carcinoma. J Natl Cancer Inst 98, 482490.
15.Mondul, AM, Watters, JL, Mannisto, S, et al. (2011) Serum retinol and risk of prostate cancer. Am J Epidemiol 173, 813821.
16.Key, TJ, Appleby, PN, Travis, RC, et al. (2015) Carotenoids, retinol, tocopherols, and prostate cancer risk: pooled analysis of 15 studies. Am J Clin Nutr 102, 1142–1157.
17.Maillard, V, Kuriki, K, Lefebvre, B, et al. (2010) Serum carotenoid, tocopherol and retinol concentrations and breast cancer risk in the E3N-EPIC study. Int J Cancer 127, 11881196.
18.Pouchieu, C, Galan, P, Ducros, V, et al. (2014) Plasma carotenoids and retinol and overall and breast cancer risk: a nested case-control study. Nutr Cancer 66, 980–988.
19.Hu, F, Wu, Z, Li, G, et al. (2015) The plasma level of retinol, vitamins a, C and α-tocopherol could reduce breast cancer risk? A meta-analysis and meta-regression. J Cancer Res Clin 141, 601614.
20.Willett, WC, Polk, BF, Underwood, BA, et al. (1984) Relation of serum vitamins A and E and carotenoids to the risk of cancer. N Engl J Med 310, 430434.
21.Coates, RJ, Weiss, NS, Daling, JR, et al. (1988) Serum levels of selenium and retinol and the subsequent risk of cancer. Am J Epidemiol 128, 515523.
22.Peleg, I, Heyden, S, Knowles, M, et al. (1984) Serum retinol and risk of subsequent cancer: extension of the Evans County, Georgia, study. J Natl Cancer Inst 73, 14551458.
23.Knekt, P, Aromaa, A, Maatela, J, et al. (1990) Serum vitamin A and subsequent risk of cancer: cancer incidence follow-up of the Finnish Mobile Clinic Health Examination Survey. Am J Epidemiol 132, 857870.
24.Huo, Y, Li, J, Qin, X, et al. (2015) Efficacy of folic acid therapy in primary prevention of stroke among adults with hypertension in China: the CSPPT randomized clinical trial. JAMA 313, 13251335.
25.Qin, X, Li, J, Spence, JD, et al. (2016) Folic acid therapy reduces the first stroke risk associated with hypercholesterolemia among hypertensive patients. Stroke 47, 28052812.
26.Xu, RB, Kong, X, Xu, BP, et al. (2017) Longitudinal association between fasting blood glucose concentrations and first stroke in hypertensive adults in China: effect of folic acid intervention. Am J Clin Nutr 105, 564570.
27.Zhao, M, Wang, X, He, M, et al. (2017) Homocysteine and stroke risk: modifying effect of Methylenetetrahydrofolate Reductase C677T Polymorphism and Folic Acid Intervention. Stroke 48, 11831190.
28.Kong, X, Huang, X, Zhao, M, et al. (2018) Platelet count affects efficacy of folic acid in preventing first stroke. J Am Coll Cardiol 71, 21362146.
29.Xu, X, Qin, X, Li, Y, et al. (2016) Efficacy of folic acid therapy on the progression of chronic kidney disease. JAMA Intern Med 176, 1443.
30.Li, Y, Qin, X, Luo, L, et al. (2017) Folic acid therapy reduces the risk of mortality associated with heavy proteinuria among hypertensive patients. J Hypertens 35, 13021309.
31.Li, Y, Liang, M, Wang, G, et al. (2017) Effects of folic acid therapy on the New-Onset proteinuria in Chinese hypertensive patients. Hypertension 70, 300306.
32.Qin, X, Li, Y, He, M, et al. (2017) Folic acid therapy reduces serum uric acid in hypertensive patients: a substudy of the China Stroke Primary Prevention Trial (CSPPT). Am J Clin Nutr 105, 882889.
33.Qin, X, Li, J, Zhang, Y, et al. (2016) Effect of folic acid supplementation on risk of new-onset diabetes in adults with hypertension in China: findings from the China Stroke Primary Prevention Trial (CSPPT). J Diabetes 8, 286294.
34.Qin, X, Shen, L, Zhang, R, et al. (2017) Effect of folic acid supplementation on cancer risk among adults with hypertension in China: a randomized clinical trial. Int J Cancer 141, 837847.
35.Qin, X, Li, Y, Sun, N, et al. (2017) Elevated homocysteine concentrations decrease the antihypertensive effect of Angiotensin-Converting enzyme inhibitors in hypertensive patients. Arterioscler Thromb Vasc Biol 37, 166172.
36.Yu, Y, Zhang, H, Song, Y, et al. (2019) Plasma retinol and the risk of first stroke in hypertensive adults: a nested case-control study. Am J Clin Nutr 109, 449456.
37.Omenn, GS, Goodman, GE, Thornquist, MD, et al. (1996) Effects of a combination of beta carotene and vitamin A on lung cancer and cardiovascular disease. N Engl J Med 334, 11501155.
38.Goodman, GE, Thornquist, MD, Balmes, J, et al. (2004) The Beta-Carotene and Retinol Efficacy Trial: incidence of lung cancer and cardiovascular disease mortality during 6-year follow-up after stopping beta-carotene and retinol supplements. J Natl Cancer Inst 96, 17431750.
39.Palace, VP, Khaper, N, Qin, Q, et al. (1999) Antioxidant potentials of vitamin A and carotenoids and their relevance to heart disease. Free Radic Biol Med 26, 746761.
40.Halliwell, B, Zhao, K & Whiteman, M (2000) The gastrointestinal tract: a major site of antioxidant action? Free Radic Res 33, 819830.
41.Leo, MA &Lieber, CS (1999) Alcohol, vitamin A, and beta-carotene: adverse interactions, including hepatotoxicity and carcinogenicity. Am J Clin Nutr 69, 10711085.
42.Rothman, KJ, Moore, LL, Singer, MR, et al. (1995) Teratogenicity of high vitamin A intake. N Engl J Med 333, 13691373.
43.Melhus, H, Michaelsson, K, Kindmark, A, et al. (1998) Excessive dietary intake of vitamin A is associated with reduced bone mineral density and increased risk for hip fracture. Ann Intern Med 129, 770778.
44.Colbert, MC (2002) Retinoids and cardiovascular developmental defects. Cardiovasc Toxicol 2, 2539.
45.Biesalski, HK (1989) Comparative assessment of the toxicology of vitamin A and retinoids in man. Toxicology 57, 117161.
46.Hathcock, JN, Hattan, DG, Jenkins, MY, et al. (1990) Evaluation of vitamin A toxicity. Am J Clin Nutr 52, 183202.
47.Du, W, Wang, H, Wang, Z, et al. (2018) Dietary vitamin an intake among Chinese adults: findings from CNTCS2015. Nutr J 17, 60.

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