Hypercholesterolemia Is an Associated Factor for Risk of Differentiated Thyroid Cancer in Chinese Population

Junyu Zhao, Yutian Tian, Jinming Yao, He Gu, Rui Zhang, Huanjun Wang, Lin Liao, Jianjun Dong, Junyu Zhao, Yutian Tian, Jinming Yao, He Gu, Rui Zhang, Huanjun Wang, Lin Liao, Jianjun Dong

Abstract

Background: Hyperlipidemia has been hypothesized as a risk factor for thyroid cancer. However, the association between hypercholesterolemia and thyroid cancer is unclear, especially in Chinese population without available published data. We conducted this study to investigate the relationship between hypercholesterolemia and differentiated thyroid cancer (DTC) in Chinese population.

Methods: Three thousand seven hundred forty-eight patients were enrolled in the study, including 2,021 DTC patients and 1,727 benign subjects with benign thyroid nodules. Demographic characteristics, medical history, and clinical hematological examination were collected. Stratified analyses of association between hypercholesterolemia and risk of DTC were done. Multivariable logistic regression models were used to estimate the association between hypercholesterolemia and the risk of thyroid nodules being malignant. This study protocol was approved by the ethics committee of Shandong Provincial Qianfoshan Hospital and assigned in ClinicalTrials.gov protocol registration and results system (NCT03006289, https://ichgcp.net/clinical-trials-registry/NCT03006289).

Results: The level of serum total cholesterol in patients with DTC is higher than that in benign subjects (P < 0.001). After adjusting hypercholesterolemia, age (P < 0.001), triglyceride (P = 0.003), and thyroid stimulating hormone (TSH) (P < 0.001) are found to be confounding factors. The risk of DTC in patients younger than 45 years old is 2.08 times than that of patients older than 45 years old (odds ratio = 0.48, 95% CI (0.38, 0.61), P < 0.001). A high TSH level is highly associated with the increased risk of DTC (P < 0.001). The multivariable logistic regression analysis revealed that the absence of hypercholesterolemia could reduce the risk of thyroid nodules being malignant (odds ratio = -0.75, 95% CI (-1.39, -0.12), P = 0.02). Comparing to the higher level of serum total cholesterol (>5.7 mmol/L), the closer the serum total cholesterol level is to normal (3.17-5.7 mmol/L), the less the risk of thyroid nodules being malignant is, and this difference is statistically significant (odds ratio = -0.67, 95% CI (-1.31, -0.03), P = 0.040). However, this difference is not found in the group of patients with lower level of total cholesterol (<3.17 mmol/L, odds ratio = 0.43, 95% CI (-1.22, 2.09), P = 0.068), suggesting that hypocholesterolemia is not a protective factor in the risk of thyroid nodules being malignant.

Conclusions: Hypercholesterolemia is an associated factor for risk of DTC in Chinese population.

Keywords: clinical study; differentiated thyroid cancer; hypercholesterolemia; thyroid nodule; total cholesterol.

Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Copyright © 2021 Zhao, Tian, Yao, Gu, Zhang, Wang, Liao and Dong.

Figures

Figure 1
Figure 1
Distribution of serum total cholesterol levels in patients with DTC and benign thyroid nodules. Serum total cholesterol in the DTC group was significantly higher than that in patients without thyroid carcinoma.

References

    1. Zheng R, Zeng H, Zhang S, Chen W. Estimates of cancer incidence and mortality in China, 2013. Chin J Cancer (2017) 36:66. 10.1186/s40880-017-0234-3
    1. Davies L, Morris LG, Haymart M, Chen AY, Goldenberg D, Morris J, et al. American association of clinical endocrinologists and American college of endocrinology disease state clinical review: The increasing incidence of thyroid cancer. Endocr Pract (2015) 21:686–96. 10.4158/EP14466.DSCR
    1. Tuttle RM, Haddad RI, Ball DW, Byrd D, Dickson P, Duh QY, et al. Thyroid carcinoma, version 2.2014. J Natl Compr Canc Netw (2014) 12:1671–80. 10.6004/jnccn.2014.0169
    1. Jemal A, Bray F, Center MM, Ferlay J, Ward E, Forman D. Global cancer statistics. CA Cancer J Clin (2011) 61:69–90. 10.3322/caac.20107
    1. Sherman SI. Thyroid carcinoma. Lancet (2003) 361:501–11. 10.1016/S0140-6736(03)12488-9
    1. Nagataki S, Nystrom E. Epidemiology and primary prevention of thyroid cancer. Thyroid (2002) 12:889–96. 10.1089/105072502761016511
    1. Boscoe FP, Henry KA, Sherman RL, Johnson CJ. The relationship between cancer incidence, stage and poverty in the United States. Int J Cancer (2016) 139:607–12. 10.1002/ijc.30087
    1. Hung SH, Lin HC, Chung SD. Statin use and thyroid cancer: a population-based case-control study. Clin Endocrinol (Oxf) (2015) 83:111–6. 10.1111/cen.12570
    1. Carey RM, Whelton PK. ACC/AHA Hypertension Guideline Writing Committee. Prevention, Detection, Evaluation, and Management of High Blood Pressure in Adults: Synopsis of the 2017 American College of Cardiology/American Heart Association Hypertension Guideline. Ann Intern Med (2018) 168:351–8. 10.7326/M17-3203
    1. Cruz P, Torres C, Ramírez ME, Epuñán MJ, Valladares LE, Sierralta WD. Proliferation of human mammary cancer cells exposed to 27-hydroxycholesterol. Exp Ther Med (2010) 1:531–6. 10.3892/etm_00000084
    1. Kim JH, Lee J, Jung SY, Kim J. Dietary Factors and Female Breast Cancer Risk: A Prospective Cohort Study. Nutrients (2017) 9:pii: E1331. 10.3390/nu9121331
    1. Lin X, Liu L, Fu Y, Gao J, He Y, Wu Y, et al. Dietary Cholesterol Intake and Risk of Lung Cancer: A Meta-Analysis. Nutrients (2018) 10:pii: E185. 10.3390/nu10020185
    1. Agnoli C, Grioni S, Sieri S, Sacerdote C, Ricceri F, Tumino R, et al. Metabolic syndrome and breast cancer risk: a case-cohort study nested in a multicentre italian cohort. PloS One (2015) 10:e0128891. 10.1371/journal.pone.0128891
    1. Rodrigues Dos Santos C, Fonseca I, Dias S, Mendes de Almeida JC. Plasma level of LDL-cholesterol at diagnosis is a predictor factor of breast tumor progression. BMC Cancer (2014) 14:132. 10.1186/1471-2407-14-132
    1. Ghahremanfard F, Mirmohammadkhani M, Shahnazari B, Gholami G, Mehdizadeh J. The valuable role of measuring serum lipid profile in cancer progression. Oman Med J (2015) 30:353–7. 10.5001/omj.2015.71
    1. Gorin A, Gabitova L, Astsaturov I. Regulation of cholesterol biosynthesis and cancer signaling. Curr Opin Pharmacol (2012) 12:710–6. 10.1016/j.coph.2012.06.011
    1. Wertheim BC, Smith JW, Fang C, Alberts DS, Lance P, Thompson PA. Risk modification of colorectal adenoma by CYP7A1 polymorphisms and the role of bile acid metabolism in carcinogenesis. Cancer Prev Res (Phila) (2012) 5:197–204. 10.1158/1940-6207.CAPR-11-0320
    1. Kitahara CM, Berrington de González A, Freedman ND, Huxley R, Mok Y, Jee SH, et al. Total cholesterol and cancer risk in a large prospective study in Korea. J Clin Oncol (2011) 29:1592–8. 10.1200/JCO.2010.31.5200
    1. Moon H, Ruelcke JE, Choi E, Sharpe LJ, Nassar ZD, Bielefeldt-Ohmann H, et al. Diet-induced hypercholesterolemia promotes androgen-independent prostate cancer metastasis via IQGAP1 and caveolin-1. Oncotarget (2015) 6:7438–53. 10.18632/oncotarget.3476
    1. de Martino M, Leitner CV, Seemann C, Hofbauer SL, Lucca I, Haitel A, et al. Preoperative serum cholesterol is an independent prognostic factor for patients with renal cell carcinoma (RCC). BJU Int (2015) 115:397–404. 10.1111/bju.12767
    1. Wuermli L, Joerger M, Henz S, Schmid HP, Riesen WF, Thomas G, et al. Hypertriglyceridemia as a possible risk factor for prostate cancer. Prostate Cancer Prostatic Dis (2005) 8:316–20. 10.1038/sj.pcan.4500834
    1. Shor R, Wainstein J, Oz D, Boaz M, Matas Z, Fux A, et al. Low serum LDL cholesterol levels and the risk of fever, sepsis, and malignancy. Ann Clin Lab Sci (2007) 37:343–8.
    1. Shor R, Wainstein J, Oz D, Boaz M, Matas Z, Fux A, et al. Low HDL levels and the risk of death, sepsis and malignancy. Clin Res Cardiol (2008) 97:227–33. 10.1007/s00392-007-0611-z
    1. Liu CS, Hsu HS, Li CI, Jan CI, Li TC, Lin WY, et al. Central obesity and atherogenic dyslipidemia in metabolic syndrome are associated with increased risk for colorectal adenoma in a Chinese population. BMC Gastroenterol (2010) 10:51. 10.1186/1471-230X-10-51
    1. Wolk A, Larsson SC, Johansson JE, Ekman P. Long-term fatty fish consumption and renal cell carcinoma incidence in women. JAMA (2006) 296:1371–6. 10.1001/jama.296.11.1371
    1. Pires LA, Hegg R, Freitas FR, Tavares ER, Almeida CP, Baracat EC, et al. Effect of neoadjuvant chemotherapy on low-density lipoprotein (LDL) receptor and LDL receptor-related protein 1 (LRP-1) receptor in locally advanced breast cancer. Braz J Med Biol Res (2012) 45:557–64. 10.1590/S0100-879X2012007500068
    1. Schmid D, Ricci C, Behrens G, Leitzmann MF. Adiposity and risk of thyroid cancer: a systematic review and meta-analysis. Obes Rev (2015) 16:1042–54. 10.1111/obr.12321
    1. Choi JS, Kim EK, Moon HJ, Kwak JY. Higher body mass index may be a predictor of extrathyroidal extension in patients with papillary thyroid microcarcinoma. Endocrine (2015) 48:264–71. 10.1007/s12020-014-0293-z
    1. Jing Z, Hou X, Liu Y, Yan S, Wang R, Zhao S, et al. Association between height and thyroid cancer risk: a meta-analysis of prospective cohort studies. Int J Cancer (2015) 137:1484–90. 10.1002/ijc.29487
    1. Lauby-Secretan B, Scoccianti C, Loomis D, Grosse Y, Bianchini F, Straif K, et al. Body Fatness and Cancer–Viewpoint of the IARC Working Group. N Engl J Med (2016) 375:794–8. 10.1056/NEJMsr1606602
    1. Kitahara CM, Platz EA, Freeman LE, Hsing AW, Linet MS, Park Y, et al. Obesity and thyroid cancer risk among U.S. men and women: a pooled analysis of five prospective studies. Cancer Epidemiol Biomarkers Prev (2011) 20:464–72. 10.1158/1055-9965.EPI-10-1220
    1. Schmid D, Behrens G, Jochem C, Keimling M, Leitzmann M. Physical activity, diabetes, and risk of thyroid cancer: a systematic review and meta-analysis. Eur J Epidemiol (2013) 28:945–58. 10.1007/s10654-013-9865-0

Source: PubMed

3
Abonnieren