Skip to main content

Risk of uterine leiomyoma based on BET1L rs2280543 single nucleotide polymorphism and vegetarian diet

Abstract

Background

Bet1 Golgi vesicular membrane trafficking protein-like (BET1L) rs2280543 single nucleotide polymorphism (SNP) and diet have been independently associated with uterine leiomyoma (UL). However, whether the SNP and diet could jointly influence the risk of UL is yet to be assessed. Therefore, we investigated the independent and interactive effects of vegetarian diet and BET1L rs2280543 on uterine fibroids in Taiwanese women.

Methods

We linked participants’ electronic data in the Taiwan Biobank (TWB) database to their medical records in the National Health Insurance Research Database (NHIRD). The TWB had genotypic, lifestyle, and biochemical data between 2008 and 2015 and the NHIRD had data on disease diagnoses between 1998 and 2015. In this study, we included 1997 premenopausal women with complete data.

Results

Compared  to participants with the BET1L rs2280543 CC genotype (wildtype), those with CT/CC genotype had an odds ratio (OR) of 0.69 and a 95% confidence interval (CI) of 0.51–0.93. Vegetarian diet and UL were not significantly associated: OR = 1.09 and 95% CI = 0.77–1.55. However, the test for interaction between rs2280543 and vegetarian diet was significant (p = 0.046). Compared to individuals with the CC genotype, the risk of UL was lower among vegetarians with the CT/TT genotype: OR (95% CI) = 0.15 (0.05–0.47).

Conclusion

The BET1L rs2280543 CT/TT genotype was associated with a lower risk of UL especially among vegetarians.

Peer Review reports

Introduction

Uterine fibroids (UFs) or uterine leiomyomas (ULs) are benign tumors caused by excessive growth of the uterine smooth muscle and connective tissue [1]. They are associated with significant morbidity and poor quality of life [2]. Environmental and genetic factors contribute to the pathogenesis of UL [2,3,4,5,6,7,8]. Some of the non-genetic factors are diet, age, body mass index (BMI), smoking, and alcohol consumption [2, 4,5,6]. It has been suggested that dietary components that have estrogen-mimicking properties and regulate the metabolism of endogenous estrogen may contribute to the development of UL [9]. Vegetarian diet, which is low in fat but rich in fibers, antioxidants, vitamins, phytochemicals, and minerals can protect against UL [8, 10,11,12,13,14].

Genetic predisposition plays a significant role in the onset and course of UL [15]. However, most genetic determinants of UL are still being explored. Consequently, the epidemiology of the disease has not been fully established [3, 16,17,18,19]. In-depth knowledge of the genetics of UL could help in identifying susceptible individuals [7, 18, 20, 21]. Hence, elucidating the molecular mechanisms behind UL development is important.

Genetic susceptibility to UL has been identified through genome-wide association studies (GWAS) that have uncovered DNA variations associated with the condition [20,21,22]. Single nucleotide polymorphisms (SNPs) are the most common type of gene variants in humans [19]. GWAS have identified BET1L rs2280543 as one of the most significant candidate SNPs for UL [21, 23]. The association of BET1L rs2280543 polymorphism with UF was initially reported among Japanese women [21] and later replicated in Han Chinese [24], European American [18, 23], and Japanese women [25]. However, both variables did not appear to be significantly related among Saudi [26] and black American women [27].

Due to conflicting reports regarding UL predisposing factors [4, 27, 28], it is crucial to evaluate the etiology of the disease [2, 18]. Moreover, replication of identified UL-associated SNPs within different populations is needed to validate the findings from GWAS [29]. To our knowledge, the association between BET1L rs2280543 and UL has not been determined among Taiwanese women. Therefore, we conducted this study to investigate the relationship between BET1L rs2280543 and UL among Taiwanese premenopausal women. Because UL has a multifactorial etiology, we further investigated whether BET1L rs2280543 and vegetarian diet could interact and influence the risk of UL.

Materials and methods

Data source

Using encrypted personal identification numbers, we linked the TWB, a repository containing genotypic, lifestyle, and biochemical data collected between 2008 and 2015 to the NHIRD which had information on diseases diagnosed between 1998 and 2015. All analyses were done at the Health and Welfare Data Science Center (HWDC) [30].

Variable definitions

In the NHIRD, we identified diseases based on either two outpatient visits or one-time admission using ICD-9 codes. The codes were 218.0, 218.1, 218.2, and 218.9 (for uterine fibroids), 401-405, A260, A269 (for hypertension), and 250, A181 (for diabetes mellitus). Vegetarians included those who maintained a vegetarian diet for at least six months prior to data collection. Participants who used western hormonal medications for more than half a year for gynecologic purposes like contraception, menopausal syndrome, and others were considered as hormone users. Herbal medicine users referred to those who used Chinese traditional medicine continuously for at least three months and were still using it during their recruitment into the Biobank project. Other variables such as physical activity, cigarette smoking, body mass index (BMI), alcohol, tea, and coffee consumption, have previously been described [31, 32]. We assessed and categorized fat intake based on twelve questions pertaining to the frequency of eating fat-containing foods over the previous month (Additional file 1: Table S1). The response scale ranged from 1 to 5 (i.e., 1 = never, 2 = seldom, 3 = sometimes, 4 = frequently, and 5 = always). We derived the fat intake scores (ranging from 12 to 60) for participants by calculating their responses to the 12 questions. The scores were grouped into quartiles: ≤ 35 (< Q1), 36–40 (Q1–Q2), 41–44 (Q2–Q3), and ≥ 45 (> Q3). The higher the score, the more likely the participants were inclined to low-fat foods.

BET1L rs2280543 was selected based on literature search and was genotyped using the custom Taiwan biobank chip (Axiom™ Genome-Wide Array Plate System (Affymetrix, Santa Clara, CA, USA). This SNP was included in the Taiwan Biobank because it met the quality control criteria: call rate > 95%, p value > 1.0 × 10–3 for the Hardy–Weinberg equilibrium test, and minor allele frequency > 0.05.

Exclusion criteria

Initially, we included 2578 premenopausal women in the study. However, we excluded those with incomplete questionnaires (n = 578) and genotype (n = 3). Complete data were available for 341 cases of uterine fibroid (test group) and 1656 controls. Signed informed consents were obtained from all participants. We obtained ethical approval from the Institutional Review Board of Chung Shan Medical University Hospital (CS2-20006).

Statistical analyses

All analyses were done using PLINK 1.09 and the statistical analysis system (SAS) software (version 9.4). We compared the differences between categorical and continuous variables using the Chi-square test and t-test, respectively. The test group comprised women with uterine fibroid, while the controls were those without uterine fibroid. Using logistic regression analysis, we estimated ORs for uterine fibroid with their 95% CI based on vegetarian status and rs2280543 genotypes. We also used logistic regression analysis to determine the interaction between vegetarian diet and BET1L rs2280543 on UF. Covariates included in the regression model were age, smoking, alcohol intake, exercise, hypertension, diabetes, hormone use, coffee and tea consumption, use of herbal medicine, family history of uterine fibroid, fat intake score, body mass index, parity, miscarriage, and or abortion.

Results

Baseline characteristics of the 1997 participants stratified by vegetarian status are displayed in Table 1. There were 49 vegetarians and 292 non-vegetarians with uterine fibroids. BET1L rs2280543 genotypes, smoking, alcohol intake, exercise, hypertension, diabetes, hormone use, miscarriage/abortion, body mass index, age at menarche, parity, and family history of uterine fibroids did not differ between the two groups. However, age, coffee consumption, and fat intake scores between vegetarians and non-vegetarians differed significantly (p < 0.05). The rs2280543 CC genotype was the wildtype, C was the major allele, while T was the minor allele with a minor allele frequency (MAF) of 0.128935. Compared to participants with the BET1L rs2280543 CC genotype, those with the CT/TT genotype had a lower OR for UL (0.69; 95% CI 0.51–0.93), indicating a lower risk of getting the disease (Table 2). Vegetarians compared to non-vegetarians had an OR of 1.09 (95% CI 0.77–1.55). Compared to participants aged 30–39 years, those in the 40–49 and 50–59 age groups had ORs of 3.05 (95% CI 2.20–4.21) and 4.51 (95% CI 2.96–6.87), respectively. For other variables significantly associated with UL, the ORs were 0.9 (95% CI 0.82–0.99) for age at menarche, 1.70 (95% CI 1.22–2.38) for use of herbal medicine, 1.84 (95% CI 1.38–2.45) for family history of uterine fibroid, and 1.45 (95% CI 1.12–1.89) for miscarriage and/or abortion. Compared to participants with a dietary habit score of 0–35, those with scores 45–60 had OR for uterine fibroid of 0.66 (95% CI 0.46–0.95). The test for interaction was significant for the BET1L rs2280543 genetic variant and vegetarian diet (p for interaction = 0.046). After stratification (Table 3), the ORs among vegetarians and non-vegetarians with CT/TT genotype compared to the CC genotype were 0.77 (95% CI 0.57–1.06) and 0.15 (95% CI 0.05–0.47), respectively. Older age remained a significant risk factor for uterine fibroid among vegetarians and non-vegetarians whereas age at menarche, herbal medicine use, family history of uterine fibroid, and miscarriage/abortion were significant risk factors only among non-vegetarians. Using rs2280543 CC and non-vegetarian diet as the reference group (Table 4), the OR for uterine fibroid was 1.32 (95% CI 0.90–1.94) among vegetarians with the CC genotype, 0.78 (95% CI 0.57–1.07) among non-vegetarians with the CT/TT genotype, and 0.37 (95% CI 0.15–0.91) among vegetarians with the CT/TT genotype.

Table 1 Baseline characteristics of participants by vegetarian status
Table 2 Odds of uterine fibroids among participants
Table 3 Risk of uterine fibroids stratified by vegetarian status
Table 4 Risk of uterine fibroids based on BET1L rs2280543 genotypes and vegetarian status

Discussion

BET1L rs2280543 CT + TT genotype was significantly associated with a lower risk of UL among premenopausal Taiwanese vegetarians. Our results support previous findings on the involvement of BET1L rs2280543 polymorphism in UF pathogenesis [21]. So far, this is the first study to replicate the association between BET1L rs2280543 and UL among Taiwanese women. It is also the first study to demonstrate a significant interaction between BET1L rs2280543 and vegetarian diet on the risk of UF.

In addition to the identification of susceptible individuals [7, 18, 20, 21], insights into the molecular aspects of UL could assist in the development of targeted therapies. Several clinical management options for ULs are available and some are under investigation [33, 34]. Current treatment options for UL could be improved by incorporating the molecular information on UL. This might optimize treatment outcomes.

Profound knowledge of the lifestyle factors associated with UL could uncover non-invasive preventive and management options that could reduce UL-related surgical procedures and costs [2]. There is controversy regarding the impact of diet on UL risk [2, 9]. Notwithstanding, several studies have reported significant inverse associations between vegetarian diet and UL risk [8, 10,11,12,13,14]. The protective effect of vegetarian diet against UL is, in part accounted for by high fiber contents [10]. A low-fat and high-fiber diet (such as a vegetarian diet) affects the metabolism and activities of sex hormones and is believed to enhance fecal excretion of estrogen [35, 36]. Additionally, phytoestrogens (plant-derived estrogens) could reduce the risk of UL because they are believed to compete for estrogen receptors with estradiol [12]. Moreover, phytochemicals and antioxidants in vegetarian diet could enhance apoptosis [26, 37, 38] and inhibit estrogen metabolism [12, 37, 38]. It should be noted that estrogen levels are directly associated with the risk of UL [28, 39,40,41,42].

The biological role of BET1L rs2280543 predisposition to UL has been proven by its significant link with BET1L transcription and expression [21, 24]. Similar to our findings, BET1L rs2280543 was significantly associated with a lower risk of UL among Han Chinese [24] and European Americans [18, 23]. Although this SNP was first reported [21] and later replicated among Japanese [25], their findings differed from ours and other findings [18, 23, 24]. This could be due to discrepancies in the reference allele/genotype in the various studies. For instance, Sakai and colleagues used T as their reference allele while we and other authors used CC as the reference genotype. The association of BET1L rs2280543 and UL risk was not significant among black Americans [27] and Saudi women [26].

Delayed menarche was associated with a lower risk, while increasing age was associated with a higher risk of UL in our study, confirming previously published findings [5, 6, 27, 28, 42,43,44,45]. Other significant risk factors that we observed include, BMI, use of herbal medicine, family history, miscarriage, and abortion. These factors have also been previously reported [2, 45,46,47,48,49,50,51,52,53].

Consumption of vegetarian food rich in fats, such as oil-cooked vegetables could negate the health benefits of a vegetarian diet [54]. As such, we adjusted for this using the fat intake score and found that those who consumed foods relatively low in fat had a lower risk of UL. Therefore, in studies focusing on vegetarian diet, consideration of cooking methods and fat intake habits could help minimize errors in estimating the health benefits of vegetarian diet.

Strengths and limitations

The large sample size is the strength of our study. However, since participation in the Taiwan Biobank project is restricted to individuals aged 30–70 years, we could not determine the association in premenopausal women aged below 30 years. As such, our results may not be generalized to all Taiwanese premenopausal women.

Conclusions

In this study, BET1L rs2280543 CT + TT was associated with a lower risk of uterine fibroids, especially among vegetarians. These findings add to existing knowledge on the interplay between genetic and lifestyle factors in the development of UL, shedding more light on the epidemiology of the disease. From our findings, a vegetarian diet could prevent or reduce the risk of UL and, therefore, should be recommended.

Availability of data and materials

The data that support the findings of this study are available from Taiwan Biobank but restrictions apply to the availability of these data, which were used under license for the current study, and so are not publicly available. Data are however available from the authors upon reasonable request and with permission of Taiwan Biobank.

References

  1. Nivethithai P, Nikhat S, Rajesh B. Uterine fibroids: a review. Indian Journal of Pharmacy Practice. 2010;3(1).

  2. Sparic R, Mirkovic L, Malvasi A, Tinelli A. Epidemiology of uterine myomas: a review. Int J Fertil Steril. 2016;9(4):424.

    PubMed  Google Scholar 

  3. Segars JH, Parrott EC, Nagel JD, Guo XC, Gao X, Birnbaum LS, et al. Proceedings from the Third National Institutes of Health International Congress on Advances in Uterine Leiomyoma Research: comprehensive review, conference summary and future recommendations. Hum Reprod Update. 2014;20(3):309–33.

    Article  PubMed  PubMed Central  Google Scholar 

  4. Wise LA, Laughlin-Tommaso SK. Uterine leiomyomata. Women and health. Elsevier Inc.; 2013. p. 285–305.

    Book  Google Scholar 

  5. Othman E-ER, Al-Hendy A. Molecular genetics and racial disparities of uterine leiomyomas. Best Pract Res Clin Obstet Gynaecol. 2008;22(4):589–601.

    Article  PubMed  PubMed Central  Google Scholar 

  6. Parker WH. Etiology, symptomatology, and diagnosis of uterine myomas. Fertil Steril. 2007;87(4):725–36.

    Article  PubMed  Google Scholar 

  7. Medikare V, Kandukuri LR, Ananthapur V, Deenadayal M, Nallari P. The genetic bases of uterine fibroids; a review. J Reprod Infertil. 2011;12(3):181.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Wise LA, Radin RG, Palmer JR, Kumanyika SK, Boggs DA, Rosenberg L. Intake of fruit, vegetables, and carotenoids in relation to risk of uterine leiomyomata. Am J Clin Nutr. 2011;94(6):1620–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Parazzini F, Di Martino M, Candiani M, Viganò P. Dietary components and uterine leiomyomas: a review of published data. Nutr Cancer. 2015;67(4):569–79.

    Article  CAS  PubMed  Google Scholar 

  10. He Y, Zeng Q, Dong S, Qin L, Li G, Wang P. Associations between uterine fibroids and lifestyles including diet, physical activity and stress: a case-control study in China. Asia Pac J Clin Nutr. 2013;22(1):109.

    PubMed  Google Scholar 

  11. Chiaffarino F, Parazzini F, La Vecchia C, Chatenoud L, Di Cintio E, Marsico S. Diet and uterine myomas. Obstet Gynecol. 1999;94(3):395–8.

    CAS  PubMed  Google Scholar 

  12. Shen Y, Wu Y, Lu Q, Ren M. Vegetarian diet and reduced uterine fibroids risk: a case–control study in Nanjing, China. J Obstet Gynaecol Res. 2016;42(1):87–94.

    Article  PubMed  Google Scholar 

  13. Heber D, Bowerman S. Applying science to changing dietary patterns. J Nutr. 2001;131(11):3078S-S3081.

    Article  CAS  PubMed  Google Scholar 

  14. Slavin JL, Lloyd B. Health benefits of fruits and vegetables. Adv Nutr. 2012;3(4):506–16.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Svirepova KA, Mv K, Ns S, Dv Z, Ea L, Gv M, et al. Hereditary risk factors for uterine leiomyoma: a search for marker SNPS. Bulletin of Russian State Medical University. 2020(1).

  16. Yang Q, Mas A, Diamond MP, Al-Hendy A. The mechanism and function of epigenetics in uterine leiomyoma development. Reprod Sci. 2016;23(2):163–75.

    Article  CAS  PubMed  Google Scholar 

  17. Pavone D, Clemenza S, Sorbi F, Fambrini M, Petraglia F. Epidemiology and risk factors of uterine fibroids. Best Pract Res Clin Obstet Gynaecol. 2018;46:3–11.

    Article  PubMed  Google Scholar 

  18. Edwards TL, Michels KA, Hartmann KE, Edwards DRV. BET1L and TNRC6B associate with uterine fibroid risk among European Americans. Hum Genet. 2013;132(8):943–53.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Ramírez-Bello J, Jiménez-Morales M. Functional implications of single nucleotide polymorphisms (SNPs) in protein-coding and non-coding RNA genes in multifactorial diseases. Gac Med Mex. 2017;153(2):238–50.

    PubMed  Google Scholar 

  20. Välimäki N, Kuisma H, Pasanen A, Heikinheimo O, Sjöberg J, Bützow R, et al. Genetic predisposition to uterine leiomyoma is determined by loci for genitourinary development and genome stability. Elife. 2018;7: e37110.

    Article  PubMed  PubMed Central  Google Scholar 

  21. Cha P-C, Takahashi A, Hosono N, Low S-K, Kamatani N, Kubo M, et al. A genome-wide association study identifies three loci associated with susceptibility to uterine fibroids. Nat Genet. 2011;43(5):447–50.

    Article  CAS  PubMed  Google Scholar 

  22. Gallagher C, Mäkinen N, Harris H, Rahmioglu N, Uimari O, Cook J, et al. Genome-wide association and epidemiological analyses reveal common genetic origins between uterine leiomyomata and endometriosis. Nat Commun. 2019;10(1):1–11.

    Article  CAS  Google Scholar 

  23. Edwards TL, Hartmann KE, Edwards DRV. Variants in BET1L and TNRC6B associate with increasing fibroid volume and fibroid type among European Americans. Hum Genet. 2013;132(12):1361–9.

    Article  CAS  PubMed  Google Scholar 

  24. Liu B, Wang T, Jiang J, Li M, Ma W, Wu H, et al. Association of BET1L and TNRC6B with uterine leiomyoma risk and its relevant clinical features in Han Chinese population. Sci Rep. 2018;8(1):1–6.

    Google Scholar 

  25. Sakai K, Tanikawa C, Hirasawa A, Chiyoda T, Yamagami W, Kataoka F, et al. Identification of a novel uterine leiomyoma GWAS locus in a Japanese population. Sci Rep. 2020;10(1):1–8.

    Article  CAS  Google Scholar 

  26. Bondagji NS, Morad FA, Al-Nefaei AAA, Khan IA, Elango R, Abdullah LS, et al. Replication of GWAS loci revealed the moderate effect of TNRC6B locus on susceptibility of Saudi women to develop uterine leiomyomas. J Obstet Gynaecol Res. 2017;43(2):330–8.

    Article  CAS  PubMed  Google Scholar 

  27. Wise LA, Ruiz-Narvaez EA, Palmer JR, Cozier YC, Tandon A, Patterson N, et al. African ancestry and genetic risk for uterine leiomyomata. Am J Epidemiol. 2012;176(12):1159–68.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Wise LA, Palmer JR, Harlow BL, Spiegelman D, Stewart EA, Adams-Campbell LL, et al. Reproductive factors, hormonal contraception, and risk of uterine leiomyomata in African-American women: a prospective study. Am J Epidemiol. 2004;159(2):113–23.

    Article  PubMed  Google Scholar 

  29. Aissani B, Zhang K, Wiener H. Evaluation of GWAS candidate susceptibility loci for uterine leiomyoma in the multi-ethnic NIEHS uterine fibroid study. Front Genet. 2015;6:241.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  30. Hsieh C-Y, Su C-C, Shao S-C, Sung S-F, Lin S-J, Yang Y-HK, et al. Taiwan’s national health insurance research database: past and future. Clin Epidemiol. 2019;11:349.

    Article  PubMed  PubMed Central  Google Scholar 

  31. Tantoh DM, Lee K-J, Nfor ON, Liaw Y-C, Lin C, Chu H-W, et al. Methylation at cg05575921 of a smoking-related gene (AHRR) in non-smoking Taiwanese adults residing in areas with different PM 2.5 concentrations. Clin Epigenetics. 2019;11(1):69.

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  32. Nfor ON, Wu M-F, Lee C-T, Wang L, Liu W-H, Tantoh DM, et al. Body mass index modulates the association between CDKAL1 rs10946398 variant and type 2 diabetes among Taiwanese women. Sci Rep. 2018;8(1):1–7.

    Article  CAS  Google Scholar 

  33. Angioni S, D’Alterio MN, Daniilidis A. Highlights on medical treatment of uterine fibroids. Curr Pharm Des. 2021;27:3821–32.

    Article  CAS  PubMed  Google Scholar 

  34. Dababou S, Garzon S, Laganà AS, Ferrero S, Evangelisti G, Noventa M, et al. Linzagolix: a new GnRH-antagonist under investigation for the treatment of endometriosis and uterine myomas. Expert Opin Investig Drugs. 2021;30(9):903–11.

    Article  CAS  PubMed  Google Scholar 

  35. Aubertin-Leheudre M, Gorbach S, Woods M, Dwyer JT, Goldin B, Adlercreutz H. Fat/fiber intakes and sex hormones in healthy premenopausal women in USA. J Steroid Biochem Mol Biol. 2008;112(1–3):32–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Barnard ND, Scialli AR, Hurlock D, Bertron P. Diet and sex-hormone binding globulin, dysmenorrhea, and premenstrual symptoms. Obstet Gynecol. 2000;95(2):245–50.

    CAS  PubMed  Google Scholar 

  37. Potter JD, Steinmetz K. Vegetables, fruit and phytoestrogens as preventive agents. IARC Sci Publ. 1996;139:61–90.

    CAS  Google Scholar 

  38. Adlercreutz H, Mazur W. Phyto-oestrogens and Western diseases. Ann Med. 1997;29(2):95–120.

    Article  CAS  PubMed  Google Scholar 

  39. Hunter DS, Hodges LC, Eagon PK, Vonier PM, Fuchs-Young R, Bergerson JS, et al. Influence of exogenous estrogen receptor ligands on uterine leiomyoma: evidence from an in vitro/in vivo animal model for uterine fibroids. Environ Health Perspect. 2000;108 Suppl 5:829–34.

    Article  CAS  PubMed  Google Scholar 

  40. Borahay MA, Asoglu MR, Mas A, Adam S, Kilic GS, Al-Hendy A. Estrogen receptors and signaling in fibroids: role in pathobiology and therapeutic implications. Reprod Sci. 2017;24(9):1235–44.

    Article  CAS  PubMed  Google Scholar 

  41. Maruo T, Ohara N, Wang J, Matsuo H. Sex steroidal regulation of uterine leiomyoma growth and apoptosis. Hum Reprod Update. 2004;10(3):207–20.

    Article  CAS  PubMed  Google Scholar 

  42. Flake GP, Andersen J, Dixon D. Etiology and pathogenesis of uterine leiomyomas: a review. Environ Health Perspect. 2003;111(8):1037–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Sato F, Miyake H, Nishi M, Mori M, Kudo R. Early normal menstrual cycle pattern and the development of uterine leiomyomas. J Womens Health Gend Based Med. 2000;9(3):299–302.

    Article  CAS  PubMed  Google Scholar 

  44. Wise LA, Laughlin-Tommaso SK. Epidemiology of uterine fibroids–from menarche to menopause. Clin Obstet Gynecol. 2016;59(1):2.

    Article  PubMed  PubMed Central  Google Scholar 

  45. Stewart EA, Cookson C, Gandolfo RA, Schulze-Rath R. Epidemiology of uterine fibroids: a systematic review. BJOG Int J Obstet Gynaecol. 2017;124(10):1501–12.

    Article  CAS  Google Scholar 

  46. Hsu W-C, Tsai Y-T, Hou Y-C, Lai J-N. Prescription of Chinese herbal products is associated with a decreased risk of uterine fibroids: a population-based cohort study. Medicine. 2019;98(51): e18195.

    Article  PubMed  PubMed Central  Google Scholar 

  47. Su S-Y, Muo C-H, Morisky DE. Use of Chinese medicine and subsequent surgery in women with uterine fibroid: a retrospective cohort study. Evid Based Complement Alternat Med. 2012;2012: 617918.

    Article  PubMed  PubMed Central  Google Scholar 

  48. Song L, Shen L, Mandiwa C, Yang S, Liang Y, Yuan J, et al. Induced and spontaneous abortion and risk of uterine fibroids. J Womens Health. 2017;26(1):76–82.

    Article  Google Scholar 

  49. Lumbiganon P, Rugpao S, Phandhu-fung S, Laopaiboon M, Vudhikamraksa N, Werawatakul Y. Protective effect of depot-medroxyprogesterone acetate on surgically treated uterine leiomyomas: a multicentre case-control study. BJOG Int J Obstet Gynaecol. 1996;103(9):909–14.

    Article  CAS  Google Scholar 

  50. Sato F, Mori M, Nishi M, Kudo R, Miyake H. Familial aggregation of uterine myomas in Japanese women. J Epidemiol. 2002;12(3):249–53.

    Article  PubMed  Google Scholar 

  51. Shen Y, Xu Q, Xu J, Ren M, Cai Y. Environmental exposure and risk of uterine leiomyoma: an epidemiologic survey. Eur Rev Med Pharmacol Sci. 2013;17(23):3249–56.

    CAS  PubMed  Google Scholar 

  52. Ciebiera M, Włodarczyk M, Słabuszewska-Jóźwiak A, Nowicka G, Jakiel G. Influence of vitamin D and transforming growth factor β3 serum concentrations, obesity, and family history on the risk for uterine fibroids. Fertil Steril. 2016;106(7):1787–92.

    Article  CAS  PubMed  Google Scholar 

  53. Ciebiera M, Wrzosek M, Wojtyła C, Łoziński T, Nowicka G, Jakiel G, et al. Oestrogen receptor alpha PvuII polymorphism and uterine fibroid incidence in Caucasian women. Prz Menopauzalny. 2018;17(4):149.

    CAS  PubMed  PubMed Central  Google Scholar 

  54. Wu J-H, Chang Y-K, Hou Y-C, Chiu W-J, Chen J-R, Chen S-T, et al. Meat-fat dietary pattern may increase the risk of breast cancer—a case–control study in Taiwan. Tzu Chi Medical Journal. 2013;25(4):233–8.

    Article  Google Scholar 

Download references

Acknowledgements

We appreciate the Ministry of Science and Technology (MOST), Taiwan and the Chung Shan Medical University Hospital for partially funding this work.

Funding

Funding for this work was provided by the Ministry of Science and Technology, MOST (MOST 108-2621-M-040-001and 109-2121-M-040-002) and Chung Shan Medical University Hospital (CSH-2020-C-023 and CSH-2020-C-010).

Author information

Authors and Affiliations

Authors

Contributions

Conceptualization, SCL, YHC, DMT, SYH, ONN, YST, and YPL; Formal analysis, SYH and YPL; Methodology, SCL, YHC, DMT, SYH, ONN, YST, and YPL; Supervision, YPL; Validation, SCL, YHC, DMT, SYH, ONN, YST, and YPL; Writing—original SCL and DMT; Writing—review & editing, SCL, YHC, DMT, SYH, ONN, YST, and YPL. All authors have read and approved the manuscript.

Corresponding author

Correspondence to Yung-Po Liaw.

Ethics declarations

Ethics approval and consent to participate

All methods were performed in accordance with the relevant guidelines and regulations (Declaration of Helsinki). Signed informed consents were obtained from all participants. The Chung Shan Medical University Institutional Review Board (CS2-20006) granted ethical approval for this study.

Consent for publication

Not applicable.

Competing interests

The authors declare that they have no competing interests.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Supplementary Information

Additional file 1: Table S1.

Questions pertaining to the frequency of eating fat-containing foods over the previous month.

Rights and permissions

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Lee, S.C., Chou, YH., Tantoh, D.M. et al. Risk of uterine leiomyoma based on BET1L rs2280543 single nucleotide polymorphism and vegetarian diet. BMC Women's Health 22, 139 (2022). https://doi.org/10.1186/s12905-022-01721-1

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1186/s12905-022-01721-1

Keywords