Top

Published in:

01-12-2021 | Lung Cancer | Research article

Associations between female lung cancer risk and sex steroid hormones: a systematic review and meta-analysis of the worldwide epidemiological evidence on endogenous and exogenous sex steroid hormones

Authors: Hui Zeng, Zhuoyu Yang, Jiang Li, Yan Wen, Zheng Wu, Yadi Zheng, Yiwen Yu, Yongjie Xu, Shugeng Gao, Fengwei Tan, Ni Li, Qi Xue, Jie He

Published in: BMC Cancer | Issue 1/2021

Abstract

Background

Published findings suggest sex differences in lung cancer risk and a potential role for sex steroid hormones. Our aim was to perform a meta-analysis to investigate the effects of sex steroid hormone exposure specifically on the risk of lung cancer in women.

Methods

The PubMed, MEDLINE, Web of Science, and EMBASE databases were searched. The pooled odds ratios (ORs) and 95% confidence intervals (95% CIs) for female lung cancer risk associated with sex steroid hormones were calculated overall and by study design, publication year, population, and smoking status. Sensitivity analysis, publication bias, and subgroup analysis were performed.

Results

Forty-eight studies published between 1987 and 2019 were included in the study with a total of 31,592 female lung cancer cases and 1,416,320 subjects without lung cancer. Overall, higher levels of sex steroid hormones, both endogenous (OR: 0.92, 95% CI: 0.87–0.98) and exogenous (OR: 0.86, 95% CI: 0.80–0.93), significantly decreased the risk of female lung cancer by 10% (OR: 0.90, 95% CI: 0.86–0.95). The risk of lung cancer decreased more significantly with a higher level of sex steroid hormones in non-smoking women (OR: 0.88, 95% CI: 0.78–0.99) than in smoking women (OR: 0.98, 95% CI: 0.77–1.03), especially in Asia women (OR: 0.84, 95% CI: 0.74–0.96).

Conclusions

Our meta-analysis reveals an association between higher levels of sex steroid hormone exposure and the decreased risk of female lung cancer. Surveillance of sex steroid hormones might be used for identifying populations at high risk for lung cancer, especially among non-smoking women.

Available only for authorised users

Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J, Jemal A. Global cancer statistics, 2012. CA Cancer J Clin. 2015;65(2):87–108. https://doi.org/10.3322/caac.21262.CrossRefPubMed

Siegel RL, Miller KD, Jemal A. Cancer statistics, 2020. CA Cancer J Clin. 2020;70(1):7–30. https://doi.org/10.3322/caac.21590.CrossRefPubMed

Chien LH, Chen CH, Chen TY, Chang GC, Tsai YH, Hsiao CF, et al. Predicting Lung Cancer Occurrence in Never-Smoking Females in Asia: TNSF-SQ, a Prediction Model. Cancer Epidemiol Biomarkers Prevention. 2020;29(2):452–9.

Sun S, Schiller JH, Gazdar AF. Lung cancer in never smokers — a different disease. Nat Rev Cancer. 2007;7(10):778–90. https://doi.org/10.1038/nrc2190.CrossRefPubMed

Ferlay J, Shin HR, Bray F, Forman D, Mathers C, Parkin DM. Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer. 2010;127(12):2893–917. https://doi.org/10.1002/ijc.25516.CrossRefPubMed

Bae JM. Modifiable risk factors of lung cancer in “never-smoker” women. Epidemiol Health. 2015;37:e2015047. https://doi.org/10.4178/epih/e2015047.CrossRefPubMedPubMedCentral

Bravo-Iniguez CE, Fox SW, De Leon LE, Tarascio JN, Jaklitsch MT, Jacobson FL. Cumulative nonsmoking risk factors increase the probability of developing lung cancer. J Thorac Cardiovasc Surg. 2019;158(4):1248–1254.e1.CrossRefPubMed

Wakelee HA, Chang ET, Gomez SL, Keegan TH, Feskanich D, Clarke CA, et al. Lung cancer incidence in never smokers. J Clin Oncol. 2007;25(5):472–8. https://doi.org/10.1200/JCO.2006.07.2983.CrossRefPubMed

Yano T, Miura N, Takenaka T, Haro A, Okazaki H, Ohba T, et al. Never-smoking nonsmall cell lung cancer as a separate entity: clinicopathologic features and survival. Cancer. 2008;113(5):1012–8. https://doi.org/10.1002/cncr.23679.CrossRefPubMed

10.

Bade BC, Dela Cruz CS. Lung cancer 2020: epidemiology, etiology, and prevention. Clin Chest Med. 2020;41(1):1–24. https://doi.org/10.1016/j.ccm.2019.10.001.CrossRefPubMed

11.

Siddiqui F, Bae K, Langer CJ, Coyne JC, Gamerman V, Komaki R, et al. The influence of gender, race, and marital status on survival in lung cancer patients: analysis of radiation therapy oncology group trials. J Thorac Oncol. 2010;5(5):631–9. https://doi.org/10.1097/JTO.0b013e3181d5e46a.CrossRefPubMed

12.

Ou SH, Zell JA, Ziogas A, Anton-Culver H. Prognostic factors for survival of stage I nonsmall cell lung cancer patients : a population-based analysis of 19,702 stage I patients in the California Cancer registry from 1989 to 2003. Cancer. 2007;110(7):1532–41. https://doi.org/10.1002/cncr.22938.CrossRefPubMed

13.

Kawaguchi T, Takada M, Kubo A, Matsumura A, Fukai S, Tamura A, et al. Performance status and smoking status are independent favorable prognostic factors for survival in non-small cell lung cancer: a comprehensive analysis of 26,957 patients with NSCLC. J Thorac Oncol. 2010;5(5):620–30. https://doi.org/10.1097/JTO.0b013e3181d2dcd9.CrossRefPubMed

14.

Henschke CI, Yip R, Miettinen OS. Women's susceptibility to tobacco carcinogens and survival after diagnosis of lung cancer. Jama. 2006;296(2):180–4. https://doi.org/10.1001/jama.296.2.180.CrossRefPubMed

15.

Corrales L, Rosell R, Cardona AF, Martin C, Zatarain-Barron ZL, Arrieta O. Lung cancer in never smokers: the role of different risk factors other than tobacco smoking. Crit Rev Oncol Hematol. 2020;148:102895. https://doi.org/10.1016/j.critrevonc.2020.102895.CrossRefPubMed

16.

Cheng TD, Darke AK, Redman MW, Zirpoli GR, Davis W, Payne Ondracek R, et al. Smoking, sex, and non-small cell lung cancer: steroid hormone receptors in tumor tissue (S0424). J Natl Cancer Inst. 2018;110(7):734–42. https://doi.org/10.1093/jnci/djx260.CrossRefPubMedPubMedCentral

17.

Gao YT, Blot WJ, Zheng W, Ershow AG, Hsu CW, Levin LI, et al. Lung cancer among Chinese women. Int J Cancer. 1987;40(5):604–9. https://doi.org/10.1002/ijc.2910400505.CrossRefPubMed

18.

Jin C, Lang B. Hormone replacement therapy and lung cancer risk in women: a meta-analysis of cohort studies: hormone replacement therapy and lung cancer risk. Medicine. 2019;98(51):e17532. https://doi.org/10.1097/MD.0000000000017532.CrossRefPubMedPubMedCentral

19.

Min L, Wang F, Liang S, Yang J, Xu X. Menopausal status and the risk of lung cancer in women: a PRISMA-compliant meta-analysis. Medicine. 2017;96(26):e7065. https://doi.org/10.1097/MD.0000000000007065.CrossRefPubMedPubMedCentral

20.

Weiss JM, Lacey JV Jr, Shu XO, Ji BT, Hou L, Yang G, et al. Menstrual and reproductive factors in association with lung cancer in female lifetime nonsmokers. Am J Epidemiol. 2008;168(11):1319–25. https://doi.org/10.1093/aje/kwn257.CrossRefPubMedPubMedCentral

21.

Oh SW, Myung SK, Park JY, Lym YL, Ju W. Hormone therapy and risk of lung cancer: a meta-analysis. J Women's Health (2002). 2010;19(2):279–88.CrossRef

22.

Zhang Y, Yin Z, Shen L, Wan Y, Zhou B. Menstrual factors, reproductive factors and lung cancer risk: a meta-analysis. Zhongguo Fei Ai Za Zhi. 2012;15(12):701–19. https://doi.org/10.3779/j.issn.1009-3419.2012.12.04.CrossRefPubMedPubMedCentral

23.

Honma N, Hosoi T, Arai T, Takubo K. Estrogen and cancers of the colorectum, breast, and lung in postmenopausal women. Pathol Int. 2015;65(9):451–9. https://doi.org/10.1111/pin.12326.CrossRefPubMed

24.

Bae JM, Kim EH. Hormonal replacement therapy and the risk of lung cancer in women: an adaptive meta-analysis of cohort studies. J Prev Med Public Health. 2015;48(6):280–6.CrossRefPubMedPubMedCentral

25.

Pesatori AC, Carugno M, Consonni D, Hung RJ, Papadoupolos A, Landi MT, et al. Hormone use and risk for lung cancer: a pooled analysis from the international lung cancer consortium (ILCCO). Br J Cancer. 2013;109(7):1954–64. https://doi.org/10.1038/bjc.2013.506.CrossRefPubMedPubMedCentral

26.

Yao Y, Gu X, Zhu J, Yuan D, Song Y. Hormone replacement therapy in females can decrease the risk of lung cancer: a meta-analysis. PLoS One. 2013;8(8):e71236. https://doi.org/10.1371/journal.pone.0071236.CrossRefPubMedPubMedCentral

27.

Dahabreh IJ, Trikalinos TA, Paulus JK. Parity and risk of lung cancer in women: systematic review and meta-analysis of epidemiological studies. Lung Cancer (Amsterdam, Netherlands). 2012;76(2):150–8.CrossRef

28.

Wu W, Yin ZH, Guan P, Ren YW, Zhou BS. Association of oral contraceptives use and lung cancer risk among women: an updated meta-analysis based on cohort and case-control studies. Asian Pac J Cancer Prev. 2014;15(3):1205–10. https://doi.org/10.7314/APJCP.2014.15.3.1205.CrossRefPubMed

29.

Zeng H. Supplementary_Material.pdf. figshare. Dataset; 2020. https://doi.org/10.6084/m9.figshare.12991559.v2.CrossRef

30.

Hutton B, Salanti G, Caldwell DM, Chaimani A, Schmid CH, Cameron C, et al. The PRISMA extension statement for reporting of systematic reviews incorporating network meta-analyses of health care interventions: checklist and explanations. Ann Intern Med. 2015;162(11):777–84. https://doi.org/10.7326/M14-2385.CrossRefPubMed

31.

Mantel N, Haenszel W. Statistical aspects of the analysis of data from retrospective studies of disease. J Natl Cancer Inst. 1959;22(4):719–48.PubMed

32.

DerSimonian R, Kacker R. Random-effects model for meta-analysis of clinical trials: an update. Contemp Clin Trials. 2007;28(2):105–14. https://doi.org/10.1016/j.cct.2006.04.004.CrossRefPubMed

33.

Jin K, Wu M, Zhou JY, Yang J, Han RQ, Jin ZY, et al. Tobacco smoking modifies the association between hormonal factors and lung cancer occurrence among post-menopausal Chinese women. Transl Oncol. 2019;12(6):819–27. https://doi.org/10.1016/j.tranon.2019.03.001.CrossRefPubMedPubMedCentral

34.

Lim WY, Chen Y, Chuah KL, Eng P, Leong SS, Lim E, et al. Female reproductive factors, gene polymorphisms in the estrogen metabolism pathway, and risk of lung cancer in Chinese women. Am J Epidemiol. 2012;175(6):492–503. https://doi.org/10.1093/aje/kwr332.CrossRefPubMed

35.

Meinhold CL, Berrington de Gonzalez A, Bowman ED, Brenner AV, Jones RT, Lacey JV Jr, et al. Reproductive and hormonal factors and the risk of nonsmall cell lung cancer. Int J Cancer. 2011;128(6):1404–13. https://doi.org/10.1002/ijc.25434.CrossRefPubMedPubMedCentral

36.

Seow A, Poh WT, Teh M, Eng P, Wang YT, Tan WC, et al. Diet, reproductive factors and lung cancer risk among Chinese women in Singapore: evidence for a protective effect of soy in nonsmokers. Int J Cancer. 2002;97(3):365–71. https://doi.org/10.1002/ijc.1615.CrossRefPubMed

37.

Brinton LA, Gierach GL, Andaya A, Park Y, Schatzkin A, Hollenbeck AR, et al. Reproductive and hormonal factors and lung cancer risk in the NIH-AARP diet and health study cohort. Cancer Epidemiol Biomarkers Prev. 2011;20(5):900–11. https://doi.org/10.1158/1055-9965.EPI-10-1325.CrossRefPubMedPubMedCentral

38.

Paulus JK, Asomaning K, Kraft P, Johnson BE, Lin X, Christiani DC. Parity and risk of lung cancer in women. Am J Epidemiol. 2010;171(5):557–63. https://doi.org/10.1093/aje/kwp441.CrossRefPubMedPubMedCentral

39.

Rodriguez C, Spencer Feigelson H, Deka A, Patel AV, Jacobs EJ, Thun MJ, et al. Postmenopausal hormone therapy and lung cancer risk in the cancer prevention study II nutrition cohort. Cancer Epidemiol Biomarkers Prev. 2008;17(3):655–60. https://doi.org/10.1158/1055-9965.EPI-07-2683.CrossRefPubMed

40.

Schabath MB, Wu X, Vassilopoulou-Sellin R, Vaporciyan AA, Spitz MR. Hormone replacement therapy and lung cancer risk: a case-control analysis. Clin Cancer Res. 2004;10(1 Pt 1):113–23. https://doi.org/10.1158/1078-0432.CCR-0911-3.CrossRefPubMed

41.

Schabath MB, Hernandez LM, Wu X, Pillow PC, Spitz MR. Dietary phytoestrogens and lung cancer risk. Jama. 2005;294(12):1493–504. https://doi.org/10.1001/jama.294.12.1493.CrossRefPubMed

42.

Shimazu T, Inoue M, Sasazuki S, Iwasaki M, Sawada N, Yamaji T, et al. Isoflavone intake and risk of lung cancer: a prospective cohort study in Japan. Am J Clin Nutr. 2010;91(3):722–8. https://doi.org/10.3945/ajcn.2009.28161.CrossRefPubMed

43.

Arroyo P, Ho BS, Sau L, Kelley ST, Thackray VG. Letrozole treatment of pubertal female mice results in activational effects on reproduction, metabolism and the gut microbiome. PLoS One. 2019;14(9):e0223274. https://doi.org/10.1371/journal.pone.0223274.CrossRefPubMedPubMedCentral

44.

Patrone C, Cassel TN, Pettersson K, Piao YS, Cheng G, Ciana P, et al. Regulation of postnatal lung development and homeostasis by estrogen receptor beta. Mol Cell Biol. 2003;23(23):8542–52. https://doi.org/10.1128/MCB.23.23.8542-8552.2003.CrossRefPubMedPubMedCentral

45.

Murugappan G, Li S, Lathi RB, Baker VL, Eisenberg ML. Risk of cancer in infertile women: analysis of US claims data. Hum Reprod (Oxford, England). 2019;34(5):894–902.CrossRef

46.

Siegfried JM, Stabile LP. Estrongenic steroid hormones in lung cancer. Semin Oncol. 2014;41(1):5–16. https://doi.org/10.1053/j.seminoncol.2013.12.009.CrossRefPubMed

47.

Slowikowski BK, Lianeri M, Jagodzinski PP. Exploring estrogenic activity in lung cancer. Mol Biol Rep. 2017;44(1):35–50. https://doi.org/10.1007/s11033-016-4086-8.CrossRefPubMed

48.

Kadota K, Eguchi T, Villena-Vargas J, Woo KM, Sima CS, Jones DR, et al. Nuclear estrogen receptor-alpha expression is an independent predictor of recurrence in male patients with pT1aN0 lung adenocarcinomas, and correlates with regulatory T-cell infiltration. Oncotarget. 2015;6(29):27505–18. https://doi.org/10.18632/oncotarget.4752.CrossRefPubMedPubMedCentral

49.

Grivennikov SI, Greten FR, Karin M. Immunity, inflammation, and cancer. Cell. 2010;140(6):883–99. https://doi.org/10.1016/j.cell.2010.01.025.CrossRefPubMedPubMedCentral

50.

Chu K, Song Y, Chatooah ND, Weng Q, Ying Q, Ma L, et al. The use and discontinuation of hormone replacement therapy in women in South China. Climacteric. 2018;21(1):47–52. https://doi.org/10.1080/13697137.2017.1397622.CrossRefPubMed

51.

Peng J, Xu X, Mace BE, Vanderveer LA, Workman LR, Slifker MJ, et al. Estrogen metabolism within the lung and its modulation by tobacco smoke. Carcinogenesis. 2013;34(4):909–15. https://doi.org/10.1093/carcin/bgs402.CrossRefPubMed

52.

Liu S, Zhang M, Yang L, Li Y, Wang L, Huang Z, et al. Prevalence and patterns of tobacco smoking among Chinese adult men and women: findings of the 2010 national smoking survey. J Epidemiol Community Health. 2017;71(2):154–61. https://doi.org/10.1136/jech-2016-207805.CrossRefPubMed

Title: Associations between female lung cancer risk and sex steroid hormones: a systematic review and meta-analysis of the worldwide epidemiological evidence on endogenous and exogenous sex steroid hormones
Authors: Hui Zeng
Zhuoyu Yang
Jiang Li
Yan Wen
Zheng Wu
Yadi Zheng
Yiwen Yu
Yongjie Xu
Shugeng Gao
Fengwei Tan
Ni Li
Qi Xue
Jie He
Publication date: 01-12-2021
Publisher: BioMed Central
Keywords: Lung Cancer
Lung Cancer
Oral Contraception
Lung Cancer
Published in: BMC Cancer / Issue 1/2021
Electronic ISSN: 1471-2407
DOI: https://doi.org/10.1186/s12885-021-08437-9

2024 ASCO Annual Meeting Coverage

Highlights of the Day: Breast cancer – metastatic

Breast Cancer Video

In this session, Dr. Wolff provides his key takeaways from the data presented in the metastatic breast cancer oral abstract session at ASCO 2024.

Watch now

Highlights of the Day: Gynecologic cancer

Gynecologic Cancer Video

Highlights of the Day: Breast Cancer – local/regional/adjuvant

Breast Cancer Video

Neoadjuvant dual immunotherapy improves melanoma outcomes

04-06-2024 Melanoma News

» View more highlights on the ASCO 2024 congress hub page

Webinar | 19-02-2024 | 17:30 (CET)

Keynote webinar | Spotlight on antibody–drug conjugates in cancer

Watch now

Antibody–drug conjugates (ADCs) are novel agents that have shown promise across multiple tumor types. Explore the current landscape of ADCs in breast and lung cancer with our experts, and gain insights into the mechanism of action, key clinical trials data, existing challenges, and future directions.

Dr. Véronique Diéras

Prof. Fabrice Barlesi

Developed by: Springer Medicine

Image Credits

ASCO 2024 | Highlights of the Day: Breast cancer – metastatic/© 2024 American Society of Clinical Oncology, all rights reserved., ASCO 2024 | Highlights of the Day: Gynecologic Cancer/© 2024 American Society of Clinical Oncology, all rights reserved., ASCO 2024 | Highlights of the Day: Breast Cancer – local/regional/adjuvant/© 2024 American Society of Clinical Oncology, all rights reserved., Melanoma/© selvanegra / Getty Images / iStock, Antibody drug conjugated with cytotoxic payload/© Love Employee / Getty images / iStock

2024 ASCO Annual Meeting

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 1/2021

Is more better? An analysis of toxicity and response outcomes from dose-finding clinical trials in cancer

Bevacizumab for radiation necrosis following radiotherapy of brain metastatic disease: a systematic review & meta-analysis

Bioinformatics and survival analysis of glia maturation factor-γ in pan-cancers

Co-expression of low-risk HPV E6/E7 and EBV LMP-1 leads to precancerous lesions by DNA damage

PD-1 inhibitors versus chemotherapy as second-line treatment for advanced esophageal squamous cell carcinoma: a meta-analysis