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Dose–risk relationships between cigarette smoking and ovarian cancer histotypes: a comprehensive meta-analysis

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Abstract

Purpose

Although smoking has not been associated with overall ovarian cancer risk, a different impact on various histotypes has been reported. Our aim is to provide an accurate, up-to-date estimate of the dose–risk relationships between cigarette smoking and epithelial ovarian cancer, overall and by histotypes.

Methods

Using an innovative approach for the identification of original study publications, we conducted a systematic review and meta-analysis of epidemiological studies published on the topic until September 2018. Summary relative risks (RR) for cigarette smoking were estimated using random-effects models; dose–risk relationships were evaluated using one-stage random-effects models with restricted cubic splines.

Results

Thirty-seven studies were considered in the meta-analysis. The summary RRs for current versus never smokers were 1.05 (95% confidence interval CI 0.95–1.16) for overall ovarian cancer, 1.78 (95% CI 1.52–2.07) for mucinous, 0.77 (95% CI 0.65–0.93) for clear cell, 0.81 (95% CI 0.73–0.91) for endometrioid, and 1.05 (95% CI 0.94; 1.17) for serous cancer. The risk of borderline mucinous (RR 2.09) and serous (RR 1.16) tumors was higher than for invasive cancers (RR 1.44 and 0.95, respectively). For mucinous cancer, risk was noticeably higher with smoking intensity and duration (RR 2.35 for 20 cigarettes/day, and 2.11 for 20 years of smoking). A non-significant linear relation was found with smoking intensity, duration, and time since quitting for overall ovarian cancer and other histotypes.

Conclusions

This uniquely large and comprehensive meta-analysis confirms that although cigarette smoking does not appear to be a risk factor for ovarian cancer, and it is even slightly protective for some rare histotypes, there is a strong dose–risk relationship with mucinous ovarian cancer.

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References

  1. Bray F, Ferlay J, Soerjomataram I et al (2018) Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 68:394–424

    Article  PubMed  Google Scholar 

  2. Wentzensen N, Poole EM, Trabert B et al (2016) Ovarian cancer risk factors by histologic subtype: an analysis from the ovarian cancer cohort consortium. J Clin Oncol 34:2888–2898

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. La Vecchia C (2017) Ovarian cancer: epidemiology and risk factors. Eur J Cancer Prev 26:55–62

    Article  CAS  PubMed  Google Scholar 

  4. Kurian AW, Balise RR, McGuire V, Whittemore AS (2005) Histologic types of epithelial ovarian cancer: have they different risk factors? Gynecol Oncol 96:520–530

    Article  PubMed  Google Scholar 

  5. International Agency for Research on Cancer (2012) IARC monograph on the evaluation of carcinogenic risks to humans. A review of human carcinogens—personal habits and indoor combustions. Volume 100E

  6. Beral V, Gaitskell K, Hermon C et al (2012) Ovarian cancer and smoking: individual participant meta-analysis including 28,114 women with ovarian cancer from 51 epidemiological studies. Lancet Oncol 13:946–956

    Article  CAS  PubMed  Google Scholar 

  7. Faber MT, Kjaer SK, Dehlendorff C et al (2013) Cigarette smoking and risk of ovarian cancer: a pooled analysis of 21 case–control studies. Cancer Causes Control 24:989–1004

    Article  PubMed  Google Scholar 

  8. Licaj I, Jacobsen BK, Selmer RM et al (2017) Smoking and risk of ovarian cancer by histological subtypes: an analysis among 300,000 Norwegian women. Br J Cancer 116:270–276

    Article  CAS  PubMed  Google Scholar 

  9. Licaj I, Lukic M, Jareid M et al (2016) Epithelial ovarian cancer subtypes attributable to smoking in the Norwegian Women and Cancer Study, 2012. Cancer Med 5:720–727

    Article  PubMed  PubMed Central  Google Scholar 

  10. Lugo A, Bosetti C, Peveri G et al (2017) Dose-response relationship between cigarette smoking and site-specific cancer risk: protocol for a systematic review with an original design combining umbrella and traditional reviews. BMJ Open 7:e018930

    PubMed  PubMed Central  Google Scholar 

  11. Nakamura K, Huxley R, Ansary-Moghaddam A, Woodward M (2009) The hazards and benefits associated with smoking and smoking cessation in Asia: a meta-analysis of prospective studies. Tob Control 18:345–353

    Article  CAS  PubMed  Google Scholar 

  12. Jordan SJ, Whiteman DC, Purdie DM et al (2006) Does smoking increase risk of ovarian cancer? A systematic review. Gynecol Oncol 103:1122–1129

    Article  CAS  PubMed  Google Scholar 

  13. IARC (2004) IARC monographs on the evaluation of carcinogenic risks to humans. Volume 83. Tobacco smoke and involuntary smoking. Lyon, France

  14. IARC (2012) IARC Monograph on the evaluation of carcinogenic risks to humans. Volume 100E. A review of human carcinogens—personal habits and indoor combustions. Lyon, France

  15. Hamling J, Lee P, Weitkunat R, Ambuhl M (2008) Facilitating meta-analyses by deriving relative effect and precision estimates for alternative comparisons from a set of estimates presented by exposure level or disease category. Stat Med 27:954–970

    Article  PubMed  Google Scholar 

  16. DerSimonian R, Laird N (1986) Meta-analysis in clinical trials. Control Clin Trials 7:177–188

    Article  CAS  PubMed  Google Scholar 

  17. Higgins JP, Thompson SG (2002) Quantifying heterogeneity in a meta-analysis. Stat Med 21:1539–1558

    Article  PubMed  Google Scholar 

  18. Peters JL, Sutton AJ, Jones DR et al (2008) Contour-enhanced meta-analysis funnel plots help distinguish publication bias from other causes of asymmetry. J Clin Epidemiol 61:991–996

    Article  PubMed  Google Scholar 

  19. Egger M, Smith GD, Schneider M, Minder C (1997) Bias in meta-analysis detected by a simple, graphical test. BMJ 315:629–634

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Crippa A, Discacciati A, Bottai M et al (2018) One-stage dose-response meta-analysis for aggregated data. Stat Methods Med Res 28:1579

    Article  PubMed  Google Scholar 

  21. Desquilbet L, Mariotti F (2010) Dose-response analyses using restricted cubic spline functions in public health research. Stat Med 29:1037–1057

    PubMed  Google Scholar 

  22. Lugo A, Peveri G, Bosetti C et al (2018) Strong excess risk of pancreatic cancer for low frequency and duration of cigarette smoking: a comprehensive review and meta-analysis. Eur J Cancer 104:117–126

    Article  PubMed  Google Scholar 

  23. Bagnardi V, Rota M, Botteri E et al (2015) Alcohol consumption and site-specific cancer risk: a comprehensive dose-response meta-analysis. Br J Cancer 112:580–593

    Article  CAS  PubMed  Google Scholar 

  24. Berlin JA, Longnecker MP, Greenland S (1993) Meta-analysis of epidemiologic dose-response data. Epidemiology 4:218–228

    Article  CAS  PubMed  Google Scholar 

  25. Crippa A, Orsini N (2016) Multivariate dose-response meta-analysis: the dosresmeta R Package. J Stat Soft 72:1

    Article  Google Scholar 

  26. Baron JA, Byers T, Greenberg ER et al (1986) Cigarette smoking in women with cancers of the breast and reproductive organs. J Natl Cancer Inst 77:677–680

    Article  CAS  PubMed  Google Scholar 

  27. Bodmer M, Becker C, Meier C et al (2011) Use of metformin and the risk of ovarian cancer: a case–control analysis. Gynecol Oncol 123:200–204

    Article  CAS  PubMed  Google Scholar 

  28. Franks AL, Lee NC, Kendrick JS et al (1987) Cigarette smoking and the risk of epithelial ovarian cancer. Am J Epidemiol 126:112–117

    Article  CAS  PubMed  Google Scholar 

  29. Fujita M, Tase T, Kakugawa Y et al (2008) Smoking, earlier menarche and low parity as independent risk factors for gynecologic cancers in Japanese: a case–control study. Tohoku J Exp Med 216:297–307

    Article  PubMed  Google Scholar 

  30. Goodman MT, Tung KH (2003) Active and passive tobacco smoking and the risk of borderline and invasive ovarian cancer (United States). Cancer Causes Control 14:569–577

    Article  PubMed  Google Scholar 

  31. Green A, Purdie D, Bain C et al (2001) Cigarette smoking and risk of epithelial ovarian cancer (Australia). Cancer Causes Control 12:713–719

    Article  CAS  PubMed  Google Scholar 

  32. Hartge P, Schiffman MH, Hoover R et al (1989) A case–control study of epithelial ovarian cancer. Am J Obstet Gynecol 161:10–16

    Article  CAS  PubMed  Google Scholar 

  33. Kelemen LE, Abbott S, Qin B et al (2017) Cigarette smoking and the association with serous ovarian cancer in African American women: African American cancer epidemiology study (AACES). Cancer Causes Control 28:699–708

    Article  PubMed  PubMed Central  Google Scholar 

  34. Kuper H, Titus-Ernstoff L, Harlow BL, Cramer DW (2000) Population based study of coffee, alcohol and tobacco use and risk of ovarian cancer. Int J Cancer 88:313–318

    Article  CAS  PubMed  Google Scholar 

  35. Marchbanks PA, Wilson H, Bastos E et al (2000) Cigarette smoking and epithelial ovarian cancer by histologic type. Obstet Gynecol 95:255–260

    CAS  PubMed  Google Scholar 

  36. Modugno F, Ness RB, Cottreau CM (2002) Cigarette smoking and the risk of mucinous and nonmucinous epithelial ovarian cancer. Epidemiology 13:467–471

    Article  PubMed  Google Scholar 

  37. Mori M, Nishida T, Sugiyama T et al (1998) Anthropometric and other risk factors for ovarian cancer in a case–control study. Jpn J Cancer Res 89:246–253

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  38. Pan SY, Ugnat AM, Mao Y et al (2004) Association of cigarette smoking with the risk of ovarian cancer. Int J Cancer 111:124–130

    Article  CAS  PubMed  Google Scholar 

  39. Pandeya N, Williams GM, Green AC et al (2009) Do low control response rates always affect the findings? Assessments of smoking and obesity in two Australian case–control studies of cancer. Aust N Z J Public Health 33:312–319

    Article  PubMed  Google Scholar 

  40. Polychronopoulou A, Tzonou A, Hsieh CC et al (1993) Reproductive variables, tobacco, ethanol, coffee and somatometry as risk factors for ovarian cancer. Int J Cancer 55:402–407

    Article  CAS  PubMed  Google Scholar 

  41. Riman T, Dickman PW, Nilsson S et al (2004) Some life-style factors and the risk of invasive epithelial ovarian cancer in Swedish women. Eur J Epidemiol 19:1011–1019

    Article  PubMed  Google Scholar 

  42. Slattery ML, Schuman KL, West DW et al (1989) Nutrient intake and ovarian cancer. Am J Epidemiol 130:497–502

    Article  CAS  PubMed  Google Scholar 

  43. Zhang Y, Coogan PF, Palmer JR et al (2004) Cigarette smoking and increased risk of mucinous epithelial ovarian cancer. Am J Epidemiol 159:133–139

    Article  PubMed  Google Scholar 

  44. Akiba S, Hirayama T (1990) Cigarette smoking and cancer mortality risk in Japanese men and women–results from reanalysis of the six-prefecture cohort study data. Environ Health Perspect 87:19–26

    CAS  PubMed  PubMed Central  Google Scholar 

  45. Akiba S (1994) Analysis of cancer risk related to longitudinal information on smoking habits. Environ Health Perspect 102(Suppl 8):15–19

    Article  PubMed  PubMed Central  Google Scholar 

  46. Blakely T, Barendregt JJ, Foster RH et al (2013) The association of active smoking with multiple cancers: national census-cancer registry cohorts with quantitative bias analysis. Cancer Causes Control 24:1243–1255

    Article  PubMed  Google Scholar 

  47. Carter BD, Abnet CC, Feskanich D et al (2015) Smoking and mortality–beyond established causes. N Engl J Med 372:631–640

    Article  CAS  PubMed  Google Scholar 

  48. Engeland A, Andersen A, Haldorsen T, Tretli S (1996) Smoking habits and risk of cancers other than lung cancer: 28 years’ follow-up of 26,000 Norwegian men and women. Cancer Causes Control 7:497–506

    Article  CAS  PubMed  Google Scholar 

  49. Gram IT, Braaten T, Adami HO et al (2008) Cigarette smoking and risk of borderline and invasive epithelial ovarian cancer. Int J Cancer 122:647–652

    Article  CAS  PubMed  Google Scholar 

  50. Gram IT, Lukanova A, Brill I et al (2012) Cigarette smoking and risk of histological subtypes of epithelial ovarian cancer in the EPIC cohort study. Int J Cancer 130:2204–2210

    Article  CAS  PubMed  Google Scholar 

  51. Kenfield SA, Stampfer MJ, Rosner BA, Colditz GA (2008) Smoking and smoking cessation in relation to mortality in women. JAMA 299:2037–2047

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Niwa Y, Wakai K, Suzuki S et al (2005) Cigarette smoking and the risk of ovarian cancer in the Japanese population: findings from the Japanese Collaborate Cohort study. J Obstet Gynaecol Res 31:144–151

    Article  PubMed  Google Scholar 

  53. Pirie K, Peto R, Reeves GK et al (2013) The 21st century hazards of smoking and benefits of stopping: a prospective study of one million women in the UK. Lancet 381:133–141

    Article  PubMed  PubMed Central  Google Scholar 

  54. Terry PD, Miller AB, Jones JG, Rohan TE (2003) Cigarette smoking and the risk of invasive epithelial ovarian cancer in a prospective cohort study. Eur J Cancer 39:1157–1164

    Article  CAS  PubMed  Google Scholar 

  55. Tverdal A, Thelle D, Stensvold I et al (1993) Mortality in relation to smoking history: 13 years’ follow-up of 68,000 Norwegian men and women 35–49 years. J Clin Epidemiol 46:475–487

    Article  CAS  PubMed  Google Scholar 

  56. Tworoger SS, Gertig DM, Gates MA et al (2008) Caffeine, alcohol, smoking, and the risk of incident epithelial ovarian cancer. Cancer 112:1169–1177

    Article  PubMed  Google Scholar 

  57. Weiderpass E, Sandin S, Inoue M et al (2012) Risk factors for epithelial ovarian cancer in Japan—results from the Japan Public Health Center-based Prospective Study cohort. Int J Oncol 40:21–30

    PubMed  Google Scholar 

  58. Gilks CB, Prat J (2009) Ovarian carcinoma pathology and genetics: recent advances. Hum Pathol 40:1213–1223

    Article  CAS  PubMed  Google Scholar 

  59. Kurman RJ, Shih IM (2010) The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory. Am J Surg Pathol 34:433–443

    Article  PubMed  PubMed Central  Google Scholar 

  60. Baykara O, Tansarikaya M, Demirkaya A et al (2013) Association of epidermal growth factor receptor and K-Ras mutations with smoking history in non-small cell lung cancer patients. Exp Ther Med 5:495–498

    Article  CAS  PubMed  Google Scholar 

  61. Mayr D, Hirschmann A, Lohrs U, Diebold J (2006) KRAS and BRAF mutations in ovarian tumors: a comprehensive study of invasive carcinomas, borderline tumors and extraovarian implants. Gynecol Oncol 103:883–887

    Article  CAS  PubMed  Google Scholar 

  62. Morales NA, Romano MA, Cummings KM et al (2013) Accuracy of self-reported tobacco use in newly diagnosed cancer patients. Cancer Causes Control 24:1223–1230

    Article  PubMed  PubMed Central  Google Scholar 

  63. Gallus S, Muttarak R, Franchi M et al (2013) Why do smokers quit? Eur J Cancer Prev 22:96–101

    Article  PubMed  Google Scholar 

  64. Kurman RJ, Carcangiu ML, Herrington CS, Young RH (2014) WHO/IARC classification of tumours of female reproductive organs, 4th edn. France, Lyon

    Google Scholar 

  65. Perren TJ (2016) Mucinous epithelial ovarian carcinoma. Ann Oncol 27(Suppl 1):i53–i57

    Article  PubMed  Google Scholar 

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Acknowledgments

The authors thank Dr. J.D. Baggott for language editing.

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Authors and Affiliations

  1. Department of Oncology, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Milan, Italy

    Claudia Santucci & Cristina Bosetti

  2. Department of Molecular and Translational Medicine, Università degli Studi di Brescia, Brescia, Italy

    Giulia Peveri & Claudia Specchia

  3. Laboratory of Lifestyle Epidemiology, Department of Environmental Health Sciences, Istituto di Ricerche Farmacologiche Mario Negri IRCCS, Via Mario Negri 2, 20156, Milan, Italy

    Xiaoqiu Liu, Silvano Gallus & Alessandra Lugo

  4. Department of Statistics and Quantitative Methods, Università degli Studi di Milano-Bicocca, Milan, Italy

    Vincenzo Bagnardi

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  1. Claudia Santucci
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  2. Cristina Bosetti
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  4. Xiaoqiu Liu
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  5. Vincenzo Bagnardi
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  8. Alessandra Lugo
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Contributions

SG and AL had the original study idea and designed the innovative methodology for the identification of original publications. AL, CSa, and XL identified the publications, extracted the data, and did the statistical analyses, with the help of GP. CSa, CB, SG, and AL wrote the manuscript. CB, VB, and CSp provided statistical and epidemiological supervision. All authors contributed to critically reviewing and revising the draft manuscript, and approval of its final version.

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Correspondence to Silvano Gallus.

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Santucci, C., Bosetti, C., Peveri, G. et al. Dose–risk relationships between cigarette smoking and ovarian cancer histotypes: a comprehensive meta-analysis. Cancer Causes Control 30, 1023–1032 (2019). https://doi.org/10.1007/s10552-019-01198-8

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