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Meta-analysis of Studies of Alcohol and Breast Cancer with Consideration of the Methodological Issues

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Abstract

Objective

To give an up-to-date assessment of the association of alcohol with female breast cancer, addressing methodological issues and shortfalls in previous overviews.

Methods

Meta-analysis of studies (any language) providing original data on incidence of first primary breast cancer and alcohol. Two reviewers independently extracted data. Study quality assessed by objective criteria including degree of control for confounding; funnel plots examined for publication bias; meta-regression techniques to explore heterogeneity. Risks associated with drinking versus not drinking and dose–response not constrained through the origin estimated using random effects methods.

Results

Ninety-eight unique studies were included, involving 75,728 and 60,653 cases in drinker versus non-drinker and dose–response analyses, respectively. Findings were robust to study design and analytic approaches in the meta-analyses. For studies judged high quality, controlled for appropriate confounders, excess risk associated with alcohol drinking was 22% (95% CI: 9–37%); each additional 10 g ethanol/day was associated with risk higher by 10% (95% CI: 5–15%). There was no evidence of publication bias. Risk did not differ significantly by beverage type or menopausal status. Estimated population attributable risks were 1.6 and 6.0% in USA and UK, respectively.

Conclusions

Taking account of shortcomings in the study base and methodological concerns, we confirm the alcohol–breast cancer association. We compared our results to those of an individual patient data analysis, with similar findings. We conclude that the association between alcohol and breast cancer may be causal.

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References

  1. Sutton AJ, Abrams KR, Jones DR, Sheldon TA, Song F (2000) Methods for meta-analysis in medical research. Wiley

  2. M Egger M Schneider G Davey Smith (1998) ArticleTitleSpurious precision? Meta-analysis of observational studies BMJ 316 140–144 Occurrence Handle9462324 Occurrence Handle1:STN:280:DyaK1c7itlyktA%3D%3D

    PubMed  CAS  Google Scholar 

  3. MP Longnecker JA Berlin MJ Orza TC Chalmers (1988) ArticleTitleA meta-analysis of alcohol consumption in relation to risk of breast cancer JAMA 260 652–656 Occurrence Handle3392790 Occurrence Handle1:STN:280:BieB2srhtVA%3D Occurrence Handle10.1001/jama.260.5.652

    Article  PubMed  CAS  Google Scholar 

  4. MP Longnecker (1994) ArticleTitleAlcoholic beverage consumption in relation to risk of breast cancer: meta-analysis and review Cancer Cause Control 5 73–82 Occurrence Handle1:STN:280:ByuC28bivFU%3D Occurrence Handle10.1007/BF01830729

    Article  CAS  Google Scholar 

  5. HD Roth PS Levy L Shi E Post (1994) ArticleTitleAlcoholic beverages and breast cancer: some observations on published case–control studies J Clin Epidemiol 47 207–216 Occurrence Handle8113830 Occurrence Handle1:STN:280:ByuC2MjlvFE%3D Occurrence Handle10.1016/0895-4356(94)90026-4

    Article  PubMed  CAS  Google Scholar 

  6. RC Ellison Y Zhang CE McLennan KJ Rothman (2001) ArticleTitleExploring the relation of alcohol consumption to risk of breast cancer Am J Epidemiol 154 740–747 Occurrence Handle11590087 Occurrence Handle1:STN:280:DC%2BD3MrktlCmtw%3D%3D Occurrence Handle10.1093/aje/154.8.740

    Article  PubMed  CAS  Google Scholar 

  7. V Bagnardi M Blangiardo C La Vecchia G Corrao (2001) ArticleTitleA meta-analysis of alcohol drinking and cancer risk Br J Cancer 85 1700–1705 Occurrence Handle11742491 Occurrence Handle1:CAS:528:DC%2BD38XnsVChtg%3D%3D Occurrence Handle10.1054/bjoc.2001.2140

    Article  PubMed  CAS  Google Scholar 

  8. Collaborative Group on Hormonal Factors in Breast Cancer (2002) Alcohol, tobacco and breast cancer – collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. Br J Cancer 87:1234–1245

    Google Scholar 

  9. C Turner (1990) ArticleTitleHow much alcohol is in a “standard drink”? An analysis of 125 studies Brit J Addiction 85 1171–1175 Occurrence Handle1:STN:280:By6D38fjt1E%3D Occurrence Handle10.1111/j.1360-0443.1990.tb03442.x

    Article  CAS  Google Scholar 

  10. R Dersimonian N Laird (1986) ArticleTitleMeta-analysis in clinical trials Control Clin Trials 7 177–188 Occurrence Handle3802833 Occurrence Handle1:STN:280:BiiC3cvisFI%3D Occurrence Handle10.1016/0197-2456(86)90046-2

    Article  PubMed  CAS  Google Scholar 

  11. LV Hedges I Olkin (1985) Statistical methods for meta-analysis Academic Press Orlando, FL

    Google Scholar 

  12. S Greenland MP Longnecker (1992) ArticleTitleMethods for trend estimation from summarized dose–response data, with applications to meta-analysis Am J Epidemiol 135 1301–1309 Occurrence Handle1626547 Occurrence Handle1:STN:280:By2A38fgt1I%3D

    PubMed  CAS  Google Scholar 

  13. SG Thompson SJ Sharp (1999) ArticleTitleExplaining heterogeneity in meta-analysis: a comparison of methods Stats Med 18 2693–2709 Occurrence Handle1:STN:280:DyaK1MvltlWhtA%3D%3D Occurrence Handle10.1002/(SICI)1097-0258(19991030)18:20<2693::AID-SIM235>3.0.CO;2-V

    Article  CAS  Google Scholar 

  14. JA Hanley (2001) ArticleTitleA heuristic approach to the formulas for population attributable risk J Epidemiol Community Health 55 508–514 Occurrence Handle11413183 Occurrence Handle1:STN:280:DC%2BD3MzkvFOqtQ%3D%3D Occurrence Handle10.1136/jech.55.7.508

    Article  PubMed  CAS  Google Scholar 

  15. http://www.doh.gov.uk/stats/tables/atrend9811.xls, accessed Jan 2003 http://www.show.scot.nhs.uk/scottishhealthsurvey/sh809–04.html, accessed Jan 2003

  16. Schoenborn CA, Dams PF (2001) Alcohol use among adults: United States, 1997–98. Advance data from vital and health statistics; No. 324. National Center for Health Statistics, Hyattsville, Maryland

  17. SEER Cancer Statistics Review 1973–1994. National Cancer Institute

  18. Cancer statistic registrations for England, 1998, http://www.wales.nhs.uk/sites/documents/242/CancerIncidence1992–2001.pdf, accessed Jan 2003 http://www.show.scot.nhs.uk/isd/cancer/excel/female_breast_1b.xls, accessed Jan 2003 http://researchservices1.qub.ac.uk/nicr/incidence_search.htm, accessed Jan 2003

  19. B Hedges P di Salvo (1998) Alcohol consumption and smoking P Prescott-Clarke P Primatesta (Eds) The health survey for England 1996 The Stationery Office London

    Google Scholar 

  20. RJ Light DB Pillemar (1984) Summing up: the science of reviewing research Harvard University Press Cambridge, MA

    Google Scholar 

  21. S Greenland K O’Rourke (2001) ArticleTitleOn the bias produced by quality scores in meta-analysis, and a hierarchical view of proposed solutions Biostatistics 2 463–471 Occurrence Handle12933636 Occurrence Handle1:STN:280:DC%2BD3szpsFChuw%3D%3D Occurrence Handle10.1093/biostatistics/2.4.463

    Article  PubMed  CAS  Google Scholar 

  22. J Rehm (1998) ArticleTitleMeasuring quantity, frequency and volume of drinking. Alcoholism Clin Exp Res 22 4S–14S Occurrence Handle1:STN:280:DyaK1c3msVCnsg%3D%3D Occurrence Handle10.1111/j.1530-0277.1998.tb04368.x

    Article  CAS  Google Scholar 

  23. M Tseng CR Weinberg DM Umbach MP Longnecker (1999) ArticleTitleCalculation of population attributable risk for alcohol and breast cancer Cancer Cause Control 10 119–123 Occurrence Handle1:STN:280:DyaK1M3ks1Wqsw%3D%3D Occurrence Handle10.1023/A:1008853115901

    Article  CAS  Google Scholar 

  24. O Niemela S Parkkila RO Juvonen K Viitala HV Gelboin M Pasanen (2000) ArticleTitleCytochromes P450 2A6, 2E1, and 3A and production of protein–aldehyde adducts in the liver of patients with alcoholic and non-alcoholic liver diseases J Hepatol 33 893–901 Occurrence Handle11131450 Occurrence Handle1:CAS:528:DC%2BD3cXovVKjsLg%3D Occurrence Handle10.1016/S0168-8278(00)80120-8

    Article  PubMed  CAS  Google Scholar 

  25. GL Kedderis R Batra DR Koop (1993) ArticleTitleEpoxidation of acrylonitrile by rat and human cytochromes P450 Chem Res Toxicol 6 866–871 Occurrence Handle8117926 Occurrence Handle1:CAS:528:DyaK3sXmsVegtL8%3D Occurrence Handle10.1021/tx00036a017

    Article  PubMed  CAS  Google Scholar 

  26. PF Swann (1984) ArticleTitleEffect of ethanol on nitrosamine metabolism and distribution. Implications for the role of nitrosamines in human cancer and for the influence of alcohol consumption on cancer incidence IARC Sci Publ 57 501–512 Occurrence Handle6533040 Occurrence Handle1:CAS:528:DyaL2MXks1Knuro%3D

    PubMed  CAS  Google Scholar 

  27. SR Dunn ML Simenhoff PS Lele S Goyal JW Pensabene W Fiddler (1990) ArticleTitleN-nitrosodimethylamine blood levels in patients with chronic renal failure: modulation of levels by ethanol and ascorbic acid J Natl Cancer Inst 82 783–787 Occurrence Handle2325149 Occurrence Handle1:STN:280:By%2BB3MbhtVU%3D

    PubMed  CAS  Google Scholar 

  28. SK Chhabra VL Souliotis SA Kyrtopoulos LM Anderson (1996) ArticleTitleNitrosamines, alcohol, and gastrointestinal tract cancer: recent epidemiology and experimentation In Vivo 10 265–284 Occurrence Handle8797028 Occurrence Handle1:CAS:528:DyaK28XksVOiu7k%3D

    PubMed  CAS  Google Scholar 

  29. E Funkhouser JW Waterbor P Cole E Rubin (1993) ArticleTitleMammographic patterns and breast cancer risk factors among women having elective screening South Med J 86 177–180 Occurrence Handle8434288 Occurrence Handle1:STN:280:ByyC28njt1U%3D

    PubMed  CAS  Google Scholar 

  30. CM Vachon LH Kushi JR Cerhan CC Kuni TA Sellers (2000) ArticleTitleAssociation of diet and mammographic breast density in the Minnesota breast cancer family cohort Cancer Epidemiol Biomarkers Prev 9 151–160 Occurrence Handle10698475 Occurrence Handle1:CAS:528:DC%2BD3cXitF2qtb8%3D

    PubMed  CAS  Google Scholar 

  31. CM Vachon CC Kuni K Anderson VE Anderson TA Sellers (2000) ArticleTitleAssociation of mammographically defined percent breast density with epidemiologic risk factors for breast cancer (United States) Cancer Cause Control 11 653–662 Occurrence Handle1:STN:280:DC%2BD3M7ht1CrtA%3D%3D Occurrence Handle10.1023/A:1008926607428

    Article  CAS  Google Scholar 

  32. C Byrne GA Colditz WC Willett FE Speizer M Pollak SE Hankinson (2000) ArticleTitlePlasma insulin-like growth factor (IGF) I, IGF-binding protein 3, and mammographic density Cancer Res 60 3744–3748 Occurrence Handle10919644 Occurrence Handle1:CAS:528:DC%2BD3cXlt1Gktrs%3D

    PubMed  CAS  Google Scholar 

  33. H Yu J Berkel (1999) ArticleTitleDo insulin-like growth factors mediate the effect of alcohol on breast cancer risk? Med Hypotheses 52 491–496 Occurrence Handle10459827 Occurrence Handle1:CAS:528:DyaK1MXltlOiur8%3D Occurrence Handle10.1054/mehy.1998.0828

    Article  PubMed  CAS  Google Scholar 

  34. TJA Key MC Pike (1988) ArticleTitleThe role of oestrogen and progestogens in the epidemiology and prevention of breast cancer Eur J Cancer Clin Oncol 24 29–43 Occurrence Handle3276531 Occurrence Handle1:STN:280:BieC3M7osFQ%3D Occurrence Handle10.1016/0277-5379(88)90173-3

    Article  PubMed  CAS  Google Scholar 

  35. ME Reichman JT Judd C Longcope A Schatzkin (1993) ArticleTitleEffects of alcohol consumption on plasma and urinary hormone concentrations in premenopausal women J Natl Cancer Inst 85 722–727 Occurrence Handle8478958 Occurrence Handle1:STN:280:ByyB2c%2Fls1Q%3D

    PubMed  CAS  Google Scholar 

  36. JF Dorgan DJ Baer PS Albert et al. (2001) ArticleTitleSerum hormones and the alcohol–breast cancer association in postmenopausal women J Natl Cancer Inst 93 710–715 Occurrence Handle11333294 Occurrence Handle1:CAS:528:DC%2BD3MXjvVamu7g%3D Occurrence Handle10.1093/jnci/93.9.710

    Article  PubMed  CAS  Google Scholar 

  37. J Gill (2000) ArticleTitleThe effects of moderate alcohol consumption on female hormone levels and reproductive function Alcohol 35 417–423 Occurrence Handle1:CAS:528:DC%2BD3cXnvV2msro%3D

    CAS  Google Scholar 

  38. SE Hankinson WC Willett JE Manson et al. (1995) ArticleTitleAlcohol, height, and adiposity in relation to estrogen and prolactin levels in postmenopausal women J Natl Cancer Inst 87 1297–1302 Occurrence Handle7658481 Occurrence Handle1:CAS:528:DyaK2MXotlygtbk%3D

    PubMed  CAS  Google Scholar 

  39. Henderson BE, Pike MC, Bernstein L, Ross RK (1996) Breast Cancer. In: Schottenfeld D, Fraumeni JF Jr (eds) Cancer epidemiology and prevention, 2nd edn. Oxford University Press, pp 1022–1039

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Acknowledgments

Study funded by the Department of Health in England. Authors gratefully acknowledge advice and comments from members and secretariat of the Committee on Carcinogenicity of the Department of Health. Grant support for this work was by UK Department of Health (META-ANLAYSIS/99).

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Correspondence to Paul Elliott.

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Key, J., Hodgson, S., Omar, R.Z. et al. Meta-analysis of Studies of Alcohol and Breast Cancer with Consideration of the Methodological Issues. Cancer Causes Control 17, 759–770 (2006). https://doi.org/10.1007/s10552-006-0011-0

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  • DOI: https://doi.org/10.1007/s10552-006-0011-0

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