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. 2001 Mar;84(5):722–727. doi: 10.1054/bjoc.2000.1622

Oral contraceptives and colorectal cancer risk: a meta-analysis

E Fernandez 1,2, C La Vecchia 2,3, A Balducci 2, L Chatenoud 2, S Franceschi 4, E Negri 2
PMCID: PMC2363788  PMID: 11237397

Abstract

Several studies have suggested an inverse association between use of combined oral contraceptives (OC) and the risk of colorectal cancer and here we present a meta-analysis of published studies. Articles considered were epidemiological studies published as full papers in English up to June 2000 that included quantitative information on OC use. The pooled relative risks (RR) of colorectal cancer for ever OC use from the 8 case-control studies was 0.81 (95% confidence interval (CI): 0.69–0.94), and the pooled estimate from the 4 cohort studies was 0.84 (95% CI: 0.72–0.97). The pooled estimate from all studies combined was 0.82 (95% CI: 0.74–0.92), without apparent heterogeneity. Duration of use was not associated with a decrease in risk, but there was some indication that the apparent protection was stronger for women who had used OCs more recently (RR = 0.46; 95% CI: 0.30–0.71). A better understanding of this potential relation may help informed choice of contraception. © 2001 Cancer Research Campaign http://www.bjcancer.com

Keywords: colorectal neoplasms, oral contraceptives, female hormones, meta-analysis

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Selected References

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  1. Beral V., Hermon C., Kay C., Hannaford P., Darby S., Reeves G. Mortality associated with oral contraceptive use: 25 year follow up of cohort of 46 000 women from Royal College of General Practitioners' oral contraception study. BMJ. 1999 Jan 9;318(7176):96–100. doi: 10.1136/bmj.318.7176.96. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Bostick R. M., Potter J. D., Kushi L. H., Sellers T. A., Steinmetz K. A., McKenzie D. R., Gapstur S. M., Folsom A. R. Sugar, meat, and fat intake, and non-dietary risk factors for colon cancer incidence in Iowa women (United States). Cancer Causes Control. 1994 Jan;5(1):38–52. doi: 10.1007/BF01830725. [DOI] [PubMed] [Google Scholar]
  3. Campagnoli C., Biglia N., Cantamessa C., Lesca L., Lotano M. R., Sismondi P. Insulin-like growth factor I (IGF-I) serum level modifications during transdermal estradiol treatment in postmenopausal women: a possible bimodal effect depending on basal IGF-I values. Gynecol Endocrinol. 1998 Aug;12(4):259–266. doi: 10.3109/09513599809015598. [DOI] [PubMed] [Google Scholar]
  4. Chute C. G., Willett W. C., Colditz G. A., Stampfer M. J., Rosner B., Speizer F. E. A prospective study of reproductive history and exogenous estrogens on the risk of colorectal cancer in women. Epidemiology. 1991 May;2(3):201–207. doi: 10.1097/00001648-199105000-00007. [DOI] [PubMed] [Google Scholar]
  5. Dickersin K., Min Y. I. Publication bias: the problem that won't go away. Ann N Y Acad Sci. 1993 Dec 31;703:135–148. doi: 10.1111/j.1749-6632.1993.tb26343.x. [DOI] [PubMed] [Google Scholar]
  6. Egger M., Davey Smith G., Schneider M., Minder C. Bias in meta-analysis detected by a simple, graphical test. BMJ. 1997 Sep 13;315(7109):629–634. doi: 10.1136/bmj.315.7109.629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Fernandez E., Bosetti C., La Vecchia C., Levi F., Fioretti F., Negri E. Sex differences in colorectal cancer mortality in Europe, 1955-1996. Eur J Cancer Prev. 2000 Apr;9(2):99–104. doi: 10.1097/00008469-200004000-00005. [DOI] [PubMed] [Google Scholar]
  8. Fernandez E., La Vecchia C., D'Avanzo B., Franceschi S., Negri E., Parazzini F. Oral contraceptives, hormone replacement therapy and the risk of colorectal cancer. Br J Cancer. 1996 Jun;73(11):1431–1435. doi: 10.1038/bjc.1996.272. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Fernandez E., La Vecchia C., Franceschi S., Braga C., Talamini R., Negri E., Parazzini F. Oral contraceptive use and risk of colorectal cancer. Epidemiology. 1998 May;9(3):295–300. [PubMed] [Google Scholar]
  10. Franceschi S., Bidoli E., Talamini R., Barra S., La Vecchia C. Colorectal cancer in northeast Italy: reproductive, menstrual and female hormone-related factors. Eur J Cancer. 1991;27(5):604–608. doi: 10.1016/0277-5379(91)90228-6. [DOI] [PubMed] [Google Scholar]
  11. Franceschi S., La Vecchia C. Oral contraceptives and colorectal tumors. A review of epidemiologic studies. Contraception. 1998 Dec;58(6):335–343. doi: 10.1016/s0010-7824(98)00128-0. [DOI] [PubMed] [Google Scholar]
  12. Fraumeni J. F., Jr, Lloyd J. W., Smith E. M., Wagoner J. K. Cancer mortality among nuns: role of marital status in etiology of neoplastic disease in women. J Natl Cancer Inst. 1969 Mar;42(3):455–468. [PubMed] [Google Scholar]
  13. Furner S. E., Davis F. G., Nelson R. L., Haenszel W. A case-control study of large bowel cancer and hormone exposure in women. Cancer Res. 1989 Sep 1;49(17):4936–4940. [PubMed] [Google Scholar]
  14. Galbraith R. F. A note on graphical presentation of estimated odds ratios from several clinical trials. Stat Med. 1988 Aug;7(8):889–894. doi: 10.1002/sim.4780070807. [DOI] [PubMed] [Google Scholar]
  15. Gerhardsson de Verdier M., London S. Reproductive factors, exogenous female hormones, and colorectal cancer by subsite. Cancer Causes Control. 1992 Jul;3(4):355–360. doi: 10.1007/BF00146889. [DOI] [PubMed] [Google Scholar]
  16. Giovannucci E., Pollak M. N., Platz E. A., Willett W. C., Stampfer M. J., Majeed N., Colditz G. A., Speizer F. E., Hankinson S. E. A prospective study of plasma insulin-like growth factor-1 and binding protein-3 and risk of colorectal neoplasia in women. Cancer Epidemiol Biomarkers Prev. 2000 Apr;9(4):345–349. [PubMed] [Google Scholar]
  17. Greenland S. Quantitative methods in the review of epidemiologic literature. Epidemiol Rev. 1987;9:1–30. doi: 10.1093/oxfordjournals.epirev.a036298. [DOI] [PubMed] [Google Scholar]
  18. Hébert-Croteau N. A meta-analysis of hormone replacement therapy and colon cancer in women. Cancer Epidemiol Biomarkers Prev. 1998 Aug;7(8):653–659. [PubMed] [Google Scholar]
  19. Issa J. P., Ottaviano Y. L., Celano P., Hamilton S. R., Davidson N. E., Baylin S. B. Methylation of the oestrogen receptor CpG island links ageing and neoplasia in human colon. Nat Genet. 1994 Aug;7(4):536–540. doi: 10.1038/ng0894-536. [DOI] [PubMed] [Google Scholar]
  20. Jacobs E. J., White E., Weiss N. S. Exogenous hormones, reproductive history, and colon cancer (Seattle, Washington, USA). Cancer Causes Control. 1994 Jul;5(4):359–366. doi: 10.1007/BF01804987. [DOI] [PubMed] [Google Scholar]
  21. Kampman E., Bijl A. J., Kok C., van't Veer P. Reproductive and hormonal factors in male and female colon cancer. Eur J Cancer Prev. 1994 Jul;3(4):329–336. doi: 10.1097/00008469-199407000-00005. [DOI] [PubMed] [Google Scholar]
  22. Kampman E., Potter J. D., Slattery M. L., Caan B. J., Edwards S. Hormone replacement therapy, reproductive history, and colon cancer: a multicenter, case-control study in the United States. Cancer Causes Control. 1997 Mar;8(2):146–158. doi: 10.1023/a:1018459911147. [DOI] [PubMed] [Google Scholar]
  23. Kune G. A., Kune S., Watson L. F. Oral contraceptive use does not protect against large bowel cancer. Contraception. 1990 Jan;41(1):19–25. doi: 10.1016/0010-7824(90)90123-d. [DOI] [PubMed] [Google Scholar]
  24. La Vecchia C., Negri E., Levi F., Decarli A., Boyle P. Cancer mortality in Europe: effects of age, cohort of birth and period of death. Eur J Cancer. 1998 Jan;34(1):118–141. doi: 10.1016/s0959-8049(97)00335-3. [DOI] [PubMed] [Google Scholar]
  25. La Vecchia C., Tavani A., Franceschi S., Parazzini F. Oral contraceptives and cancer. A review of the evidence. Drug Saf. 1996 Apr;14(4):260–272. doi: 10.2165/00002018-199614040-00006. [DOI] [PubMed] [Google Scholar]
  26. Lointier P., Wildrick D. M., Boman B. M. The effects of steroid hormones on a human colon cancer cell line in vitro. Anticancer Res. 1992 Jul-Aug;12(4):1327–1330. [PubMed] [Google Scholar]
  27. Martínez M. E., Grodstein F., Giovannucci E., Colditz G. A., Speizer F. E., Hennekens C., Rosner B., Willett W. C., Stampfer M. J. A prospective study of reproductive factors, oral contraceptive use, and risk of colorectal cancer. Cancer Epidemiol Biomarkers Prev. 1997 Jan;6(1):1–5. [PubMed] [Google Scholar]
  28. McMichael A. J., Potter J. D. Host factors in carcinogenesis: certain bile-acid metabolic profiles that selectively increase the risk of proximal colon cancer. J Natl Cancer Inst. 1985 Aug;75(2):185–191. [PubMed] [Google Scholar]
  29. Negri E., La Vecchia C., Parazzini F., Savoldelli R., Gentile A., D'Avanzo B., Gramenzi A., Franceschi S. Reproductive and menstrual factors and risk of colorectal cancer. Cancer Res. 1989 Dec 15;49(24 Pt 1):7158–7161. [PubMed] [Google Scholar]
  30. Peters R. K., Pike M. C., Chang W. W., Mack T. M. Reproductive factors and colon cancers. Br J Cancer. 1990 May;61(5):741–748. doi: 10.1038/bjc.1990.166. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Potter J. D. Colorectal cancer: molecules and populations. J Natl Cancer Inst. 1999 Jun 2;91(11):916–932. doi: 10.1093/jnci/91.11.916. [DOI] [PubMed] [Google Scholar]
  32. Potter J. D., McMichael A. J. Large bowel cancer in women in relation to reproductive and hormonal factors: a case-control study. J Natl Cancer Inst. 1983 Oct;71(4):703–709. [PubMed] [Google Scholar]
  33. Potter J. D., Slattery M. L., Bostick R. M., Gapstur S. M. Colon cancer: a review of the epidemiology. Epidemiol Rev. 1993;15(2):499–545. doi: 10.1093/oxfordjournals.epirev.a036132. [DOI] [PubMed] [Google Scholar]
  34. Risch H. A., Howe G. R. Menopausal hormone use and colorectal cancer in Saskatchewan: a record linkage cohort study. Cancer Epidemiol Biomarkers Prev. 1995 Jan-Feb;4(1):21–28. [PubMed] [Google Scholar]
  35. Talamini R., Franceschi S., Dal Maso L., Negri E., Conti E., Filiberti R., Montella M., Nanni O., La Vecchia C. The influence of reproductive and hormonal factors on the risk of colon and rectal cancer in women. Eur J Cancer. 1998 Jun;34(7):1070–1076. doi: 10.1016/s0959-8049(98)00019-7. [DOI] [PubMed] [Google Scholar]
  36. Thomas M. L., Xu X., Norfleet A. M., Watson C. S. The presence of functional estrogen receptors in intestinal epithelial cells. Endocrinology. 1993 Jan;132(1):426–430. doi: 10.1210/endo.132.1.8419141. [DOI] [PubMed] [Google Scholar]
  37. Thornton A., Lee P. Publication bias in meta-analysis: its causes and consequences. J Clin Epidemiol. 2000 Feb;53(2):207–216. doi: 10.1016/s0895-4356(99)00161-4. [DOI] [PubMed] [Google Scholar]
  38. Troisi R., Schairer C., Chow W. H., Schatzkin A., Brinton L. A., Fraumeni J. F., Jr Reproductive factors, oral contraceptive use, and risk of colorectal cancer. Epidemiology. 1997 Jan;8(1):75–79. doi: 10.1097/00001648-199701000-00012. [DOI] [PubMed] [Google Scholar]
  39. Weiss N. S., Daling J. R., Chow W. H. Incidence of cancer of the large bowel in women in relation to reproductive and hormonal factors. J Natl Cancer Inst. 1981 Jul;67(1):57–60. [PubMed] [Google Scholar]
  40. Wu-Williams A. H., Lee M., Whittemore A. S., Gallagher R. P., Jiao D. A., Zheng S., Zhou L., Wang X. H., Chen K., Jung D. Reproductive factors and colorectal cancer risk among Chinese females. Cancer Res. 1991 May 1;51(9):2307–2311. [PubMed] [Google Scholar]
  41. dos Santos Silva I., Swerdlow A. J. Sex differences in time trends of colorectal cancer in England and Wales: the possible effect of female hormonal factors. Br J Cancer. 1996 Mar;73(5):692–697. doi: 10.1038/bjc.1996.120. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. el Atiq F., Garrouste F., Remacle-Bonnet M., Sastre B., Pommier G. Alterations in serum levels of insulin-like growth factors and insulin-like growth-factor-binding proteins in patients with colorectal cancer. Int J Cancer. 1994 May 15;57(4):491–497. doi: 10.1002/ijc.2910570409. [DOI] [PubMed] [Google Scholar]
  43. van Wayenburg C. A., van der Schouw Y. T., van Noord P. A., Peeters P. H. Age at menopause, body mass index, and the risk of colorectal cancer mortality in the Dutch Diagnostisch Onderzoek Mammacarcinoom (DOM) cohort. Epidemiology. 2000 May;11(3):304–308. doi: 10.1097/00001648-200005000-00013. [DOI] [PubMed] [Google Scholar]

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