title: Causes of infertility as predictors of subsequent cancer risk.
abstract: BACKGROUND
  Although studies have found elevated risks of certain cancers linked to infertility, the underlying reasons remain unclear.
  
  
  METHODS
  In a retrospective cohort study of 12,193 U.S. women evaluated for infertility between 1965 and 1988, 581 cases of cancer were identified through 1999. We used standardized incidence ratios (SIRs) to compare cancer risk with the general population. Analyses within the cohort estimated rate ratios (RRs) associated with infertility after adjusting for other risk predictors.
  
  
  RESULTS
  Infertility patients demonstrated a higher cancer risk than the general population (SIR = 1.23; 95% confidence interval [CI] = 1.1-1.3), with nulligravid (primary infertility) patients at even higher risk (1.43; 1.3-1.6). Particularly elevated risks among primary infertility patients were observed for cancers of the uterus (1.93) and ovaries (2.73). Analyses within the cohort revealed increased RRs of colon, ovarian, and thyroid cancers, and of melanomas associated with endometriosis. Melanomas were linked with anovulatory problems, whereas uterine cancers predominated among patients with tubal disorders. When primary infertility patients with specific causes of infertility were compared with unaffected patients who had secondary infertility, endometriosis was linked with distinctive excesses of cancers of the colon (RR = 2.40; 95% CI = 0.7-8.4), ovaries (2.88; 1.2-7.1), and thyroid (4.65; 0.8-25.6) cancers, as well as melanomas (2.32; 0.8-6.7). Primary infertility due to anovulation particularly predisposed to uterine cancer (2.42; 1.0-5.8), and tubal disorders to ovarian cancer (1.61; 0.7-3.8). Primary infertility associated with male-factor problems was associated with unexpected increases in colon (2.85; 0.9-9.5) and uterine (3.15; 1.0-9.5) cancers.
  
  
  CONCLUSIONS
  The effects of infertility may extend beyond gynecologic cancers. Thyroid cancers and melanomas deserve specific attention, particularly with respect to endometriosis.
authors.affiliation: National Cancer Institute, Rockville, Maryland 20852-7234, USA.
authors.forename: Louise A
authors.initials: LA
authors.lastname: Brinton
authors.forename: Carolyn L
authors.initials: CL
authors.lastname: Westhoff
authors.forename: Bert
authors.initials: B
authors.lastname: Scoccia
authors.forename: Emmet J
authors.initials: EJ
authors.lastname: Lamb
authors.forename: Michelle D
authors.initials: MD
authors.lastname: Althuis
authors.forename: Jerome E
authors.initials: JE
authors.lastname: Mabie
authors.forename: Kamran S
authors.initials: KS
authors.lastname: Moghissi
mesh_terms: D000328:Adult; D015984:Causality; D015331:Cohort Studies; D004715:Endometriosis / Q000150:complications; D005260:Female; D006801:Humans; D015994:Incidence; D007247:Infertility, Female / Q000453:epidemiology / Q000209:etiology*; D008875:Middle Aged; D009369:Neoplasms / Q000145:classification / Q000453:epidemiology*; D012042:Registries; D012189:Retrospective Studies; D018570:Risk Assessment; D012307:Risk Factors; D011795:Surveys and Questionnaires; D014481:United States / Q000453:epidemiology; D016387:Women's Health