title: Qualitative age interactions between low-grade and high-grade serous ovarian carcinomas.
abstract: OBJECTIVE
  Ovarian epithelial carcinomas, including the predominant serous ovarian carcinoma (SOC) type, are heterogeneous malignancies. Even though invasive SOCs of low and high grade can be distinguished by morphology and molecular or immunohistochemical profiles, age-specific risks relevant to their separate carcinogenic pathways and clinical features have not been fully explored.
  
  
  METHODS
  In search of further clues to the etiology/pathogenesis of low-grade and high-grade SOCs, we analyzed incidence rate patterns. Case and age-adjusted population data were obtained from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) program for years 1990 through 2005. Descriptive epidemiology for n = 19,899 cases was supplemented with age-period-cohort models fitted by grade.
  
  
  RESULTS
  SOC age-adjusted incidence rate ratios (IRR) of high to low grade (IRR(H/L)) were <1.0 before age 40, and >1.0 thereafter. Accordingly, SOC age-specific incidence rates were also greater for low grade before age 40 years, and then greater for high grade. The reversals of IRR(H/L), with crossings of the age-specific incidence rate near age 40 years occurred irrespective of early or late SOC stage. These results were reproducible and reliable in age-period-cohort models that were adjusted for period and cohort effects (P approximately 0 for age interactions by grade).
  
  
  CONCLUSIONS
  Robust qualitative age interactions between low-grade and high-grade SOC showed that grade is an age-specific effect modifier in these malignancies. With increasing research interest in identifying the genomic determinants of SOC risk, therapeutic response, and outcome, future analytic studies and clinical trials should be powered to account for age-dependent grade interactions.
authors.affiliation: Department of Pathology, F. Edward Hébert School of Medicine, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA. pgrimley@usuhs.mil.
authors.forename: Philip M
authors.initials: PM
authors.lastname: Grimley
authors.forename: Rayna K
authors.initials: RK
authors.lastname: Matsuno
authors.forename: Philip S
authors.initials: PS
authors.lastname: Rosenberg
authors.forename: Donald E
authors.initials: DE
authors.lastname: Henson
authors.forename: Arnold M
authors.initials: AM
authors.lastname: Schwartz
authors.forename: William F
authors.initials: WF
authors.lastname: Anderson
mesh_terms: D000293:Adolescent; D000328:Adult; D017677:Age Distribution; D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D018284:Cystadenocarcinoma, Serous / Q000453:epidemiology* / Q000473:pathology*; D005260:Female; D006801:Humans; D015994:Incidence; D053208:Kaplan-Meier Estimate; D008875:Middle Aged; D010051:Ovarian Neoplasms / Q000453:epidemiology* / Q000473:pathology*; D018426:SEER Program; D055815:Young Adult