Qualitative Age Interactions between Low-grade and High-grade Serous Ovarian Carcinomas

• Published in: Cancer epidemiology, biomarkers & prevention Vol. 18; no. 8; pp. 2256 - 2261
• Main Authors: GRIMLEY, Philip M, MATSUNO, Rayna K, ROSENBERG, Philip S, HENSON, Donald E, SCHWARTZ, Arnold M, ANDERSON, William F
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.08.2009
• Subjects: Adolescent; Adult; Age Distribution; Age Factors; age-period-cohort effects; age-specific incidence; Aged; Aged, 80 and over; Biological and medical sciences; carcinogenesis; Cystadenocarcinoma, Serous - epidemiology; Cystadenocarcinoma, Serous - pathology; early stage; Female; Female genital diseases; Gynecology. Andrology. Obstetrics; high grade; Humans; Incidence; incidence rate ratios; Kaplan-Meier Estimate; late stage; low grade; Medical sciences; Middle Aged; ovarian epithelial carcinoma; Ovarian Neoplasms - epidemiology; Ovarian Neoplasms - pathology; qualitative age interactions; SEER Program; serous ovarian carcinoma; subgroup analysis; Tumors; Young Adult; Ovary carcinoma; Ovary cancer; Interaction; Malignant tumor; Female genital diseases; High grade; Ovarian diseases; Cancerology; Serous carcinoma; Age; Cancer; Low grade; High malignancy
• ISSN: 1055-9965; 1538-7755
• DOI: 10.1158/1055-9965.EPI-09-0240

Purpose: 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 ≈ 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. (Cancer Epidemiol Biomarkers Prev 2009;18(8):2256–61)