Most patients with epithelial ovarian cancer, the predominant form, are asymptomatic in early-stage disease and usually present with invasive stage III or IV disease. Their five-year survival is less than 25%, with lower survival among African American women. Difference in age-adjusted incidence and survival rates of ovarian cancer between African American and Caucasian women is substantial. The reason for this disparity is not known. There is a pressing need to identify accurate genetic predictive factors in ovarian cancer subtypes and stages to improve survival rates especially among minority women. The objective of this study was to examine mtDNA sequence variants in 136 frozen tissues of three subtypes of epithelial ovarian cancer (serous, n=48 endometrioid, n=47 and mucinous, n =23; matched paracancerous normal tissues, n= 18) in relation to ethnic and age differences. Two regions of mtDNA which spanned 5317 to 7608 and 8282 to 10110 bp, including ND subunits 2, 3,COXI, II, III, ATPase 8, a part of ATPase 6, and tRNA genes in 136 frozen tissues of ovarian cancer were evaluated. Thirty-nine variants were detected of which 28 were unreported. Variants C7256T and G7520A showed a frequency of 54% (6/11) in endometrioid stage III and no correspondence of the variants were observed in mucinous subtype stage III. Furthermore, variants C7256T and G7520A were absent in serous ovarian cancer subtype. Interestingly, C7520T variant in tRNA gene occurred at 74% (36/49) in African American and 26% (23/87) Caucasian among studied patients. A variant T8548G in ATP6 gene was detected at a frequency of 72% (18/25) in ovarian serous subtype tissues in stages III/IV. African American patients under the age 40 were found to harbor 95% (20/21) of the T8548G variant compare to Caucasian patients with 22% (8/35) of same age groups. A variant C7028T in MT-CO1 gene that was observed with appreciably ascending frequency from borderline (8%) to stages III/IV (75%) among the three ovarian cancer subtypes and stages, was found in 86% (42/49) of African-American and 43% (37/87) Caucasian women among our studied patients. Results suggest that the pathogenic roles of these observed variants are substantial in ovarian carcinogenesis in respect to ethnic and age difference. The analysis of other genes in the mtDNA genome could reveal higher difference in age-adjusted incidence of ovarian cancer between African American and Caucasian women.

Citation Information: In: Proc Am Assoc Cancer Res; 2009 Apr 18-22; Denver, CO. Philadelphia (PA): AACR; 2009. Abstract nr 1585.

100th AACR Annual Meeting-- Apr 18-22, 2009; Denver, CO

American Association for Cancer Research
2009