Prospective Study of the Association of Serum γ-Glutamyltransferase with Cervical Intraepithelial Neoplasia III and Invasive Cervical Cancer

• Published in: Cancer research (Chicago, Ill.) Vol. 70; no. 9; pp. 3586 - 3593
• Main Authors: STRASAK, Alexander M, GOEBEL, Georg, GRUBER-MOESENBACHER, Ulrike, OFFNER, Felix, POMPELLA, Alfonso, PFEIFFER, Karl P, ULMER, Hanno, CONCIN, Hans, PFEIFFER, Ruth M, BRANT, Larry J, NAGEL, Gabriele, OBERAIGNER, Willi, CONCIN, Nicole, DIEM, Günter, RUTTMANN, Elfriede
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Association for Cancer Research 01.05.2010
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic agents; Austria - epidemiology; Biological and medical sciences; Cervical Intraepithelial Neoplasia - enzymology; Cervical Intraepithelial Neoplasia - epidemiology; Cervical Intraepithelial Neoplasia - pathology; Cohort Studies; Female; Female genital diseases; Follow-Up Studies; gamma-Glutamyltransferase - blood; Gynecology. Andrology. Obstetrics; Humans; Incidence; Medical sciences; Middle Aged; Neoplasm Invasiveness; Pharmacology. Drug treatments; Prospective Studies; Risk Factors; Tumors; Uterine Cervical Neoplasms - enzymology; Uterine Cervical Neoplasms - epidemiology; Uterine Cervical Neoplasms - pathology; Young Adult; Austria; Acyltransferases; Biological fluid; Premalignant lesion; Enzyme; Transferases; Malignant tumor; Uterine cervix; Aminoacyltransferases; Female genital diseases; γ-Glutamyltransferase; Prospective; Cervical dysplasia; Cervical intraepithelial neoplasia; Serum; Invasive cancer; Uterine cervix diseases; Cervical cancer; Cancer
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-09-3197

Epidemiologic studies indicate that elevated levels of gamma-glutamyltransferase (GGT), a key enzyme of glutathione metabolism, might be associated with increased cancer risk. Furthermore, preclinical studies support a role for GGT in tumor invasion and progression. However, the relationship between GGT and risks of cervical intraepithelial neoplasia III (CIN-III) and invasive cervical cancer (ICC) have not been evaluated. We investigated the association of enzymatically determined GGT in blood serum with subsequent incidence of CIN-III and ICC in a prospective population-based cohort of 92,843 women ages 18 to 95, of whom 79% had at least one gynecologic examination including Pap smear testing during follow-up. Cox regression was used to compute adjusted hazard ratios (HR) with 95% confidence intervals for the association of GGT with CIN-III and ICC. During median follow-up of 13.8 years, 702 CIN-III and 117 ICC diagnoses were observed. Compared with normal low GGT (<17.99 units/L), risk of ICC was significantly elevated for all other baseline GGT categories, with adjusted HRs of 2.31 (1.49-3.59) for normal high GGT (18.00-35.99 units/L), 2.76 (1.52-5.02) for elevated GGT (36.00-71.99 units/L), and 3.38 (1.63-7.00) for highly elevated GGT [>72.00 units/L; P trend < 0.0001, HR log unit increase 3.45 (1.92-6.19)]. In contrast, associations between GGT serum levels and CIN-III risk were not statistically significant in the main analysis. Exclusion of the first 2 or 5 years of follow-up did not change the results. Effects did not differ by age, body mass index, or socioeconomic status. Our findings implicate GGT in the progression of premalignant cervical lesions to invasive cancer.