title: Prospective study of the association of serum gamma-glutamyltransferase with cervical intraepithelial neoplasia III and invasive cervical cancer.
abstract: 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.
authors.affiliation: Departments of Medical Statistics, Innsbruck Medical University, Innsbruck, Austria.
authors.forename: Alexander M
authors.initials: AM
authors.lastname: Strasak
authors.forename: Georg
authors.initials: G
authors.lastname: Goebel
authors.forename: Hans
authors.initials: H
authors.lastname: Concin
authors.forename: Ruth M
authors.initials: RM
authors.lastname: Pfeiffer
authors.forename: Larry J
authors.initials: LJ
authors.lastname: Brant
authors.forename: Gabriele
authors.initials: G
authors.lastname: Nagel
authors.forename: Willi
authors.initials: W
authors.lastname: Oberaigner
authors.forename: Nicole
authors.initials: N
authors.lastname: Concin
authors.forename: Günter
authors.initials: G
authors.lastname: Diem
authors.forename: Elfriede
authors.initials: E
authors.lastname: Ruttmann
authors.forename: Ulrike
authors.initials: U
authors.lastname: Gruber-Moesenbacher
authors.forename: Felix
authors.initials: F
authors.lastname: Offner
authors.forename: Alfonso
authors.initials: A
authors.lastname: Pompella
authors.forename: Karl P
authors.initials: KP
authors.lastname: Pfeiffer
authors.forename: Hanno
authors.initials: H
authors.lastname: Ulmer
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001317:Austria / Q000453:epidemiology; D015331:Cohort Studies; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D015994:Incidence; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D011446:Prospective Studies; D012307:Risk Factors; D002583:Uterine Cervical Neoplasms / Q000201:enzymology* / Q000453:epidemiology / Q000473:pathology; D055815:Young Adult; D005723:gamma-Glutamyltransferase / Q000097:blood*; D002578:Uterine Cervical Dysplasia / Q000201:enzymology* / Q000453:epidemiology / Q000473:pathology
chemical_list: D005723:gamma-Glutamyltransferase
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