Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1991 Apr;63(4):596–600. doi: 10.1038/bjc.1991.138

Is aryl hydrocarbon hydroxylase activity a new prognostic indicator for breast cancer?

K Pyykkö 1, R Tuimala 1, L Aalto 1, T Perkiö 1
PMCID: PMC1972352  PMID: 2021546

Abstract

Aryl hydrocarbon hydroxylase (AHH) activity was measured in the breast tumours of 153 primary and 17 recurrent cancer patients, and in 18 patients with benign breast tumour. All operations were carried out in 1983-84. The cytosolic fraction was collected for steroid receptor determination, and microsomes were separated for AHH assay from the same tissue samples. The AHH distribution was wide and highly skewed in all groups. About 10% of the samples showed activities below detection limit. The medians and ranges for primary cancers were 34 (less than 5-2683), for recurrent cancers 40 (20-239) and for benign tumours 11 (less than 5-37) fmol min-1 mg-1 protein. After logarithmic transformation, the mean AHH activities of cancer samples differed significantly from those of benign tumours. The logarithm of AHH activity (log AHH) correlates positively with axillary lymph node status, and negatively with steroid receptor levels. The development of the disease and the survival of the patients were followed for 4 years. The survival and the disease-free interval of the cancer patients who had low AHH activity was significantly higher than that of the high AHH group. The multivariate analysis with Cox's proportional hazad model showed primary tumour size, progesterone receptor concentration, nodal status and log AHH to be the most important independent prognostic factors for survival, while the occurrence of metastases, log AHH and tumour size were the equivalent factors for the disease-free interval in primary breast cancers. We conclude that AHH activity may reflect the overall malignant potential of breast cancer tissue.

Full text

PDF
596

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beahrs O. H. Staging of cancer of the breast as a guide to therapy. Cancer. 1984 Feb 1;53(3 Suppl):592–594. doi: 10.1002/1097-0142(19840201)53:3+<592::aid-cncr2820531303>3.0.co;2-9. [DOI] [PubMed] [Google Scholar]
  2. Carter C. L., Allen C., Henson D. E. Relation of tumor size, lymph node status, and survival in 24,740 breast cancer cases. Cancer. 1989 Jan 1;63(1):181–187. doi: 10.1002/1097-0142(19890101)63:1<181::aid-cncr2820630129>3.0.co;2-h. [DOI] [PubMed] [Google Scholar]
  3. Cohen G. M., Mehta R., Meredith-Brown M. Large interindividual variations in metabolism of benzo(alpha)pyrene by peripheral lung tissue from lung cancer patients. Int J Cancer. 1979 Aug;24(2):129–133. doi: 10.1002/ijc.2910240202. [DOI] [PubMed] [Google Scholar]
  4. Furr B. J., Jordan V. C. The pharmacology and clinical uses of tamoxifen. Pharmacol Ther. 1984;25(2):127–205. doi: 10.1016/0163-7258(84)90043-3. [DOI] [PubMed] [Google Scholar]
  5. Kellermann G., Luyten-Kellermann M., Shaw C. R. Genetic variation of aryl hydrocarbon hydroxylase in human lymphocytes. Am J Hum Genet. 1973 May;25(3):327–331. [PMC free article] [PubMed] [Google Scholar]
  6. Korenman S. G., Dukes B. A. Specific estrogen binding by the cytoplasm fof human breast carcinoma. J Clin Endocrinol Metab. 1970 May;30(5):639–645. doi: 10.1210/jcem-30-5-639. [DOI] [PubMed] [Google Scholar]
  7. Kouri R. E., McKinney C. E., Slomiany D. J., Snodgrass D. R., Wray N. P., McLemore T. L. Positive correlation between high aryl hydrocarbon hydroxylase activity and primary lung cancer as analyzed in cryopreserved lymphocytes. Cancer Res. 1982 Dec;42(12):5030–5037. [PubMed] [Google Scholar]
  8. Kärki N. T., Pokela R., Nuutinen L., Pelkonen O. Aryl hydrocarbon hydroxylase in lymphocytes and lung tissue from lung cancer patients and controls. Int J Cancer. 1987 May 15;39(5):565–570. doi: 10.1002/ijc.2910390505. [DOI] [PubMed] [Google Scholar]
  9. Levine A. S., McKinney C. E., Echelberger C. K., Kouri R. E., Edwards B. K., Nebert D. W. Aryl hydrocarbon hydroxylase inducibility among primary relatives of children with leukemia or solid tumors. Cancer Res. 1984 Jan;44(1):358–362. [PubMed] [Google Scholar]
  10. Lynch H. T., Albano W. A., Danes B. S., Layton M. A., Kimberling W. J., Lynch J. F., Cheng S. C., Costello K. A., Mulcahy G. M., Wagner C. A. Genetic predisposition to breast cancer. Cancer. 1984 Feb 1;53(3 Suppl):612–622. doi: 10.1002/1097-0142(19840201)53:3+<612::aid-cncr2820531306>3.0.co;2-5. [DOI] [PubMed] [Google Scholar]
  11. Mason M. E., Okey A. B. Aryl hydrocarbon hydroxylase activity in mouse, rat, and human mammary tumors. Cancer Res. 1981 Jul;41(7):2778–2782. [PubMed] [Google Scholar]
  12. Mettlin C. Diet and the epidemiology of human breast cancer. Cancer. 1984 Feb 1;53(3 Suppl):605–611. doi: 10.1002/1097-0142(19840201)53:3+<605::aid-cncr2820531305>3.0.co;2-0. [DOI] [PubMed] [Google Scholar]
  13. Nebert D. W., Gelboin H. V. Substrate-inducible microsomal aryl hydroxylase in mammalian cell culture. I. Assay and properties of induced enzyme. J Biol Chem. 1968 Dec 10;243(23):6242–6249. [PubMed] [Google Scholar]
  14. Nebert D. W., Gonzalez F. J. P450 genes: structure, evolution, and regulation. Annu Rev Biochem. 1987;56:945–993. doi: 10.1146/annurev.bi.56.070187.004501. [DOI] [PubMed] [Google Scholar]
  15. Pasanen M., Stacey S., Lykkesfeldt A., Briand P., Hines R., Autrup H. Induction of cytochrome P-450IA1 gene expression in human breast tumour cell lines. Chem Biol Interact. 1988;66(3-4):223–232. doi: 10.1016/0009-2797(88)90073-7. [DOI] [PubMed] [Google Scholar]
  16. Pasanen M., Stenbäck F., Park S. S., Gelboin H. V., Pelkonen O. Immunohistochemical detection of human placental cytochrome P-450-associated mono-oxygenase system inducible by maternal cigarette smoking. Placenta. 1988 May-Jun;9(3):267–275. doi: 10.1016/0143-4004(88)90034-3. [DOI] [PubMed] [Google Scholar]
  17. Pelkonen O., Nebert D. W. Metabolism of polycyclic aromatic hydrocarbons: etiologic role in carcinogenesis. Pharmacol Rev. 1982 Jun;34(2):189–222. [PubMed] [Google Scholar]
  18. Peterson G. L. A simplification of the protein assay method of Lowry et al. which is more generally applicable. Anal Biochem. 1977 Dec;83(2):346–356. doi: 10.1016/0003-2697(77)90043-4. [DOI] [PubMed] [Google Scholar]
  19. Roberts E. A., Golas C. L., Okey A. B. Ah receptor mediating induction of aryl hydrocarbon hydroxylase: detection in human lung by binding of 2,3,7,8-[3H]tetrachlorodibenzo-p-dioxin. Cancer Res. 1986 Jul;46(7):3739–3743. [PubMed] [Google Scholar]
  20. Robinson S. P., Jordan V. C. Metabolism of steroid-modifying anticancer agents. Pharmacol Ther. 1988;36(1):41–103. doi: 10.1016/0163-7258(88)90112-x. [DOI] [PubMed] [Google Scholar]
  21. Sabadie N., Richter-Reichhelm H. B., Saracci R., Mohr U., Bartsch H. Inter-individual differences in oxidative benzo(a)pyrene metabolism by normal and tumorous surgical lung specimens from 105 lung cancer patients. Int J Cancer. 1981;27(4):417–425. doi: 10.1002/ijc.2910270402. [DOI] [PubMed] [Google Scholar]
  22. Senler T. I., Dean W. L., Murray L. F., Wittliff J. L. Quantification of cytochrome P-450-dependent cyclohexane hydroxylase activity in normal and neoplastic reproductive tissues. Biochem J. 1985 Apr 15;227(2):379–387. doi: 10.1042/bj2270379. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Senler T. I., Hofmann G. E., Sanfilippo J. S., Barrows G. H., Dean W. L., Wittliff J. L. Cytochrome P-450 activity in human leiomyoma and normal myometrium. Am J Obstet Gynecol. 1985 Nov 1;153(5):551–555. doi: 10.1016/0002-9378(85)90471-5. [DOI] [PubMed] [Google Scholar]
  24. Thomas D. B. Do hormones cause breast cancer? Cancer. 1984 Feb 1;53(3 Suppl):595–604. doi: 10.1002/1097-0142(19840201)53:3+<595::aid-cncr2820531304>3.0.co;2-y. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES