Study of Serum Lactate Dehydrogenase and Gamma-Glutamyl Transpeptidase in Breast Cancer Patients receiving Chemotherapy.

Anil Singh Basnyat, Abimanyu Jha, R Pathak, Bhupal Govinda Shrestha

Abstract


Breast cancer (BC) is the most common type of cancer worldwide, being a major cause of morbidity in female. In Nepal it is the second most common type of cancer among females of perimenopausal age group. More than one quarter of the BC diagnosed in young Nepalese female, with familial history of breast cancer, early pregnancy, longer lactation and estrogen exposure and often with tumors showing aggressive biological behaviors. Anthracyclines (Doxorubicin) based treatment regime were reported to cause cardiotoxicity by increasing intramyocardial free radical production, lipid alterations and decreasing antioxidant level. Oxidative stress involving cellular reactive oxygen species (ROS) production is widely accepted mechanism but the molecular basis of chemotherapy induced organ toxicity remains highly controversial. An increased rate of metabolism and oxidative stress results rapid turnover of cancer cells that modulates the enzyme level in blood circulation. Serum LDH and GGT level correlates with tumor burden, metastatic character of BC and intensity of organtoxicity. The aim of our study is to evaluate the serum level of LDH and GGT in BC patients receiving chemotherapy and correlate these enzyme levels with different stages of BC. A total number of 150 subjects were included in the study, comprising 90 histopathologically confirmed 24 to 76 years aged patients of different breast cancer stages, receiving at least 3 cycles of 5-Fluorouracil, Adriamycin and Cyclophosphamide (FAC) chemotherapy. Sixty age- matched healthy women were enrolled as controls. Blood samples from each individual was collected after informed consent and analysed for serum LDH and GGT levels using standard biochemical methods. Data were analyzed using student's paired 't' test, Pearson correlation test and ANOVA. Serum LDH and GGT levels were significantly (p<0.001) increased in BC patients as compared to control group. When all 4 stages of BC were compared to control group, LDH and GGT showed steady and progressive increase in the activities of these enzymes from stage I-IV. The study concludes that serum LDH and GGT may be sensitive, specific and cost effective biomarkers in early diagnosis of breast cancer, assessing cancer prognosis and response to treatment.


Keywords


Breast cancer; stages; chemotherapy; Lactate dehydrogenase;Gamma glutamyl transpeptidase

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References


World Health Organization (2016) Breast cancer: prevention and control. http://www.who.int/. Accessed: September 2016.

World Cancer Research Fund International (2016) Breast cancer statistics. http://www.wcrf.org/. Accessed: September 2016.

World Health Organization (2013) Global Health Estimates 2013. Accessed: September 2016.

Singh YP, Sayami P (2009) Management of breast cancer in Nepal. Journal of Nepal Medical Association 48 (175): 252-257.

Thapa B, Singh YP, Sayami P et al. (2013) Breast cancer in young women from a low risk population in Nepal. Asian Pacific Journal of Cancer Prevention 14 (9): 5095-5099.

Cao R, Wang LP (2012) Serological diagnosis of liver metastasis in patients with breast cancer. Cancer Biology and Medicine 9 (1): 57-62.

Bogdanovic V, Tursijan S, Dordevic M et al. (2008) Activity of lactate dehydrogenase and superoxide dismutase in the circulation of patients with breast carcinoma. Archive of Oncology 16 (3-4): 39-41.

EI Maksoud NA, Samy N, Ragab HM, Shaalan M (2009) Clinical significance of antioxidants, lactate dehydrogenase and alkaline phophatase in breast cancer patients with and without lymph node metastases. Journal of Genetic Engineering and Biotechnology 7 (2): 59-64.

Grimm C, Hofstetter G, Aust S et al. (2013) Association of gamma-glutamyltransferase with severity of disease at diagnosis and prognosis of ovarian cancer. British Journal of Cancer 109: 610-614.

Pompella A, Tata VD, Paolicchi A, Zunino F (2006) Expression of γ-gutamyltransferase in cancer cells and its significance in drug resistance. Biochemical Pharmacology 71: 231-238.

Amin KA, Mohamed BM, El-wakil MAM, Ibrahem SO (2012) Impact of breast cancer and combination chemother

apy on oxidative stress, hepatic and cardiac markers. Journal of Breast Cancer 15 (3): 306-312.

Kaithwas G, Dubey K, Pillai KK (2011) Effect of aloe vera (Aloe barbadenis Miller) gel on doxorubicin-induced myocardial oxidative stress and calcium overload in albino rats. Indian Journal of Experimental Biology 49: 260-268.

Jarari AM, Shakila S, Alsoaeitiv SO et al. (2013) Serum levels of LDH and gamma GT in Libyan breast cancer patients. Indian Journal of Applied Research 3 (12): 32-34.

Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19 (5): 403-410. doi: 10.1111/j.1365-2559.1991.tb00229.x

Choudhari A, Desai P, Indumati V, Kadi S (2013) Activities of serum ADA, GGT and ALP in carcinoma breast- a case control study for diagnostic and prognostic significance. Indian Journal of Medical Sciences 67 (5): 123-128.

Chandrakanth KH, Nagaraj, Jayaprakash MDS et al. (2011) Study of serum levels of Gamma-glutamyl transferase, lactate dehydrogenase, malondialdehyde and vitamin-E in breast cancer. International Journal of Pharma and Bio Sciences 2 (4): B489-B498.

Guddanti R, Srinivas PS, Sai SRK, Eadala S (2016) Study of serum LDH and GGT levels in carcinoma breast. International Journal of Biomedical and Advance Research 7 (1): 31-34.

Koukourakis M, Kontomanolis E, Giatromanolaki A et al. (2009) Serum and tissue LDH in patients with breast/gynaecological cancer and benign diseases. Gynecologic and Obstetric Investigation 67 (3): 162-168.

Basnyat AS, Gyawali P, Jha A et al. (2016) Evaluation of Serum Lipids and C-peptide among Breast Cancer Patients with Chemotherapy. Annals of Clinical Chemistry and Laboratory Medicine 2 (2): 8-14.

Strasak AM, Pfeiffer RM, Klenk J et al. (2008) Prospective study of the association of gamma-glutamyltransferase with cancer. International Journal of Cancer 123 (8): 1902-1906. doi: 10.1002/ijc.23714

Fentiman IS, Allen DS (2010) γ-Glutamyltransferase and breast cancer risk. British Journal of Cancer 103: 90-93. doi: 10.1038/sj.bjc.6605719.

Staudigl C, Concin N, Grimm C et al. (2015) Prognostic relevance of pretherapeutic Gamma-glutamyltransferase in patients with primary metastatic breast cancer. PlosOne 10 (4): 1-10.




DOI: http://dx.doi.org/10.11594/jtls.07.02.07

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