Association of glutamate carboxypeptidase II (GCPII) haplotypes with breast and prostate cancer risk
| Autor: | Ch. Ram Reddy, Anthony Addlagatta, Shaik Mohammad Naushad, Shree Divyya, Raghunadharao Digumarti, Sreedhar Amere Subbarao, Vijay Kumar Kutala, Suryanarayana Raju Gottumukkala, P.V.L.N. Murthy |
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| Rok vydání: | 2012 |
| Předmět: |
Adult
Glutamate Carboxypeptidase II Male medicine.medical_specialty Protein Conformation In silico Breast Neoplasms Biology medicine.disease_cause Prostate cancer Young Adult Breast cancer Folic Acid Prostate Risk Factors Internal medicine Genetics medicine Glutamate carboxypeptidase II Humans Aged Prostate cancer risk Haplotype Prostatic Neoplasms General Medicine Middle Aged medicine.disease Gene Expression Regulation Neoplastic Endocrinology medicine.anatomical_structure Haplotypes Case-Control Studies Antigens Surface Cancer research Female Carcinogenesis |
| Zdroj: | Gene. 516(1) |
| ISSN: | 1879-0038 |
| Popis: | In view of the pivotal role of glutamate carboxypeptidase II (GCPII) in carcinogenesis, its expression as prostate specific membrane antigen (PSMA) and folate hydrolase (FOLH1) may be influenced by its haplotypes, contributing to the etiology of prostate and breast cancer. To test this hypothesis, breast and prostate cancer cases and controls were subjected to whole gene screening of GCPII and correlated with plasma folate levels and PSMA expression. The impact of variants on a 3-dimensional structure of GCPII was explored by in silico studies. Six novel variations i.e. V108A, P160S, Y176H, D191V, G206R and G245S; and two known variations i.e. R190W and H475Y were identified in GCPII. All-wild haplotype and a haplotype harbouring D191V showed association with breast cancer risk while haplotypes harbouring V108A and P160S reduced the risk. Haplotypes with V108A and G245S variants showed increased risk for prostate cancer due to high PSMA expression while P160S conferred protection against prostate cancer. In silico studies suggests that P160S and R190W variants result in relaxed substrate binding facilitating either rapid catalysis or exchange of substrates and products in the active site which was substantiated by high plasma folate levels associated with these variants. On the contrary, D191V was associated with very low plasma folate levels despite having a high PSMA expression. This is the first comprehensive study examining variations in GCPII in relation to breast and prostate cancer risk. Changes in the plasma folate levels and changes in PSMA expression are associated with breast and prostate cancer risk respectively. |
| Databáze: | OpenAIRE |
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