Abstract 1858: Genetic variations in acid phosphatase 1 (ACP 1) gene and cancer risk
Authors: Andavolu Radhika G. , Cardenas Jean-Luc , Rubakovic Svetlana , Torabi Sina J. , Herling Patrick , MacMurray James , Andavolu Murthy V. 
Published: May 2015

BACKGROUND: Human acid phosphatases are normally found in low concentrations, but pronounced changes in their synthesis occur in particular diseases where unusually high or low enzyme expression is seen as part of the pathophysiological process,suggesting the clinical relevance of ACP as a disease marker. Acid Phosphatase 1 (ACP1) is considered to play a key role as a regulator of signaling pathways in receptor-stimulated immune cells and is known to be widely expressed and endowed with metabolic and proliferative activity. We hypothesized ACP1 could serve as a predictive marker in identifying cancer patients at an earlier stage, especially when disease is treatable. Acid phosphatase enzymes is generally correlated with the 3 co-dominant alleles A, B & C. This is the first study screening two ACP1 gene polymorphisms and ACP gene expressions in different cancer types. In this study, we exploit a novel connection of enzymatic activity in correlations to these two ACP1 polymorphisms and with more specific quantification of acid phosphatase in tumor tissues in primary and metastatic cancer patients.

METHODS: All study subjects were non-Hispanic Caucasians. The study sample was comprised of 661 cancer patients (221 breast; 121 prostate;137 malignant melanoma;196 other cancers) and 827 healthy controls. DNA & RNA was isolated from all cancer patients & controls using standard procedure.PCR-RFLP method was used. ACP1 alleles (i.e., ACP1*A, ACP1*B, and ACP1*C) were determined with 2 of the selected SNPs: rs11553742 (C&gt;T) is a synonymous polymorphism located in the codon 44 (exon 3) and rs7576247 (A/G) encodes an amino acid change in the codon 105 (exon 6) from arginine, present in ACP1*A allele, to glutamine in ACP1*B and *C alleles. Genotype and haplotype analysis was done using PASW 18 (SPSS IBM). qPCR is performed in tumor tissues and comparisons were made among cancer types and also in correlation with the haplotype based enzyme activity.

RESULTS: A very significant association of ACP haplotypes AA & AB with cancers is observed (p&lt;0.00001). Further analysis of these haplotypes in cancer types controlling for age and sex showed significant association mainly with Melanoma (p&lt;0.0001); prostate ca (p&lt;0.002); breast ca (p&lt;0.013) and all other cancers (p&lt; 0.002). Primary cases showed low activity while the metastatic cases showed high activity (&gt; 2fold). CONCLUSIONS:The enzymatic activity from gene combination correlates with the gene expression data. The primary cancer cases showed a low expression. Our data also shows an over expression of ACP1(&gt;2 fold) in metastatic cases as compared to the primary cases. This data supports the previous report on alkaline phosphatases (APs) catalyse and facilitate important physiological changes within cells and their expression is altered in many disease processes. It is clearly evident from this study that the ACP1 gene can be a critical marker in screening patients who are deemed low to high risk for cancer and metastasis.

Citation Format: Radhika G. Andavolu, Jean-Luc Cardenas, Svetlana Rubakovic, Sina J. Torabi, Patrick Herling, James MacMurray, Murthy VS Andavolu. Genetic variations in acid phosphatase 1 (ACP 1) gene and cancer risk. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 1858. doi:10.1158/1538-7445.AM2014-1858