The Ile646Val (2073A>G) Polymorphism in the Kinase-Binding Domain of A-Kinase Anchoring Protein 10 and the Risk of Colorectal Cancer

Abstract

Objective: The purpose of this study is to investigate whether the Ile646Val (2073A>G) polymorphism in the kinase-binding domain of A-kinase anchoring protein 10 (AKAP10) is related to the risk of colorectal cancer (CRC), clinicopathological variables and the environmental factors for the development of CRC. Methods: Applying TaqMan allelic discrimination, we investigated AKAP10 Ile646Val (2073A>G) polymorphism in 288 Chinese CRC patients and 281 healthy controls. Results: Logistic regression analysis revealed a significant association of AKAP10 Ile646Val (2073A>G) polymorphism with increased CRC risk (adjusted OR = 1.44, 95% CI 1.01–2.07, p = 0.02). Stratification analysis showed that the increased risk associated with the variant genotypes (GG+AG) was more evident in male subjects (adjusted OR = 1.48, 95% CI 0.94–2.34, p = 0.03). Compared with the AA genotype, the adjusted OR for the variant genotypes was 1.81 (95% CI 1.08–3.05, p = 0.01) among young subjects (age <57 years). Among individuals who did not smoke or who smoked lightly, there was a significantly increased risk with the variant genotypes (adjusted OR = 1.66, 95% CI 1.08–2.56, p = 0.02). We did not observe a relationship between the AKAP10 polymorphism and other clinicopathological and environmental factors. Conclusions: Our data suggested that the AKAP10 2073A>G variation is associated with an increased risk of CRC in the Chinese population.

A-Kinase Anchoring Proteins 10 Expression in Relation to 2073A/G Polymorphism and Tumor Progression in Patients with Colorectal Cancer

“…The studies of 787 familial breast cancer patients and 993 controls showed that the Ile646Val polymorphism of AKAP10 was associated with an increased familial breast cancer risk [12]. In a previous case-control study, we firstly found that the Ile646Val polymorphism of AKAP10 was significantly associated with colorectal cancer risk [13].…”

“…The TaqMan RT-PCR targeted for AKAP10 A-2073G polymorphism was performed according to previous description [13]. Primers and TaqMan probes were purchased from Invitrogen Biotechnology …”

“…Based on this critical study, we have conducted a case-control study in a Southwestern Chinese population and found that AKAP10 polymorphism (2073 A/G, I646V) was associated with colorectal cancer risk. The Chinese individuals with the G genotype might be linked with the increased risk of developing colorectal cancer [13]. However, the AKAP10 expression in human colorectal cancer and its role in the carcinogenesis as well as the relationships to the clinicopathologic factors remain unclear.…”

Gene Expression in Chronic Fatigue Syndrome

“…AKAP10 is the kinase-anchoring gene 10 which is currently an identifier for determining the risk of developing colorectal cancer (Wang et al, 2009a;Wang et al, 2009b). It also requires cAMP to diffuse through the cytoplasm to propagate its signal.…”

Possible counter effect in newborns of 1936A>G (I646V) polymorphism in the AKAP10 gene encoding A-kinase-anchoring protein 10

“…12 Subsequently, further studies confirmed the 'deleterious' effect of the G1936 variant with associations with familial breast cancer, 13 increased basal heart rate and decreased heart rate variability 14,15 and increased risk of colorectal cancer. 16 It is, therefore, presumed that biochemical changes, namely the V646 (G1936) AKAP10 binding of PKA RIa with threefold greater affinity than the I646 variant, and increased targeting of the PKA RIa subunit to the mitochondria result in the observed association of the G1936 allele with mortality and morbidity in the adult population. 12 Both alleles are sustained in the population; the G allele is found in up to 37% alleles in people of European descent (i.e., Aboriginal Europeans), is less common in Asian populations (E16 to 20%), but is the major allele in Africans (E58 to 72%).…”