PMC:3492652 / 9840-13045 JSONTXT

{"target":"https://pubannotation.org/docs/sourcedb/PMC/sourceid/3492652","sourcedb":"PMC","sourceid":"3492652","source_url":"https://www.ncbi.nlm.nih.gov/pmc/3492652","text":"Discussion\nV-akt murine thymoma viral oncogene homolog (AKT) is a serine/threonine protein kinase that is activated by PI3K-α and mediates PI3L signaling [21]. A major recurrent mutation (Glu17Lys) in the AKT1 gene, which encodes protein kinase B, has been identified in several solid tumors, including breast, colon, and ovarian cancers [22]. Overall, the frequency of AKT1 mutations in non-small cell lung carcinoma (NSCLC) is about 1%, and they have only been identified in squamous cell carcinoma [23]. Also, mutations in the AKT2 and AKT3 genes are rare in several tumors, including lung cancer [15].\nRecently, several polymorphisms in the AKT1 gene have been reported in relation to human disease [24-26]. Kim et al. [20] first reported that the AKT1 polymorphisms could be used as prognostic markers for patients with early-stage NSCLC. However, there has been no study on the association between lung cancer risk and polymorphisms of AKT2 and AKT3. In this study, we investigated the association between AKT2 and AKT3 polymorphisms and the risk of lung cancer in the Korean population. The genotypes and haplotypes of the AKT2 and AKT3 genes were determined in 720 Koreans to evaluate the role of the AKT2 and AKT3 polymorphisms in the risk of lung cancer; however, the results revealed no significant difference between lung cancer patients and normal controls. Also, by TFSEARCH (version 1.3) analysis of the AKT2 and AKT3 polymorphism regions, the location of these variants did not have sequences for transcription factor binding sites. This result suggests that polymorphisms of the AKT2 and AKT3 promoter region are unlikely to play an important role in the susceptibility to lung cancer.\nPolymorphisms often show ethnic variation [6, 27]. In the present study, we observed the frequencies of 5 polymorphisms in the AKT2 promoter region, and we observed frequencies of 3 polymorphisms in the AKT3 promoter region in 24 Korean populations using direct sequencing. In the direct sequencing result, we detected no frequencies in another known polymorphisms (AKT2: rs11666690, rs11665880, rs35814223, rs34408497, rs35408040, rs10418387; AKT3: rs11588441, rs6679386, rs41267521). The frequencies of AKT2 promoter polymorphisms showed similar frequencies in the Asian ethnic groups (Han Chinese and Japanese) of the dbSNP database (www.ncbi.nlm.nih.gov/SNP). The frequency of the minor allele of rs35835614 in the AKT3 gene was 0.275; however, the frequency of this polymorphism has not been reported in the dbSNP database (www.ncbi.nlm.nih.gov/SNP). A series of our previous studies showed that polymorphisms of oncogenes, tumor suppressor genes, and receptor tyrosine kinases are related to lung cancer risk [6, 28, 29]. Recently, we reported that STK11 and PIK3CA polymorphisms are not related to genetic susceptibility to lung cancer [30, 31]. The genotypes of the AKT2 and AKT3 promoter polymorphisms, determined in 720 Koreans in the present study, revealed no significant difference between lung cancer patients and normal controls. To our best knowledge, this is the first study on the association of AKT2 and AKT3 promoter polymorphisms and the risk of lung cancer in a Korean population.","divisions":[{"label":"Title","span":{"begin":0,"end":10}}],"tracks":[{"project":"2_test","denotations":[{"id":"23166527-11572954-44844445","span":{"begin":155,"end":157},"obj":"11572954"},{"id":"23166527-17611497-44844446","span":{"begin":339,"end":341},"obj":"17611497"},{"id":"23166527-18256540-44844447","span":{"begin":502,"end":504},"obj":"18256540"},{"id":"23166527-17047397-44844448","span":{"begin":601,"end":603},"obj":"17047397"},{"id":"23166527-16260726-44844449","span":{"begin":704,"end":706},"obj":"16260726"},{"id":"23166527-18838251-44844449","span":{"begin":704,"end":706},"obj":"18838251"},{"id":"23166527-15522255-44844449","span":{"begin":704,"end":706},"obj":"15522255"},{"id":"23166527-21842521-44844450","span":{"begin":724,"end":726},"obj":"21842521"},{"id":"23166527-18313166-44844451","span":{"begin":1746,"end":1747},"obj":"18313166"},{"id":"23166527-16497724-44844452","span":{"begin":1749,"end":1751},"obj":"16497724"},{"id":"23166527-18313166-44844453","span":{"begin":2719,"end":2720},"obj":"18313166"},{"id":"23166527-19055823-44844454","span":{"begin":2722,"end":2724},"obj":"19055823"},{"id":"23166527-19343042-44844455","span":{"begin":2726,"end":2728},"obj":"19343042"},{"id":"23166527-20057966-44844456","span":{"begin":2851,"end":2853},"obj":"20057966"}],"attributes":[{"subj":"23166527-11572954-44844445","pred":"source","obj":"2_test"},{"subj":"23166527-17611497-44844446","pred":"source","obj":"2_test"},{"subj":"23166527-18256540-44844447","pred":"source","obj":"2_test"},{"subj":"23166527-17047397-44844448","pred":"source","obj":"2_test"},{"subj":"23166527-16260726-44844449","pred":"source","obj":"2_test"},{"subj":"23166527-18838251-44844449","pred":"source","obj":"2_test"},{"subj":"23166527-15522255-44844449","pred":"source","obj":"2_test"},{"subj":"23166527-21842521-44844450","pred":"source","obj":"2_test"},{"subj":"23166527-18313166-44844451","pred":"source","obj":"2_test"},{"subj":"23166527-16497724-44844452","pred":"source","obj":"2_test"},{"subj":"23166527-18313166-44844453","pred":"source","obj":"2_test"},{"subj":"23166527-19055823-44844454","pred":"source","obj":"2_test"},{"subj":"23166527-19343042-44844455","pred":"source","obj":"2_test"},{"subj":"23166527-20057966-44844456","pred":"source","obj":"2_test"}]}],"config":{"attribute types":[{"pred":"source","value type":"selection","values":[{"id":"2_test","color":"#93ec97","default":true}]}]}}