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3'-UTR Polymorphisms in the MiRNA Machinery Genes DROSHA, DICER1, RAN, and XPO5 Are Associated with Colorectal Cancer Risk in a Korean Population.

Cho SH, Ko JJ, Kim JO, Jeon YJ, Yoo JK, Oh J, Oh D, Kim JW, Kim NK - PLoS ONE (2015)

Bottom Line: Stratified analysis revealed the RAN rs14035 combined CT+TT genotype was associated with decreased CRC risk in male patients without diabetes mellitus (DM) and in patients with rectal cancer.In addition, we found the RAN rs14035 CC genotype was related to a decreased risk of CRC with respect to tumor size and metabolism of homocysteine and folate.Our results indicate variations in RAN rs14035, DICER1 rs3742330, XPO5 rs11077, and DROSHA rs10719 of Korean patients are significantly associated with their risk of CRC.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea; Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.

ABSTRACT
MicroRNAs play an important role in cancer initiation and development. The aim of this study was to investigate whether polymorphisms in miRNA machinery genes are associated with the development of colorectal cancer (CRC). RAN rs14035 CT heterozygotes and T allele carriers (CT + TT) genotypes had lower risk of CRC, while the DICER1 rs3742330, DROSHA rs10719, and XPO5 rs11077 polymorphisms were not associated with CRC in the full study sample. Specifically, male RAN rs14035 CT heterozygotes and XPO5 rs11077 AA genotype (CT/AA) carriers experienced reduced CRC susceptibility (both colon and rectal). Subgroup analysis demonstrated that the combined RAN rs14035 CT + TT genotype was associated with rectal cancer, but not colon cancer. In addition, the DICER1 rs3742330 AG genotype was associated with a significantly increased risk of colon cancer. Stratified analysis revealed the RAN rs14035 combined CT+TT genotype was associated with decreased CRC risk in male patients without diabetes mellitus (DM) and in patients with rectal cancer. In addition, we found the RAN rs14035 CC genotype was related to a decreased risk of CRC with respect to tumor size and metabolism of homocysteine and folate. Furthermore, patients diagnosed with hypertension or DM who carried the DROSHA rs10719 CC genotype showed increased CRC risk, while the XPO5 rs11077 AC+CC genotype led to increased CRC risk in patients with hypertension only. Our results indicate variations in RAN rs14035, DICER1 rs3742330, XPO5 rs11077, and DROSHA rs10719 of Korean patients are significantly associated with their risk of CRC.

No MeSH data available.


Related in: MedlinePlus

The effects of DROSHA rs10719T>C variant on colorectal cancer (CRC) development modulated by diabetes mellitus (DM).Y-axis represents fold changes between DROSHA genotype TT+TC and DROSHA genotype CC. Each row represents the patients with or without DM. Each column represents DROSHA genotype TT+TC and DROSHA genotype CC.
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pone.0131125.g001: The effects of DROSHA rs10719T>C variant on colorectal cancer (CRC) development modulated by diabetes mellitus (DM).Y-axis represents fold changes between DROSHA genotype TT+TC and DROSHA genotype CC. Each row represents the patients with or without DM. Each column represents DROSHA genotype TT+TC and DROSHA genotype CC.

Mentions: We examined the potential genetic association between HTN or DM and gene/patient characteristics to elucidate the genetic etiology of CRC development because metabolic syndrome risk factors, including HTN and DM, are very relevant in the occurrence of CRC. We determined the DROSHA rs10719 CC genotype was associated increased risk of colon cancer in subjects 62 years or older (AOR = 3.875; 95% CI, 1.432–10.490) and patients with HTN (AOR, 3.292; 95% CI, 1.362–7.958), DM (AOR = 6.764; 95% CI, 1.424–32.126) (Table 8). Interestingly, the combination of DM and the DROSHA rs10719 CC genotype increased CRC risk 6.764-fold (Fig 1). We also observed an association between the XPO5 rs11077 combined AC+CC genotype and increased CRC risk in patients with HTN (AOR, 3.126; 95% CI, 1.739–5.619) or BMI of < 25 kg/m2 (AOR = 11.765; 95% CI, 1.011–3.079) (Table 8).


3'-UTR Polymorphisms in the MiRNA Machinery Genes DROSHA, DICER1, RAN, and XPO5 Are Associated with Colorectal Cancer Risk in a Korean Population.

Cho SH, Ko JJ, Kim JO, Jeon YJ, Yoo JK, Oh J, Oh D, Kim JW, Kim NK - PLoS ONE (2015)

The effects of DROSHA rs10719T>C variant on colorectal cancer (CRC) development modulated by diabetes mellitus (DM).Y-axis represents fold changes between DROSHA genotype TT+TC and DROSHA genotype CC. Each row represents the patients with or without DM. Each column represents DROSHA genotype TT+TC and DROSHA genotype CC.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4492935&req=5

pone.0131125.g001: The effects of DROSHA rs10719T>C variant on colorectal cancer (CRC) development modulated by diabetes mellitus (DM).Y-axis represents fold changes between DROSHA genotype TT+TC and DROSHA genotype CC. Each row represents the patients with or without DM. Each column represents DROSHA genotype TT+TC and DROSHA genotype CC.
Mentions: We examined the potential genetic association between HTN or DM and gene/patient characteristics to elucidate the genetic etiology of CRC development because metabolic syndrome risk factors, including HTN and DM, are very relevant in the occurrence of CRC. We determined the DROSHA rs10719 CC genotype was associated increased risk of colon cancer in subjects 62 years or older (AOR = 3.875; 95% CI, 1.432–10.490) and patients with HTN (AOR, 3.292; 95% CI, 1.362–7.958), DM (AOR = 6.764; 95% CI, 1.424–32.126) (Table 8). Interestingly, the combination of DM and the DROSHA rs10719 CC genotype increased CRC risk 6.764-fold (Fig 1). We also observed an association between the XPO5 rs11077 combined AC+CC genotype and increased CRC risk in patients with HTN (AOR, 3.126; 95% CI, 1.739–5.619) or BMI of < 25 kg/m2 (AOR = 11.765; 95% CI, 1.011–3.079) (Table 8).

Bottom Line: Stratified analysis revealed the RAN rs14035 combined CT+TT genotype was associated with decreased CRC risk in male patients without diabetes mellitus (DM) and in patients with rectal cancer.In addition, we found the RAN rs14035 CC genotype was related to a decreased risk of CRC with respect to tumor size and metabolism of homocysteine and folate.Our results indicate variations in RAN rs14035, DICER1 rs3742330, XPO5 rs11077, and DROSHA rs10719 of Korean patients are significantly associated with their risk of CRC.

View Article: PubMed Central - PubMed

Affiliation: Department of Biomedical Science, College of Life Science, CHA University, Seongnam, South Korea; Institute for Clinical Research, CHA Bundang Medical Center, CHA University, Seongnam, South Korea.

ABSTRACT
MicroRNAs play an important role in cancer initiation and development. The aim of this study was to investigate whether polymorphisms in miRNA machinery genes are associated with the development of colorectal cancer (CRC). RAN rs14035 CT heterozygotes and T allele carriers (CT + TT) genotypes had lower risk of CRC, while the DICER1 rs3742330, DROSHA rs10719, and XPO5 rs11077 polymorphisms were not associated with CRC in the full study sample. Specifically, male RAN rs14035 CT heterozygotes and XPO5 rs11077 AA genotype (CT/AA) carriers experienced reduced CRC susceptibility (both colon and rectal). Subgroup analysis demonstrated that the combined RAN rs14035 CT + TT genotype was associated with rectal cancer, but not colon cancer. In addition, the DICER1 rs3742330 AG genotype was associated with a significantly increased risk of colon cancer. Stratified analysis revealed the RAN rs14035 combined CT+TT genotype was associated with decreased CRC risk in male patients without diabetes mellitus (DM) and in patients with rectal cancer. In addition, we found the RAN rs14035 CC genotype was related to a decreased risk of CRC with respect to tumor size and metabolism of homocysteine and folate. Furthermore, patients diagnosed with hypertension or DM who carried the DROSHA rs10719 CC genotype showed increased CRC risk, while the XPO5 rs11077 AC+CC genotype led to increased CRC risk in patients with hypertension only. Our results indicate variations in RAN rs14035, DICER1 rs3742330, XPO5 rs11077, and DROSHA rs10719 of Korean patients are significantly associated with their risk of CRC.

No MeSH data available.


Related in: MedlinePlus