A copy number variation in PKD1L2 is associated with colorectal cancer predisposition in korean population.
Recently reported genome-wide association studies have identified more than 20 common low-penetrance colorectal cancer (CRC) susceptibility loci. Recent studies have reported that copy number variations (CNVs) are considered important human genomic variants related to cancer, while the contribution of CNVs remains unclear. We performed array comparative genomic hybridization (aCGH) in 36 CRC patients and 47 controls. Using breakpoint PCR, we confirmed the breakpoint of the PKD1L2 deletion region. High frequency of PKD1L2 CNV was observed in CRC cases. We validated the association between PKD1L2 variation and CRC risk in 1,874 cases and 2,088 controls (OR = 1.44, 95% CI = 1.04-1.98, p = 0.028). Additionally, PKD1L2 CNV is associated with increased CRC risk in patients younger than 50 years (OR = 2.14, 95% CI 1.39-3.30, p = 5.8 × 10-4). In subgroup analysis according to body mass index (BMI), we found that the CN loss of PKD1L2 with BMI above or equal to 25 exhibited a significant increase in CRC risk (OR = 2.29, 95% CI 1.29-4.05, p = 0.005). PKD1L2 CNV with BMI above or equal to 25 and age below 50 is associated with a remarkably increased risk of colorectal cancer (OR = 5.24, 95% CI 2.36-11.64, p= 4.8 × 10-5). Moreover, we found that PKD1L2 variation in obese patients (BMI ≥ 25) was associated with poor survival rate (p = 0.026). Our results suggest that the common PKD1L2 CNV is associated with CRC, and PKD1L2 CNV with high BMI and/or age below 50 exhibited a significant increased risk of CRC. In obese patients, PKD1L2 variation was associated with poor survival.
Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.|Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea.
Changho
C
Park
Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.|Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea.|Medical Research Center, Genomic Medicine Institute (GMI), Seoul National University, Seoul, Korea.|Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
Jong-Il
JI
Kim
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Sung Noh
SN
Hong
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Hey Mi
HM
Jung
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Tae Jun
TJ
Kim
Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.|Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea.|Medical Research Center, Genomic Medicine Institute (GMI), Seoul National University, Seoul, Korea.
Seungbok
S
Lee
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Seong Jin
SJ
Kim
Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Hee Cheol
HC
Kim
Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Suwon, Korea.
Duk-Hwan
DH
Kim
Department of Family Medicine, Seoul National University College of Medicine, Seoul, Korea.
Belong
B
Cho
Department of Family Medicine, Seoul National University College of Medicine, Seoul, Korea.
Jin-Ho
JH
Park
Complex Disease and Genome Epidemiology Branch, Department of Epidemiology, School of Public Health, Seoul National University, Seoul, Korea.
Joohon
J
Sung
Department of Biomedical Sciences, Seoul National University Graduate School, Seoul, Korea.|Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea.|Medical Research Center, Genomic Medicine Institute (GMI), Seoul National University, Seoul, Korea.
Dong-Sung
DS
Lee
Department of Biochemistry and Molecular Biology, Seoul National University College of Medicine, Seoul, Korea.
Mingon
M
Kang
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Hee Jung
HJ
Son
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
Young-Ho
YH
Kim
D000368:Aged; D044466:Asian People / Q000235:genetics*; D015992:Body Mass Index; D015179:Colorectal Neoplasms / Q000235:genetics* / Q000401:mortality; D055028:Comparative Genomic Hybridization / Q000379:methods*; D056915:DNA Copy Number Variations; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D056910:Republic of Korea; D012307:Risk Factors; D017384:Sequence Deletion; D016019:Survival Analysis
C496405:PKD1L2 protein, human; D043562:Receptors, G-Protein-Coupled
colorectal cancer; copy number; genome study