文摘
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 m>PKD1L2m> deletion region. High frequency of m>PKD1L2m> CNV was observed in CRC cases. We validated the association between m>PKD1L2m> variation and CRC risk in 1,874 cases and 2,088 controls (OR = 1.44, 95% CI = 1.04–1.98, m>pm> = 0.028). Additionally, m>PKD1L2m> CNV is associated with increased CRC risk in patients younger than 50 years (OR = 2.14, 95% CI 1.39–3.30, m>pm> = 5.8 × 10−4). In subgroup analysis according to body mass index (BMI), we found that the CN loss of m>PKD1L2m> with BMI above or equal to 25 exhibited a significant increase in CRC risk (OR = 2.29, 95% CI 1.29–4.05, m>pm> = 0.005). m>PKD1L2m> 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, m>pm>= 4.8 × 10−5). Moreover, we found that m>PKD1L2m> variation in obese patients (BMI ≥ 25) was associated with poor survival rate (m>pm> = 0.026). Our results suggest that the common m>PKD1L2m> CNV is associated with CRC, and m>PKD1L2m> CNV with high BMI and/or age below 50 exhibited a significant increased risk of CRC. In obese patients, m>PKD1L2m> variation was associated with poor survival.