Open AccessGenetic variants at 9p21.3 are associated with risk of esophageal squamous cell carcinoma in a Chinese population
Author(s) -
Lin Xiaoming,
Yan Caiwang,
Gao Yong,
Du Jiangbo,
Zhu Xun,
Yu Fei,
Huang Tongtong,
Dai Juncheng,
Ma Hongxia,
Jiang Yue,
Yin Rong,
Hu Zhibin,
Jin Guangfu,
Xu Lin,
Shen Hongbing
Publication year - 2017
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13130
Subject(s) - odds ratio , allele , confidence interval , locus (genetics) , biology , genome wide association study , population , esophageal cancer , esophageal squamous cell carcinoma , oncology , genetics , medicine , carcinoma , case control study , cancer research , cancer , genotype , gene , single nucleotide polymorphism , environmental health
Genome‐wide association studies have linked genetic variants at 9p21.3 to the risk of multiple cancers. However, the roles of genetic variants at 9p21.3 in esophageal squamous cell carcinoma ( ESCC ) development are largely unknown. We evaluated the genetic variants at 9p21.3 reported in cancer genome‐wide association studies with a case–control study including 2139 ESCC cases and 2273 controls in a Chinese population, and measured the mRNA expression levels of MTAP , CDKN 2A , CDKN 2B , and CDKN 2B‐ AS 1 in paired ESCC tumor and adjacent normal tissues. We found that the G allele of rs7023329 was significantly associated with a decreased risk of ESCC with a per‐allele odds ratio of 0.84 (95% confidence interval, 0.77–0.91; P = 2.95 × 10 −5 ). The rs7023329‐G allele was related to a high expression of MTAP ( P = 0.020). The rs1679013‐C allele was independently associated with an increased risk of ESCC with a per‐allele odds ratio of 1.12 (95% confidence interval, 1.01–1.24; P = 0.039). We also found that the carriers of the risk allele rs1679013‐C had lower expression of CDKN 2B than non‐carriers ( P = 0.035). CDKN 2B was also significantly downregulated in ESCC tumor tissues compared with adjacent normal tissues ( P = 3.50×10 −5 ). Therefore, our findings indicate that genetic variants at 9p21.3 may modulate the expression of MTAP and CDKN 2B and contribute to ESCC susceptibility. This may further advance our understanding of the 9p21.3 locus in cancer development.