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Leukocyte telomere length‐related genetic variants in 1p34.2 and 14q21 loci contribute to the risk of esophageal squamous cell carcinoma
Author(s) -
Shi Juan,
Sun Fang,
Peng Li,
Li Bo,
Liu Li,
Zhou Changchun,
Han Jianjun,
Zhang Li,
Zhou Liqing,
Zhang Xiaojiao,
Pu Honglei,
Tong Lei,
Yuan Qipeng,
Song Xianrang,
Yang Ming
Publication year - 2012
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.27959
Subject(s) - telomere , single nucleotide polymorphism , genotype , biology , allele , carcinogenesis , esophageal squamous cell carcinoma , esophageal cancer , genetics , genome wide association study , carcinoma , medicine , cancer , gene
Short leukocyte telomere length has been associated with significantly increased risk of esophageal cancer. A previous genome‐wide association study demonstrated that four SNPs (rs398652 on 14q21, rs621559 on 1p34.2, rs6028466 on 20q11.22 and rs654128 on 6q22.1) were associated with leukocyte telomere length in Caucasians. However, the role of these genetic variants on esophageal squamous cell carcinoma (ESCC) susceptibility is still unknown. Therefore, we investigated whether these polymorphisms have impact on leukocyte telomere length and the risk of ESCC in Chinese. After measuring leukocyte telomere length of 550 healthy individuals, we observed that both rs621559 and rs398652 genetic variants are significantly associated with leukocyte telomere length. On the basis of analyzing 1550 ESCC patients and frequency‐matched 1620 controls from 4 medical centers in China, we found that 0.71‐fold decreased risk of ESCC is associated with the rs621559 AA genotype compared with the rs621559 GG genotype ( p = 5.9 × 10 −6 ). We also detected a moderately increased OR for ESCC that was associated with the 14q21 rs398652 G allele ( p = 6.5 × 10 −4 ). It has been shown that both rs621559 and rs398652 polymorphisms were significantly associated with ESCC risk in additive, recessive or dominant genetic models. Stratified analyses demonstrated that these associations were more pronounced in males. Our results highlight the complexity of genetic regulation of telomere length and further support the important role of telomere in carcinogenesis.

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