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The polymorphism and haplotypes of PIN1 gene are associated with the risk of lung cancer in southern and eastern chinese populations
Author(s) -
Lu Jiachun,
Yang Lei,
Zhao Hongjun,
Liu Bin,
Li Yinyan,
Wu Hongxia,
Li Qingchu,
Zeng Bohang,
Wang Yunnan,
Ji Weidong,
Zhou Yifeng
Publication year - 2011
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.21574
Subject(s) - biology , haplotype , genetics , lung cancer , pin1 , polymorphism (computer science) , gene , genotype , oncology , medicine , isomerase
Abstract Peptidyl‐prolyl cis/trans isomerase (PPIase), PIN1, has been found to be a critical catalyst that involves in multiple oncogenic signaling pathways. Recently, several putative functional polymorphisms of the PIN1 gene have been identified to be associated with cancer risk. In this study, we tested the hypothesis that two common polymorphisms, c.‐842G>C (rs2233678) and c.‐667C>T (rs2233679), in the PIN1 promoter are associated with risk of lung cancer. In two independent case‐control studies of 1,559 lung cancer cases and 1,679 controls conducted in Southern and Eastern Chinese population, we found that compared with the most common c.‐842GG genotype, the carriers of c.‐842C variant genotypes (GC + CC) had a decreased risk of lung cancer (odds ratio [OR] = 0.63, 95% confidence interval [CI] = 0.51–0.78, p = 1.13 × 10 −5 ). Although no association was observed between the c.‐667C>T polymorphism and cancer risk, we found that the haplotype “C‐C” had a greater protective effect (OR = 0.39, 95% CI = 0.23–0.67, p = 5.03 × 10 −4 ). The stratification analysis showed that the protective role of c.‐842C variants was more pronounced in current smokers ( p = 4.45 × 10 −5 ), especially in male smokers ( p = 6.71 × 10 −6 ) and in those who smoked more than 20 pack‐years ( p = 2.30 × 10 −5 ) and the c.‐842C variant genotypes interacted with smoking status ( P interaction = 0.019) or pack‐years smoked ( P interaction = 0.008) on reducing cancer risk. Further functional assay revealed that the c.‐842C variant allele had a lower transcription activity in luciferase assay and a lower DNA‐binding ability with nuclear proteins, and low transcription activity in western blot assay. In conclusions, our data suggest that functional c.‐842C variants and haplotype “C‐C” in the PIN1 promoter contribute to decreased risk of lung cancer by diminishing the promoter activity, which may be susceptibility biomarkers for lung cancer. Hum Mutat 32:1299–1308, 2011. ©2011 Wiley Periodicals, Inc.