Seizure 6-like (SEZ6L) gene and risk for lung cancer.

Seizure 6-like (SEZ6L) gene and risk for lung cancer. Research Abstract Details 

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Seizure 6-like (SEZ6L) gene and risk for lung cancer. Abstract Text:

Ivan P Gorlov,Peter Meyer,Triantafillos Liloglou,Jonathan Myles,Melanie Barbara Boettger,Adrian Cassidy,Luc Girard,John D Minna,Reiner Fischer,Stephen Duffy,Margaret R Spitz,Karl Haeussinger,Stefan Kammerer,Charles Cantor,Rainer Dierkesmann,John K Field,Christopher I Amos,

DNA pooling in combination with high-throughput sequencing was done as a part of the Sequenom-Genefinder project. In the pilot study, we tested 83,715 single nucleotide polymorphisms (SNP), located primarily in gene-based regions, to identify polymorphic susceptibility variants for lung cancer. For this pilot study, 369 male cases and 287 controls of both sexes (white Europeans of Southern German origin) were analyzed. The study identified a candidate region in 22q12.2 that contained numerous SNPs showing significant case-control differences and that coincides with a region that was shown previously to be frequently deleted in lung cancer cell lines. The candidate region overlies the seizure 6-like (SEZ6L) gene. The pilot study identified a polymorphic Met430Ile substitution in the SEZ6L gene (SNP rs663048) as the top candidate for a variant modulating risk of lung cancer. Two replication studies were conducted to assess the association of SNP rs663048 with lung cancer risk. The M. D. Anderson Cancer Center study included 289 cases and 291 controls matched for gender, age, and smoking status. The Liverpool Lung Project (a United Kingdom study) included 248 cases and 233 controls. Both replication studies showed an association of the rs663048 with lung cancer risk. The homozygotes for the variant allele had more than a 3-fold risk compared with the wild-type homozygotes [combined odds ratio (OR), 3.32; 95% confidence interval (95% CI), 1.81-7.21]. Heterozygotes also had a significantly elevated risk of lung cancer from the combined replication studies with an OR of 1.15 (95% CI, 1.04-1.59). The effect remained significant after adjusting for age, gender, and pack-years of tobacco smoke. We also compared expression of SEZ6L in normal human bronchial epithelial cells (n = 7), non-small cell lung cancer (NSCLC; n = 52), and small cell lung cancer (SCLC; n = 22) cell lines by using Affymetrix HG-U133A and HG-U133B GeneChips. We found that the average expression level of SEZ6L in NSCLC cell lines was almost two times higher and in SCLC cell lines more than six times higher when compared with normal lung epithelial cell lines. Using the National Center for Biotechnology Information Gene Expression Omnibus database, we found a approximately 2-fold elevated and statistically significant (P = 0.004) level of SEZ6L expression in tumor samples compared with normal lung tissues. In conclusion, the results of these studies representing 906 cases compared with 811 controls indicate a role of the SEZ6L Met430Ile polymorphic variant in increasing lung cancer risk.

Seizure 6-like (SEZ6L) gene and risk for lung cancer. Publishing Authors By Initials

IP Gorlov,P Meyer,T Liloglou,J Myles,MB Boettger,A Cassidy,L Girard,JD Minna,R Fischer,S Duffy,MR Spitz,K Haeussinger,S Kammerer,C Cantor,R Dierkesmann,JK Field,CI Amos,

For similar investigative techniques: epidemiologic methods: statistics as topic: probability: risk: risk factors research abstracts see: investigative techniques: epidemiologic methods: statistics as topic: probability: risk: risk factors research

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Seizure 6-like (SEZ6L) gene and risk for lung cancer. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Cancer research

VOLUME: 67

Page Numbers: 8406-11

Journal Abbreviation: Cancer Res.

ISSN: 0008-5472

DAY: 1

MONTH: Sep

YEAR: 2007

Seizure 6-like (SEZ6L) gene and risk for lung cancer. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 2984705

Seizure 6-like (SEZ6L) gene and risk for lung cancer. Keywords Mesh Terms:

KEYWORDS: Risk Factors

MESH TERMS: genetics

Chemical & Substance for Abstract: Seizure 6-like (SEZ6L) gene and risk for lung cancer. Information

Substance Name: SEZ6L protein, human

Registry Number: 0

Grant and Affiliation Information for Seizure 6-like (SEZ6L) gene and risk for lung cancer.

AFFILIATION: Department of Epidemiology, The University of Texas M D Anderson Cancer Center, Houston, TX 77030, USA.

Country: United States

AGENCY: United States NCI

GRANT: R01 CA55769

ACRONYM: CA

MEDLINETA: Cancer Res

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