PMID- 25203737
OWN - NLM
STAT- MEDLINE
DCOM- 20150611
LR  - 20211021
IS  - 1744-6880 (Electronic)
IS  - 1744-6872 (Print)
IS  - 1744-6872 (Linking)
VI  - 24
IP  - 11
DP  - 2014 Nov
TI  - Single nucleotide polymorphisms in AREG and EREG are prognostic biomarkers in 
      locally advanced gastric cancer patients after surgery with curative intent.
PG  - 539-47
LID - 10.1097/FPC.0000000000000087 [doi]
AB  - OBJECTIVE: Amphiregulin (AREG) and epiregulin (EREG) are important ligands to the 
      epithelial growth factor receptor, which is involved in the regulation of 
      progression and stemness in gastric cancer (GC). This study investigated whether 
      frequent single nucleotide polymorphisms (SNPs) in genes of AREG and EREG are 
      associated with recurrence-free survival and overall survival in patients with 
      locally advanced GC. METHODS: SNPs with a minor allele frequency of at least 10% 
      were analyzed using direct DNA sequencing in two independent study populations. 
      RESULTS: The minor allele of AREG rs1615111 was associated with a significantly 
      higher 3-year recurrence rate and lower 3-year survival rate [hazard ratio 
      (HR)=2.21 and 2.35, respectively] compared with patients homozygous for the 
      dominant allele G. The value for overall survival could be validated with a HR of 
      2.54 (P=0.018) in an independent cohort. Patients homozygous for the minor allele 
      A of EREG rs12641042 had a significantly higher 3-year survival rate than 
      patients with allele C (HR 0.48; P=0.034), but significance was lost in 
      multivariable analysis (P=0.066). The value of rs12641042 could not be validated 
      (P=0.98). Exploratory multivariable subgroup analysis showed the strongest 
      prognostic value for rs1615111 in tumors with a diffuse histology (Pfor 
      interaction=0.004). CONCLUSION: AREG rs1615111, located in the AREG genomic 
      region, can significantly define different prognostic cohorts in locally advanced 
      GC. This value is most evident in GC patients with diffuse histology, which might 
      be relevant as none of the trials testing epithelial growth factor receptor 
      inhibitors has been enriched for diffuse histology or a molecularly defined 
      population.
FAU - Wakatsuki, Takeru
AU  - Wakatsuki T
AD  - aSharon Carpenter Laboratory, USC/Norris Comprehensive Cancer Center, Keck School 
      of Medicine, Los Angeles, California bMemorial Sloan Kettering Cancer Center, New 
      York, New York, USA cDepartment of Gastroenterology Center, Cancer Institute 
      Hospital, Tokyo Departments of dGastroenterology eSurgery, School of Medicine, 
      Kitasato University, Sagamihara, Japan fDepartment of Hematology and Oncology, 
      University Hospital Grosshadern, University of Munich, Munich, Germany.
FAU - Stintzing, Sebastian
AU  - Stintzing S
FAU - Zhang, Wu
AU  - Zhang W
FAU - Yang, Dongyun
AU  - Yang D
FAU - Azuma, Mizutomo
AU  - Azuma M
FAU - Ning, Yan
AU  - Ning Y
FAU - Yamauchi, Shinichi
AU  - Yamauchi S
FAU - Matsusaka, Satoshi
AU  - Matsusaka S
FAU - Volz, Nico B
AU  - Volz NB
FAU - Sunakawa, Yu
AU  - Sunakawa Y
FAU - Koizumi, Wasaburo
AU  - Koizumi W
FAU - Watanabe, Masahiko
AU  - Watanabe M
FAU - Barzi, Afsaneh
AU  - Barzi A
FAU - El Khoueiry, Anthony B
AU  - El Khoueiry AB
FAU - Shah, Manish A
AU  - Shah MA
FAU - Lenz, Heinz-Josef
AU  - Lenz HJ
LA  - eng
GR  - P30 CA014089/CA/NCI NIH HHS/United States
GR  - 5P30CA014089-27S1/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Pharmacogenet Genomics
JT  - Pharmacogenetics and genomics
JID - 101231005
RN  - 0 (AREG protein, human)
RN  - 0 (Amphiregulin)
RN  - 0 (Biomarkers, Tumor)
RN  - 0 (EGF Family of Proteins)
RN  - 0 (EREG protein, human)
RN  - 0 (Epiregulin)
SB  - IM
MH  - Aged
MH  - Amphiregulin
MH  - Biomarkers, Tumor/*metabolism
MH  - Cohort Studies
MH  - EGF Family of Proteins/*genetics
MH  - Epiregulin/*genetics
MH  - Female
MH  - Humans
MH  - Male
MH  - *Polymorphism, Single Nucleotide
MH  - Prognosis
MH  - Stomach Neoplasms/metabolism/*surgery
PMC - PMC4190127
MID - NIHMS617440
COIS- Conflict of interest: The authors declare to have no conflict of interest.
EDAT- 2014/09/10 06:00
MHDA- 2015/06/13 06:00
PMCR- 2015/11/01
CRDT- 2014/09/10 06:00
PHST- 2014/09/10 06:00 [entrez]
PHST- 2014/09/10 06:00 [pubmed]
PHST- 2015/06/13 06:00 [medline]
PHST- 2015/11/01 00:00 [pmc-release]
AID - 10.1097/FPC.0000000000000087 [doi]
PST - ppublish
SO  - Pharmacogenet Genomics. 2014 Nov;24(11):539-47. doi: 
      10.1097/FPC.0000000000000087.