PMID- 15217929
OWN - NLM
STAT- MEDLINE
DCOM- 20050103
LR  - 20230202
IS  - 1078-0432 (Print)
IS  - 1078-0432 (Linking)
VI  - 10
IP  - 12 Pt 1
DP  - 2004 Jun 15
TI  - Serum levels of insulin growth factor (IGF-I) and IGF-binding protein predict 
      risk of second primary tumors in patients with head and neck cancer.
PG  - 3988-95
AB  - PURPOSE: Second primary tumors (SPTs) are a hallmark of head and neck squamous 
      cell carcinomas (HNSCCs). Serum levels of insulin growth factors (IGFs) and their 
      binding proteins (IGFBPs) have been associated with subsequent development of 
      several epithelial cancers in prospective studies. EXPERIMENTAL DESIGN: To 
      examine the role of IGFs in SPT development, we conducted a nested case-control 
      study within a randomized, placebo-controlled chemoprevention trial in patients 
      with early-stage HNSCC. We compared prediagnostic serum IGF-I and IGFBP-3 levels 
      in 80 patients who subsequently developed SPTs and 173 controls (patients without 
      SPTs) matched to the cases on age (+/-5 years), sex, ethnicity, year of 
      randomization, and length of follow-up. RESULTS: The cases exhibited 
      significantly higher levels of IGF-I and IGFBP-3 than did the controls (P = 0.001 
      and 0.019, respectively). Elevated IGF-I levels were associated with a 3.66-fold 
      significantly increased risk of SPT. Lower and higher IGFBP-3 levels were 
      associated with a 2.22- and 7.12-fold significant increased risk, respectively. 
      The median SPT-free time was significantly shorter in patients with higher IGF-I 
      levels than in patients with lower IGF-I levels (P < 0.0001). A similar trend was 
      observed for IGFBP-3 (P = 0.002). Moreover, in the Cox proportional hazards 
      model, higher IGF-I levels were significantly associated with increased risk of 
      SPT with a hazard ratio of 2.78. Patients with the lower and higher IGFBP-3 
      levels also exhibited significantly increased risks with hazard ratios of 1.65 
      and 2.17, respectively. CONCLUSIONS: This is the first study demonstrating that 
      higher IGF-I levels, and lower and higher IGFBP-3 levels are risk factors for SPT 
      development. Thus, measuring serum IGF-I and IGFBP-3 levels may be useful markers 
      in assessing the risk of second tumors in patients successfully treated for their 
      index cancer.
FAU - Wu, Xifeng
AU  - Wu X
AD  - Department of Epidemiology, The University of Texas M. D. Anderson Cancer Center, 
      Houston, Texas, USA. xwu@mdanderson.org
FAU - Zhao, Hua
AU  - Zhao H
FAU - Do, Kim-Anh
AU  - Do KA
FAU - Johnson, Marcella M
AU  - Johnson MM
FAU - Dong, Qiong
AU  - Dong Q
FAU - Hong, Waun Ki
AU  - Hong WK
FAU - Spitz, Margaret R
AU  - Spitz MR
LA  - eng
GR  - CA 52051/CA/NCI NIH HHS/United States
GR  - CA74880/CA/NCI NIH HHS/United States
GR  - CA86390/CA/NCI NIH HHS/United States
PT  - Clinical Trial
PT  - Journal Article
PT  - Randomized Controlled Trial
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Clin Cancer Res
JT  - Clinical cancer research : an official journal of the American Association for 
      Cancer Research
JID - 9502500
RN  - 0 (Insulin-Like Growth Factor Binding Proteins)
RN  - 0 (Placebos)
RN  - 67763-96-6 (Insulin-Like Growth Factor I)
SB  - IM
MH  - Adult
MH  - Aged
MH  - Aged, 80 and over
MH  - Carcinoma, Squamous Cell/blood/*pathology
MH  - Case-Control Studies
MH  - Enzyme-Linked Immunosorbent Assay
MH  - Female
MH  - Head and Neck Neoplasms/blood/*pathology
MH  - Humans
MH  - Insulin-Like Growth Factor Binding Proteins/*blood
MH  - Insulin-Like Growth Factor I/*biosynthesis
MH  - Logistic Models
MH  - Male
MH  - Middle Aged
MH  - Multivariate Analysis
MH  - Neoplasms, Second Primary/blood/*diagnosis
MH  - Odds Ratio
MH  - Placebos
MH  - Proportional Hazards Models
MH  - Random Allocation
MH  - Risk
MH  - Risk Factors
MH  - Smoking
MH  - Time Factors
EDAT- 2004/06/26 05:00
MHDA- 2005/01/04 09:00
CRDT- 2004/06/26 05:00
PHST- 2004/06/26 05:00 [pubmed]
PHST- 2005/01/04 09:00 [medline]
PHST- 2004/06/26 05:00 [entrez]
AID - 10/12/3988 [pii]
AID - 10.1158/1078-0432.CCR-03-0762 [doi]
PST - ppublish
SO  - Clin Cancer Res. 2004 Jun 15;10(12 Pt 1):3988-95. doi: 
      10.1158/1078-0432.CCR-03-0762.