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Pancreas. 2011 Jul;40(5):657-63. doi: 10.1097/MPA.0b013e31821268d1.

Genetic effects and modifiers of radiotherapy and chemotherapy on survival in pancreatic cancer.

Author information

1
Department of Epidemiology and Public Health, School of Public Health and School of Medicine, Yale University, New Haven, CT 06520-8034, USA.

Abstract

OBJECTIVES:

Germ-line genetic variation may affect clinical outcomes of cancer patients. We applied a candidate-gene approach to evaluate the effect of putative markers on survival of patients with pancreatic cancer. We also examined gene-radiotherapy and gene-chemotherapy interactions, aiming to explain interindividual differences in treatment outcomes.

METHODS:

In total, 211 patients with pancreatic cancer were recruited in a population-based study. Sixty-four candidate genes associated with cancer survival or treatment response were selected from existing publications. Genotype information was obtained from a previous genome-wide association study data set. The main effects of genetic variation and gene-specific treatment interactions on overall survival were examined by proportional hazards regression models.

RESULTS:

Fourteen genes showed evidence of association with pancreatic cancer survival. Among these, rs1760217, located at the DPYD gene; rs17091162 at SERPINA3; and rs2231164 at ABCG2 had the lowest P of 10(-4.60), 0.0013, and 0.0023, respectively. We also observed that 2 genes, RRM1 and IQGAP2, had significant interactions with radiotherapy in association with survival, and 2 others, TYMS and MET, showed evidence of interaction with 5-fluorouracil and erlotinib, respectively.

CONCLUSIONS:

Our study suggested significant associations between germ-line genetic polymorphisms and overall survival in pancreatic cancer, as well as survival interactions between various genes and radiotherapy and chemotherapy.

PMID:
21487324
PMCID:
PMC3116071
DOI:
10.1097/MPA.0b013e31821268d1
[Indexed for MEDLINE]
Free PMC Article

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