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Single Nucleotide Polymorphisms and Survival After Pancreatic Cancer Resection

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Key Points

  • Patients with T/T genotype at rs353630 (CHI3L2) had a greater risk of tumor-associated mortality.
  • Patients with A/A genotype at rs684559 (CD44) also had a greater risk of tumor-related mortality.

In a study reported in JAMA Surgery, Dimitrakopoulos et al found two single nucleotide polymorphisms (SNPs) in noncoding, functional regions of genes that regulate cancer progression. They were associated with survival after resection of pancreatic ductal adenocarcinoma.

The study involved genome-wide screening for identification of functional SNPs that affect pancreatic ductal adenocarcinoma survival in a European cohort of patients who underwent pancreatic resection (n = 195). It also entailed the use of a Cancer Genome Atlas cohort for validation (n = 136).

SNPs Associated With Risk

Two SNPs in noncoding, functional regions of genes active in regulating cancer progression, invasion, and metastasis were identified, consisting of CHI3L2 SNP rs684559 and CD44 SNP rs353630. For the merged cohorts, compared with 26 patients with T/T genotype at rs353630, 302 patients with a C allele had significantly better tumor-associated survival (hazard ratio [HR] = 0.40, P = 1.20 × 10−5). Compared with 48 patients with A/A genotype at rs684559, 281 with a G allele had significantly better tumor-associated survival (HR = 0.44, P = 2.00 × 104). Patients with the risk alleles at 1 of both SNP loci had a 2.63-fold increased risk for tumor-associated death compared with those with protective genotypes (HR = 0.38, P = 1.0 × 108).

The investigators concluded, “The identified polymorphisms may serve as a noninvasive biomarker signature of prospective survival after pancreatic resection that is readily available at the time of pancreatic ductal adenocarcinoma diagnosis. This signature can be used to identify a subset of high-risk patients with pancreatic ductal adenocarcinoma with very low survival probability who might be eligible for inclusion in clinical trials of new therapeutic strategies, including neoadjuvant chemotherapy protocols. In addition, the biological knowledge about these SNPs could help guide the development of individualized genomic strategies for pancreatic ductal adenocarcinoma therapies.”

Lukasz Filip Grochola, MD, PhD, of the Department of Visceral and Thoracic Surgery, Cantonal Hospital of Winterthur, and Niko Beerenwinkel, PhD, of the Department of Biosystems Science and Engineering, ETH Zurich, Basel, Switzerland, are the corresponding authors for the JAMA Surgery article.

Disclosure: The study was supported by grants from the Swiss Cancer Research Foundation, EMDO Foundation, and Science Foundation for Oncology. The study authors’ full disclosures can be found at jamanetwork.com.

The content in this post has not been reviewed by the American Society of Clinical Oncology, Inc. (ASCO®) and does not necessarily reflect the ideas and opinions of ASCO®.


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