Background: Genome-wide association studies have demonstrated the association between single-nucleotide polymorphisms (SNPs) in the chromosome 15q25.1 region and an increased lung cancer risk through smoking behavior mediated by nicotine dependence susceptibility. Cigarette smoking is also a major risk factor for development of pancreatic cancer and has been reported to be associated with early onset of this disease. Therefore, we hypothesize that variation in this region may influence the age onset of the pancreatic cancer through smoking behavior.

Methods: In this preliminary study, 3 tagging SNPs in 15q25.1 region were genotyped in 427 newly-diagnosed, non-Hispanic White patients with pancreatic cancer. Two of the SNPs, rs7164594 and rs3841324, are in the CHRNA5 gene and the third SNP rs684513 is in PSMA4 gene, respectively.

Results: Our results showed that the two tagging SNPs rs7164594 and rs3841324 in CHRNA5 were not associated with age-associated risk of pancreatic cancer. However, for the tagging SNP rs684513, the variant homozygotes (CC) had a protective effect on age of onset [adjusted HR=0.69 (0.46-1.03), p=0.070], compared with the wild type and heterozygotes (GG+CG), with a 4-years difference in at age of onset [64.81 ± 2.10 vs. 60.60 ± 0.53; log-rank p= 0.042]. Further stratification analysis showed that a reduced risk associated with the variant homozygous (CC) was more pronounced in the subgroup of non-smokers and former smokers [adjusted HR=0.48 (0.26-0.91), p=0.023].

Conclusion and impact: This observation provided preliminary evidence for the association between genetic variant in the chromosomal region 15q25.1 and the age of onset of pancreatic cancer. However, a comprehensive study of all other tagging SNPs covering 15q25.1 region will be worthwhile to conduct.

Citation Format: Chongjuan Wei, Yu-jing Huang, Jane Chen, Mala Pande, Chris Amos, Marsha Frazier. Genetic variants in 15q25.1 and age onset of pancreatic cancer. [abstract]. In: Proceedings of the Eleventh Annual AACR International Conference on Frontiers in Cancer Prevention Research; 2012 Oct 16-19; Anaheim, CA. Philadelphia (PA): AACR; Cancer Prev Res 2012;5(11 Suppl):Abstract nr A25.

©2012 American Association for Cancer Research.
2012