Association of mitotic regulation pathway polymorphisms with pancreatic cancer risk and outcome.
BACKGROUND
Mitosis is a highly regulated process that serves to ensure the fidelity of cell division. The disruption of mitotic regulators leading to aneuploidy and polyploidy is commonly observed in cancer cells. Single nucleotide polymorphisms (SNP) in regulators of mitosis may promote chromosome missegregation and influence pancreatic cancer and/or survival.


METHODS
Thirty-four SNPs, previously associated with breast cancer risk, from 33 genes involved in the regulation of mitosis, were investigated for associations with pancreatic cancer risk in 1,143 Caucasian patients with pancreatic adenocarcinoma and 1,097 unaffected controls from the Mayo Clinic. Associations with survival from pancreatic cancer were also assessed using 1,030 pancreatic cancer cases with known outcome.


RESULTS
Two SNPs in the APC (rs2431238) and NIN (rs10145182) loci, of 34 examined, were significantly associated with pancreatic cancer risk (P = 0.035 and P = 0.038, respectively). Further analyses of individuals categorized by smoking and body mass index identified several SNPs displaying significant associations (P < 0.05) with pancreatic cancer risk, including APC rs2431238 in individuals with high body mass index (>/=30; P = 0.031) and NIN rs10145182 in ever smokers (P = 0.01). In addition, survival analyses detected significant associations between SNPs in EIF3S10 and overall survival (P = 0.009), SNPs from five genes and survival in resected cancer cases (P < 0.05), and SNPs from two other genes (P < 0.05) and survival of locally advanced cancer cases.


CONCLUSIONS
Common variation in genes encoding regulators of mitosis may independently influence pancreatic cancer susceptibility and survival.
Couch
Fergus J
FJ
Department of Laboratory Medicine and Pathology, Stabile 2-42, Mayo Clinic, 200 First Street Southwest, Rochester, MN 55905, USA. couch.fergus@mayo.edu
Wang
Xianshu
X
Bamlet
William R
WR
de Andrade
Mariza
M
Petersen
Gloria M
GM
McWilliams
Robert R
RR
D000230:Adenocarcinoma / Q000235:genetics*; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics; D015992:Body Mass Index; D003598:Cytoskeletal Proteins / Q000235:genetics; D017491:Genes, APC; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008875:Middle Aged; D008938:Mitosis / Q000235:genetics*; D009687:Nuclear Proteins / Q000235:genetics; D010190:Pancreatic Neoplasms / Q000235:genetics* / Q000401:mortality; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
D014408:Biomarkers, Tumor; D003598:Cytoskeletal Proteins; C512806:NIN protein, human; D009687:Nuclear Proteins