Association of breast cancer susceptibility variants with risk of pancreatic cancer.
BACKGROUND
A number of susceptibility genes are common to breast and pancreatic cancer. Recently, several breast cancer susceptibility loci have been identified through genome-wide association studies. Here we evaluated possible associations between these single nucleotide polymorphisms (SNP) and pancreatic cancer risk.


METHODS
Ten SNPs from FGFR2, TOX3, MAP3K1, H19, LSP1, chromosome 8q24, CASP8, and LUM were investigated for associations with pancreatic cancer risk following genotyping in 1,143 Caucasian individuals with pancreatic adenocarcinoma and 1,097 unaffected controls from a clinic-based pancreatic cancer case-control study.


RESULTS
CASP8 rs1045485 [odds ratio (OR), 0.78; 95% confidence interval (95% CI), 0.65-0.9; P = 0.005] and MAP3K1 rs889312 (OR, 0.85; 95% CI, 0.74-0.97; P = 0.017) showed evidence of association with risk of pancreatic cancer. The CASP8 rs1045485 association was evident in ever smokers (P = 0.002), but not in nonsmokers (P = 0.55), and the effect was strongest in heavy smokers (OR, 0.52; 95% CI, 0.29-0.93; P = 0.03). In contrast the MAP3K1 rs889312 association was only evident in nonsmokers (OR, 0.78; 95% CI, 0.64-0.95; P = 0.01). In addition, evaluation of the influence of the 10 SNPs on survival detected significant associations between outcome for locally advanced pancreatic cancer cases and both 8q rs6983561 (P = 0.045) and LUM rs2268578 (P = 0.02).


CONCLUSIONS
Association studies in a large pancreatic case-control study indicate that SNPs associated with breast cancer may also be associated with pancreatic cancer susceptibility and survival.
Department of Laboratory Medicine and Pathology, Mayo Clinic, Rochester, Minnesota 55905, USA. couch.fergus@mayo.edu
Fergus J
FJ
Couch
Xianshu
X
Wang
Robert R
RR
McWilliams
William R
WR
Bamlet
Mariza
M
de Andrade
Gloria M
GM
Petersen
D000230:Adenocarcinoma / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D000368:Aged; D014408:Biomarkers, Tumor / Q000235:genetics*; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology; D016022:Case-Control Studies; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D004273:DNA, Neoplasm / Q000032:analysis / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009367:Neoplasm Staging; D010190:Pancreatic Neoplasms / Q000453:epidemiology / Q000235:genetics* / Q000473:pathology; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D011379:Prognosis; D012307:Risk Factors; D015996:Survival Rate
D014408:Biomarkers, Tumor; D004273:DNA, Neoplasm