Five common variants were associated with pancreatic cancer at nominal statistical significance (P < 0.05) with the strongest finding for mt5460g in the ND2 gene [OR = 3.9; 95% confidence interval (CI), 1.5-10; P = 0.004] which encodes an A331T substitution.
Haplogroup K was nominally associated with reduced pancreatic cancer risk (OR = 0.32; 95% CI, 0.13-0.76; P = 0.01) when compared with the most common haplogroup, H. A total of 19 haplogroup-specific rare variants yielded nominal statistically significant associations (P < 0.05) with pancreatic cancer risk, with the majority observed in genes involved in oxidative phosphorylation. Weighted-sum statistics were used to identify an aggregate effect of variants in the 22 mitochondrial tRNAs on pancreatic cancer risk (P = 0.02). While the burden of singleton variants in the HV2 and 12S RNA regions was three times higher among European haplogroup N cases than controls, the prevalence of singleton variants in ND4 and ND5 was two to three times higher among African haplogroup L cases than in controls. Together, the results of this study provide evidence that aggregated common and rare variants and the accumulation of singleton variants are important contributors to pancreatic cancer risk.
Cancer Res (1538-7445)
Institute for Human Genetics, University of California, San Francisco, California, USA.
Cancer Res. 2012 Feb;72(3):686-95
Español | English
© Galenicom 1999-2013