Dataset Information

No association of type 2 diabetes risk variants and prostate cancer risk: the multiethnic cohort and PAGE.

ABSTRACT: BACKGROUND:Epidemiologic studies have found evidence of an inverse association between diabetes status and prostate cancer risk. We explored the hypothesis that common genetic variation may explain, in part, the inverse association between diabetes and prostate cancer. METHODS:We tested 17 diabetes risk variants for association with prostate cancer risk in a prostate cancer case-control study of 2,746 cases and 3,317 controls from five racial/ethnic groups in the Multiethnic Cohort (MEC) study. RESULTS:After adjustment for multiple testing, none of the alleles were statistically significantly associated with prostate cancer risk. Aggregate scores that sum the risk alleles were also not significantly associated with risk. CONCLUSIONS:We did not find evidence of association of this set of diabetes risk alleles with prostate cancer. IMPACT:Resequencing and fine-mapping of the loci for diabetes and prostate cancer that were identified by genome-wide association studies are necessary to understand any genetic contribution for the inverse association between these common diseases.

SUBMITTER: Waters KM

PROVIDER: S-EPMC3175821 | biostudies-literature | 2011 Sep

REPOSITORIES: biostudies-literature

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No association of type 2 diabetes risk variants and prostate cancer risk: the multiethnic cohort and PAGE.

Waters Kevin M KM Wilkens Lynne R LR Monroe Kristine R KR Stram Daniel O DO Kolonel Laurence N LN Henderson Brian E BE Le Marchand Loïc L Haiman Christopher A CA

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20110712 9

<h4>Background</h4>Epidemiologic studies have found evidence of an inverse association between diabetes status and prostate cancer risk. We explored the hypothesis that common genetic variation may explain, in part, the inverse association between diabetes and prostate cancer.<h4>Methods</h4>We tested 17 diabetes risk variants for association with prostate cancer risk in a prostate cancer case-control study of 2,746 cases and 3,317 controls from five racial/ethnic groups in the Multiethnic Cohor ...[more]

PMID: 21750171

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Project description:BACKGROUND:The mitochondrial genome encodes for thirty-seven proteins, among them thirteen are essential for the oxidative phosphorylation (OXPHOS) system. Inherited variation in mitochondrial genes may influence cancer development through changes in mitochondrial proteins, altering the OXPHOS process and promoting the production of reactive oxidative species. METHODS:To investigate the association between mitochondrial genetic variation and breast cancer risk, we tested 314 mitochondrial SNPs (mtSNPs), capturing four complexes of the mitochondrial OXPHOS pathway and mtSNP groupings for rRNA and tRNA, in 2,723 breast cancer cases and 3,260 controls from the Multiethnic Cohort Study. RESULTS:We examined the collective set of 314 mtSNPs as well as subsets of mtSNPs grouped by mitochondrial OXPHOS pathway, complexes, and genes, using the sequence kernel association test and adjusting for age, sex, and principal components of global ancestry. We also tested haplogroup associations using unconditional logistic regression and adjusting for the same covariates. Stratified analyses were conducted by self-reported maternal race/ethnicity. No significant mitochondrial OXPHOS pathway, gene, and haplogroup associations were observed in African Americans, Asian Americans, Latinos, and Native Hawaiians. In European Americans, a global test of all genetic variants of the mitochondrial genome identified an association with breast cancer risk (P = 0.017, q = 0.102). In mtSNP-subset analysis, the gene MT-CO2 (P = 0.001, q = 0.09) in Complex IV (cytochrome c oxidase) and MT-ND2 (P = 0.004, q = 0.19) in Complex I (NADH dehydrogenase (ubiquinone)) were significantly associated with breast cancer risk. CONCLUSIONS:In summary, our findings suggest that collective mitochondrial genetic variation and particularly in the MT-CO2 and MT-ND2 may play a role in breast cancer risk among European Americans. Further replication is warranted in larger populations and future studies should evaluate the contribution of mitochondrial proteins encoded by both the nuclear and mitochondrial genomes to breast cancer risk.

Dataset Information

No association of type 2 diabetes risk variants and prostate cancer risk: the multiethnic cohort and PAGE.

Publications

No association of type 2 diabetes risk variants and prostate cancer risk: the multiethnic cohort and PAGE.

Similar Datasets

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