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No association of risk variants for diabetes and obesity with breast cancer: the Multiethnic Cohort and PAGE studies.

ABSTRACT: Body mass index is an established risk factor for postmenopausal breast cancer. Epidemiologic studies have also reported a positive association between type 2 diabetes (T2D) and breast cancer risk.To investigate a genetic basis linking these common phenotypes with breast cancer, we tested 31 common variants for T2D and obesity in a case-control study of 1,915 breast cancer cases and 2,884 controls nested within the Multiethnic Cohort (MEC) study.Following adjustment for multiple tests, we found no significant association between any variant and breast cancer risk. Summary scores comprising the numbers of risk alleles for T2D and/or obesity were also not found to be significantly associated with breast cancer risk.Our findings provide no evidence for association between established T2D and/or obesity risk variants and breast cancer risk among women of various ethnicities.These results suggest that the potential for a shared biology between T2D/obesity and breast cancer is not due to pleiotropic effects of these risk variants.

SUBMITTER: Chen F

PROVIDER: S-EPMC4201112 | biostudies-literature | 2011 May

REPOSITORIES: biostudies-literature

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No association of risk variants for diabetes and obesity with breast cancer: the Multiethnic Cohort and PAGE studies.

Chen Fang F 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 20110225 5

<h4>Background</h4>Body mass index is an established risk factor for postmenopausal breast cancer. Epidemiologic studies have also reported a positive association between type 2 diabetes (T2D) and breast cancer risk.<h4>Methods</h4>To investigate a genetic basis linking these common phenotypes with breast cancer, we tested 31 common variants for T2D and obesity in a case-control study of 1,915 breast cancer cases and 2,884 controls nested within the Multiethnic Cohort (MEC) study.<h4>Results</h4 ...[more]

PMID: 21357383

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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.

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No association of risk variants for diabetes and obesity with breast cancer: the Multiethnic Cohort and PAGE studies.

Publications

No association of risk variants for diabetes and obesity with breast cancer: the Multiethnic Cohort and PAGE studies.

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