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  • 1
    In: Gut, BMJ, Vol. 63, No. 5 ( 2014-05), p. 800-807
    Type of Medium: Online Resource
    ISSN: 0017-5749 , 1468-3288
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    Language: English
    Publisher: BMJ
    Publication Date: 2014
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  • 2
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 71, No. 8_Supplement ( 2011-04-15), p. 2755-2755
    Abstract: Excess body weight is thought to account for 25 to 30% of common cancers. As the prevalence of obesity increases worldwide, the number of obesity-related cancers is expected to rise. Recent genome-wide association studies (GWAS) have identified common genetic variants associated with obesity and related metabolic conditions, such as type-2 diabetes. However, the mechanisms underlying these associations are unclear. Given that diet plays a critical role in energy balance and glucose metabolism, it is possible that some of these variants affect metabolic disease risk through an effect on food choices. As part of the Population Architecture using Genomics and Epidemiology (PAGE) initiative, we investigated the associations of 31 risk variants identified in published GWAS of obesity and type-2 diabetes with 50 dietary phenotypes (dietary patterns, macronutrients, food groups, and candidate foods) as measured by a quantitative food frequency questionnaire in the Multiethnic Cohort Study. Participants of five race/ethnic groups (African Americans, Native Hawaiians, Japanese Americans, Latinos, and Whites) were genotyped for 12 obesity (n=13,181) or 19 type-2 diabetes (n=25,273) risk variants. Linear or logistic regression was employed to test for associations, while adjusting for age, sex and ethnicity. Using an additive risk model for genotypes, we found 37 associations with dietary phenotypes (p-value & lt;0.01) for 17 of the 31 SNPs. Rs8050136, a variant located within the FTO gene which is highly expressed in the hypothalamus and is associated with obesity and type-2 diabetes, had the greatest number of associations (n=9), mostly with macronutrients. Among participants who self-reported as non-diabetic at baseline, for a per-allele change, there was a 0.23±0.076 increase in % calories from fat (p=0.002), mainly from monounsaturated fats, and a 0.29±0.095 decrease in % calories from carbohydrates (p=0.002). These associations remained even after additional adjustments for calories and physical activity. We also found that carriers of the risk allele had an increase in % calories from protein (p=0.013) and were less likely to add salt to foods (p=0.007). The directions of these associations were consistent across sexes and racial/ethnic groups. Consistent with our results, several small studies (4 in children and 3 in adults) reported higher energy intake, increased energy intake from fat, and/or diminished satiety among individuals with the risk allele. Replication studies are ongoing in PAGE. Methods to adjust for multiple comparisons among correlated phenotypes are being applied. In conclusion, these data suggest that the association of rs8050136 with obesity may at least partially be the result of a dietary preference for fat. If reproduced, these data may have relevance to the prevention of obesity and obesity-related cancers in risk allele carriers. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 102nd Annual Meeting of the American Association for Cancer Research; 2011 Apr 2-6; Orlando, FL. Philadelphia (PA): AACR; Cancer Res 2011;71(8 Suppl):Abstract nr 2755. doi:10.1158/1538-7445.AM2011-2755
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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    detail.hit.zdb_id: 410466-3
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  • 3
    In: JNCI: Journal of the National Cancer Institute, Oxford University Press (OUP), Vol. 106, No. 4 ( 2014-4)
    Type of Medium: Online Resource
    ISSN: 1460-2105 , 0027-8874
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    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2014
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    detail.hit.zdb_id: 1465951-7
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  • 4
    In: American Journal of Epidemiology, Oxford University Press (OUP), Vol. 178, No. 5 ( 2013-9-1), p. 780-790
    Type of Medium: Online Resource
    ISSN: 1476-6256 , 0002-9262
    Language: English
    Publisher: Oxford University Press (OUP)
    Publication Date: 2013
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  • 5
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2010
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 19, No. 9 ( 2010-09-01), p. 2351-2356
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 19, No. 9 ( 2010-09-01), p. 2351-2356
    Abstract: Background: Coenzyme Q10 (CoQ10) is a component of the mitochondrial electron transport chain and is considered an important cellular antioxidant. Decreased circulating CoQ10 levels have been reported in women with breast cancer, but evidence is limited. We examined the association of plasma CoQ10 levels with postmenopausal breast cancer risk using prospectively collected blood samples. Methods: Prediagnostic plasma levels of total CoQ10 were measured among 160 incident postmenopausal breast cancer cases and 289 controls in the Multiethnic Cohort Study. Cases and controls were individually matched on age, sex, ethnicity, study location (Hawaii or California), hormone replacement therapy use, date and time of specimen collection, and hours of fasting. Logistic regression was used to compute odds ratios and 95% confidence intervals. Results: Plasma CoQ10 levels were positively associated with breast cancer risk, overall (P = 0.04). The association was stronger after women diagnosed within 1 year of blood draw were excluded to eliminate possible preclinical cases (odds ratio for the highest versus the lowest tertile, 2.26; 95% confidence interval, 1.22-4.19; P for trend = 0.01). Conclusions: Higher CoQ10 levels in postmenopausal women may be associated with increased breast cancer risk. Impact: A potential role for CoQ10 in the development and progression of breast cancer has been postulated, but epidemiologic evidence is lacking. Findings from this prospective cohort study add to the limited literature, indicating the potential positive association of circulating CoQ10 with postmenopausal breast cancer risk. Cancer Epidemiol Biomarkers Prev; 19(9); 2351–6. ©2010 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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  • 6
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2011
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 20, No. 4 ( 2011-04-01), p. 708-710
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 20, No. 4 ( 2011-04-01), p. 708-710
    Abstract: Background: Coenzyme Q10 (CoQ10) is considered to be a potential anticancer agent, but epidemiologic evidence regarding CoQ10 and prostate cancer risk is lacking. We examined the association of circulating CoQ10 levels with prostate cancer risk, using prediagnostic blood samples. Methods: Each of the 307 cases was individually matched to approximately 2 controls, for a total of 596 controls, on age, ethnicity, geographic location, date/time of specimen collection, and hours of fasting. Logistic regression was used to compute ORs and 95% CIs. Results: There was no overall statistically significant association of plasma CoQ10 levels with prostate cancer risk (Ptrend = 0.50). However, after matched sets in which controls who had possible undiagnosed prostate cancer (prostate specific antigen value & gt;4.0) were excluded, the ORs for quintiles 2 to 5 were all less than 1.0. Conclusions: The results suggest the possibility that moderate levels of circulating CoQ10 may be optimal for the reduction of prostate cancer risk; however, the findings were weak and not statistically significant. Because this is the first epidemiologic study of the association between CoQ10 and prostate cancer, further research on this topic is needed. Impact: If a nutritional factor such as CoQ10 were determined to reduce prostate cancer risk, it would have considerable public health significance because of the very high incidence of this cancer. Cancer Epidemiol Biomarkers Prev; 20(4); 708–10. ©2011 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2011
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  • 7
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 72, No. 8_Supplement ( 2012-04-15), p. 1662-1662
    Abstract: Genome-wide association studies of cancer have succeeded in identifying over 100 susceptibility loci, including some, such as those found at chromosome 8q24 and CPTM1L-TERT that influence the risk of several malignancies. As part of the Population Architecture using Genomics and Epidemiology (PAGE) Study, we evaluated whether established risk variants for 18 different cancer sites, excluding the lung, impact the risk of lung cancer. A total of 152 risk variants for these 18 malignancies were selected from genome-wide association studies of cancer published through May, 2009. These SNPs were genotyped in lung cancer case-control studies of the Atherosclerosis Risk in Communities (ARIC; cases/controls=297/3088), Epidemiologic Architecture for Genes Linked to Environment (EAGLE; cases/controls=432/1567), Multiethnic Cohort (MEC; cases/controls=461/9029), and the Women's Health Initiative (WHI; cases/controls=1600/5848). The total study population was comprised of 2,790 lung cancer cases and 19,532 controls of African, American Indian, Asian, European, Latino, and Pacific Islander ancestry. For each study site, unconditional logistic regression was performed to evaluate the association between SNPs and lung cancer risk, adjusting for age, sex, race/ethnicity, and smoking status. A fixed-effect meta-analysis was performed and heterogeneity across study sites was tested. Seventeen of the 152 SNPs were associated with lung cancer risk (nominal P & lt;0.05): five breast cancer SNPs, one glioma SNP, three acute lymphocytic leukemia SNPs, one melanoma SNP, one non-Hodgkin lymphoma SNP, and six prostate cancer SNPs. By chance, only eight associations would be expected for the 152 tests (152 x 0.05=8) performed, suggesting robust significant associations among the 17 associated SNPs. The top associations (P & lt;0.01) were observed for: breast cancer SNP (rs3803662 at TOX3: OR=1.13; P=1.1x10−3), prostate cancer SNP (rs7837688 at 8q24: OR=1.19; P=5.2x10−3), and melanoma SNP (rs910873 at PIGU: OR=0.79; P=5.9x10−3). No evidence of heterogeneous effects across study sites was observed. Other analyses will test for independent genetic effects among the associated loci and examine stratified effects by sex, cell-type, and smoking status. In conclusion, findings from our meta-analysis suggest that lung cancer may share genetic risk factors and common etiologic pathways with several cancer sites. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 1662. doi:1538-7445.AM2012-1662
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2012
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 8
    In: Cancer Research, American Association for Cancer Research (AACR), Vol. 70, No. 8_Supplement ( 2010-04-15), p. 4829-4829
    Abstract: Background: Coenzyme Q10 (CoQ10) is a component of the mitochondrial electron transport chain and is considered an important cellular antioxidant. Lower circulating CoQ10 levels are reported in patients with breast cancer, but epidemiologic evidence from large prospective studies is lacking. We examined the association of plasma CoQ10 levels with postmenopausal breast cancer risk in prospectively collected blood samples. Methods: Plasma levels of total CoQ10 were measured by HPLC with UV detection after precolumn coulometric oxidation among 160 incident postmenopausal breast cancer cases and 289 controls in the Multiethnic Cohort Study. Cases and controls were individually-matched on age, sex, ethnicity, study location (Hawaii or California), hormone replacement therapy use, date/time of collection and hours of fasting. Conditional logistic regression was used to compute odds ratios (ORs) and 95% confidence intervals (CIs). Results: Plasma CoQ10 levels were positively associated with breast cancer risk among postmenopausal women in the current study. The OR for the highest versus the lowest tertile was 1.6 (95% CI: 1.0 - 2.6; P = 0.05). The strongest association was observed for postmenopausal women under age 60 (OR for the highest versus the lowest tertile: 3.9; 95% CI: 1.1 - 14.0). Results were similar after adjusting for breast cancer risk factors. Conclusions: Higher CoQ10 levels in postmenopausal women are associated with increased breast cancer risk in this multiethnic population. Future studies are needed to define the origin of circulating CoQ10, its physiological meaning, and potential role in cancer etiology and progression. This work was supported by NIH Grants CA132149, CA33619. One of the authors (WC) was supported by NIH Training Grant CA90956. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 101st Annual Meeting of the American Association for Cancer Research; 2010 Apr 17-21; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2010;70(8 Suppl):Abstract nr 4829.
    Type of Medium: Online Resource
    ISSN: 0008-5472 , 1538-7445
    RVK:
    RVK:
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2010
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    detail.hit.zdb_id: 1432-1
    detail.hit.zdb_id: 410466-3
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  • 9
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 23, No. 11 ( 2014-11-01), p. 2568-2578
    Abstract: Background: Multiple primary cancers account for approximately 16% of all incident cancers in the United States. Although genome-wide association studies (GWAS) have identified many common genetic variants associated with various cancer sites, no study has examined the association of these genetic variants with risk of multiple primary cancers (MPC). Methods: As part of the National Human Genome Research Institute (NHGRI) Population Architecture using Genomics and Epidemiology (PAGE) study, we used data from the Multiethnic Cohort (MEC) and Women's Health Initiative (WHI). Incident MPC (IMPC) cases (n = 1,385) were defined as participants diagnosed with more than one incident cancer after cohort entry. Participants diagnosed with only one incident cancer after cohort entry with follow-up equal to or longer than IMPC cases served as controls (single-index cancer controls; n = 9,626). Fixed-effects meta-analyses of unconditional logistic regression analyses were used to evaluate the associations between 188 cancer risk variants and IMPC risk. To account for multiple comparisons, we used the false-positive report probability (FPRP) to determine statistical significance. Results: A nicotine dependence–associated and lung cancer variant, CHRNA3 rs578776 [OR, 1.16; 95% confidence interval (CI), 1.05–1.26; P = 0.004], and two breast cancer variants, EMBP1 rs11249433 and TOX3 rs3803662 (OR, 1.16; 95% CI, 1.04–1.28; P = 0.005 and OR, 1.13; 95% CI, 1.03–1.23; P = 0.006), were significantly associated with risk of IMPC. The associations for rs578776 and rs11249433 remained (P & lt; 0.05) after removing subjects who had lung or breast cancers, respectively (P ≤ 0.046). These associations did not show significant heterogeneity by smoking status (Pheterogeneity ≥ 0.53). Conclusions: Our study has identified rs578776 and rs11249433 as risk variants for IMPC. Impact: These findings may help to identify genetic regions associated with IMPC risk. Cancer Epidemiol Biomarkers Prev; 23(11); 2568–78. ©2014 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2014
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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  • 10
    Online Resource
    Online Resource
    American Association for Cancer Research (AACR) ; 2016
    In:  Cancer Epidemiology, Biomarkers & Prevention Vol. 25, No. 6 ( 2016-06-01), p. 1001-1003
    In: Cancer Epidemiology, Biomarkers & Prevention, American Association for Cancer Research (AACR), Vol. 25, No. 6 ( 2016-06-01), p. 1001-1003
    Abstract: Background: Mitochondria are involved in many processes that are central to the life and death of a cell. Oxidative phosphorylation (OXPHOS), in particular, is known to be altered in carcinogenesis, leading to an increase in the production of reactive oxidative species and glycolysis, one of the hallmarks of cancer cells. Because of this, genetic variation in the mitochondrial genome, which encodes for part of the OXPHOS pathway, has been suggested to play a role in many cancers, including prostate cancer. Methods: We comprehensively examined the role of the mitochondrial genome and prostate cancer risk in 4,086 prostate cancer cases and 3,698 controls from the Multiethnic Cohort (MEC), testing 350 mitochondrial SNPs (mtSNPs) in five racial/ethnic populations—Africans, Asian Americans, Europeans, Latinos, and Native Hawaiians. Logistic regression was conducted to examine single mitochondrial SNP and haplogroup associations. The sequence kernel association test was conducted for gene and pathway analysis. Results: Eleven mtSNPs and haplogroup N were nominally associated with overall prostate cancer risk at P & lt; 0.05. The mitochondrial DNA-encoded OXPHOS pathway, complexes, and genes were not associated with prostate cancer risk. No significant associations were identified after multiple testing corrections (all FDR q & gt; 0.20). Conclusions: The mitochondrial genome was not associated with prostate cancer risk in our study of 7,784 subjects from the MEC. Impact: Our comprehensive study does not support the role of the mitochondrial genome in the risk of prostate cancer. Cancer Epidemiol Biomarkers Prev; 25(6); 1001–3. ©2016 AACR.
    Type of Medium: Online Resource
    ISSN: 1055-9965 , 1538-7755
    Language: English
    Publisher: American Association for Cancer Research (AACR)
    Publication Date: 2016
    detail.hit.zdb_id: 2036781-8
    detail.hit.zdb_id: 1153420-5
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