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  1. Article ; Online: Association between Airport Ultrafine Particles and Lung Cancer Risk: The Multiethnic Cohort Study.

    Bookstein, Arthur / Po, Justine / Tseng, Chiuchen / Larson, Timothy V / Yang, Juan / Park, Sung-Shim L / Wu, Jun / Shariff-Marco, Salma / Inamdar, Pushkar P / Ihenacho, Ugonna / Setiawan, Veronica Wendy / DeRouen, Mindy C / Le Marchand, Loïc / Stram, Daniel O / Samet, Jonathan / Ritz, Beate / Fruin, Scott / Wu, Anna H / Cheng, Iona

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

    2024  

    Abstract: Background: Ultrafine particles (UFPs) are unregulated air pollutants abundant in aviation exhaust. Emerging evidence suggests that UFPs may impact lung health due to their high surface area-to-mass ratio and deep penetration into airways. This study ... ...

    Abstract Background: Ultrafine particles (UFPs) are unregulated air pollutants abundant in aviation exhaust. Emerging evidence suggests that UFPs may impact lung health due to their high surface area-to-mass ratio and deep penetration into airways. This study aimed to assess long-term exposure to airport-related UFPs and lung cancer incidence in a multiethnic population in Los Angeles County.
    Methods: Within the California Multiethnic Cohort, we examined the association between long-term exposure to airport-related UFPs and lung cancer incidence. Multivariable Cox proportional hazards regression models were used to estimate the effect of UFP exposure on lung cancer incidence. Subgroup analyses by demographics, histology and smoking status were conducted.
    Results: Airport-related UFP exposure was not associated with lung cancer risk [per one IGR HR = 1.01, 95% CI: 0.97-1.05] overall and across race/ethnicity. A suggestive positive association was observed between a one IQR increase in UFP exposure and lung squamous cell carcinoma (SCC) risk [HR = 1.08, 95% CI: 1.00-1.17] with a Phet for histology=0.05. Positive associations were observed in 5-year lag analysis for SCC [HR = 1.12, CI: 1.02-1.22] and large cell carcinoma risk [HR = 1.23, CI: 1.01-1.49] with a [Phet for histology = 0.01].
    Conclusions: This large prospective cohort analysis suggests a potential association between airport-related UFP exposure and specific lung histologies. The findings align with research indicating that UFPs found in aviation exhaust may induce inflammatory and oxidative injury leading to SCC.
    Impact: These results highlight the potential role of airport-related UFP exposure in the development of lung SCC.
    Language English
    Publishing date 2024-02-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1153420-5
    ISSN 1538-7755 ; 1055-9965
    ISSN (online) 1538-7755
    ISSN 1055-9965
    DOI 10.1158/1055-9965.EPI-23-0924
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3693: Show issues Location:
    Je nach Verfügbarkeit (siehe Angabe bei Bestand)
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    Jg. 1995 - 2021: Lesesall (2.OG)
    ab Jg. 2022: Lesesaal (EG)

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  2. Article ; Online: Nicotine N-glucuronidation relative to N-oxidation and C-oxidation and UGT2B10 genotype in five ethnic/racial groups.

    Murphy, Sharon E / Park, Sung-Shim L / Thompson, Elizabeth F / Wilkens, Lynne R / Patel, Yesha / Stram, Daniel O / Le Marchand, Loic

    Carcinogenesis

    2014  Volume 35, Issue 11, Page(s) 2526–2533

    Abstract: Nicotine metabolism influences smoking behavior and differences in metabolism probably contribute to ethnic variability in lung cancer risk. We report here on the proportion of nicotine metabolism by cytochrome P450 2A6-catalyzed C-oxidation, UDP- ... ...

    Abstract Nicotine metabolism influences smoking behavior and differences in metabolism probably contribute to ethnic variability in lung cancer risk. We report here on the proportion of nicotine metabolism by cytochrome P450 2A6-catalyzed C-oxidation, UDP-glucuronosyl transferase 2B10 (UGT2B10)-catalyzed N-glucuronidation and flavin monooxygenase 3-catalyzed N-oxidation in five ethnic/racial groups and the role of UGT2B10 genotype on the metabolic patterns observed. Nicotine and its metabolites were quantified in urine from African American (AA, n = 364), Native Hawaiian (NH, n = 311), White (n = 437), Latino (LA, n = 453) and Japanese American (JA, n = 674) smokers. Total nicotine equivalents, the sum of nicotine and six metabolites, and nicotine metabolism phenotypes were calculated. The relationship of UGT2B10 genotype to nicotine metabolic pathways was determined for each group; geometric means were computed and adjusted for age, sex, creatinine, and body mass index. Nicotine metabolism patterns were unique across the groups, C-oxidation was lowest in JA and NH (P < 0.0001), and N-glucuronidation lowest in AA (P < 0.0001). There was no difference in C-oxidation among Whites and AA and LA. Nicotine and cotinine glucuronide ratios were 2- and 3-fold lower in AA compared with Whites. Two UGT variants, a missense mutation (Asp67Tyr, rs61750900) and a splice variant (rs116294140) accounted for 33% of the variation in glucuronidation. In AA, the splice variant accounted for the majority of the reduced nicotine glucuronidation. UGT2B10 variant allele carriers had increased levels of C-oxidation (P = 0.0099). Our data indicate that the relative importance of nicotine metabolic pathways varies by ethnicity, and all pathways should be considered when characterizing the role of nicotine metabolism on smoking behavior and cancer risk.
    MeSH term(s) Adolescent ; Adult ; Ethnic Groups/genetics ; Female ; Genotype ; Glucuronates/genetics ; Glucuronosyltransferase/genetics ; Glucuronosyltransferase/pharmacokinetics ; Hepatocytes/metabolism ; Humans ; Male ; Microsomes, Liver/drug effects ; Microsomes, Liver/metabolism ; Middle Aged ; Neoplasms/genetics ; Neoplasms/metabolism ; Neoplasms/pathology ; Nicotine/analogs & derivatives ; Nicotine/genetics ; Nicotine/metabolism ; Risk Factors ; Smoking/genetics
    Chemical Substances Glucuronates ; nicotine N-glucuronide (152306-59-7) ; Nicotine (6M3C89ZY6R) ; UGT2B10 protein, human (EC 2.4.1.-) ; Glucuronosyltransferase (EC 2.4.1.17)
    Language English
    Publishing date 2014-09-18
    Publishing country England
    Document type Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural
    ZDB-ID 603134-1
    ISSN 1460-2180 ; 0143-3334
    ISSN (online) 1460-2180
    ISSN 0143-3334
    DOI 10.1093/carcin/bgu191
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    Zs.A 1558: Show issues Location:
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  3. Article ; Online: The contribution of common genetic variation to nicotine and cotinine glucuronidation in multiple ethnic/racial populations.

    Patel, Yesha M / Stram, Daniel O / Wilkens, Lynne R / Park, Sung-Shim L / Henderson, Brian E / Le Marchand, Loic / Haiman, Christopher A / Murphy, Sharon E

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

    2014  Volume 24, Issue 1, Page(s) 119–127

    Abstract: Background: The lung cancer risk of smokers varies by race/ethnicity even after adjustment for smoking. Evaluating the role of genetics in nicotine metabolism is likely important in understanding these differences, as disparities in risk may be related ... ...

    Abstract Background: The lung cancer risk of smokers varies by race/ethnicity even after adjustment for smoking. Evaluating the role of genetics in nicotine metabolism is likely important in understanding these differences, as disparities in risk may be related to differences in nicotine dose and metabolism.
    Methods: We conducted a genome-wide association study in search of common genetic variants that predict nicotine and cotinine glucuronidation in a sample of 2,239 smokers (437 European Americans, 364 African Americans, 453 Latinos, 674 Japanese Americans, and 311 Native Hawaiians) in the Multiethnic Cohort Study. Urinary concentration of nicotine and its metabolites were determined.
    Results: Among 11,892,802 variants analyzed, 1,241 were strongly associated with cotinine glucuronidation, 490 of which were also associated with nicotine glucuronidation (P < 5×10(-8)). The vast majority were within chromosomal region 4q13, near UGT2B10. Fifteen independent and globally significant SNPs explained 33.2% of the variation in cotinine glucuronidation, ranging from 55% for African Americans to 19% for Japanese Americans. The strongest single SNP association was for rs115765562 (P = 1.60 × 10(-155)). This SNP is highly correlated with a UGT2B10 splice site variant, rs116294140, which together with rs6175900 (Asp67Tyr) explains 24.3% of the variation. The top SNP for nicotine glucuronidation (rs116224959, P = 2.56 × 10(-43)) was in high LD (r(2) = 0.99) with rs115765562.
    Conclusions: Genetic variation in UGT2B10 contributes significantly to nicotine and cotinine glucuronidation but not to nicotine dose.
    Impact: The contribution of genetic variation to nicotine and cotinine glucuronidation varies significantly by racial/ethnic group, but is unlikely to contribute directly to lung cancer risk.
    MeSH term(s) Aged ; Ethnic Groups/genetics ; Female ; Genetic Variation ; Genome-Wide Association Study/methods ; Genotype ; Glucuronides/metabolism ; Humans ; Male ; Middle Aged ; Nicotine/metabolism ; Phenotype ; Polymorphism, Single Nucleotide ; Quality Control ; Smoking/genetics
    Chemical Substances Glucuronides ; Nicotine (6M3C89ZY6R)
    Language English
    Publishing date 2014-10-07
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural
    ZDB-ID 1153420-5
    ISSN 1538-7755 ; 1055-9965
    ISSN (online) 1538-7755
    ISSN 1055-9965
    DOI 10.1158/1055-9965.EPI-14-0815
    Database MEDical Literature Analysis and Retrieval System OnLINE

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    In stock of ZB MED Cologne/Königswinter

    Zs.A 3693: Show issues Location:
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    ab Jg. 2022: Lesesaal (EG)

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  4. Article ; Online: Genetic analyses of diverse populations improves discovery for complex traits.

    Wojcik, Genevieve L / Graff, Mariaelisa / Nishimura, Katherine K / Tao, Ran / Haessler, Jeffrey / Gignoux, Christopher R / Highland, Heather M / Patel, Yesha M / Sorokin, Elena P / Avery, Christy L / Belbin, Gillian M / Bien, Stephanie A / Cheng, Iona / Cullina, Sinead / Hodonsky, Chani J / Hu, Yao / Huckins, Laura M / Jeff, Janina / Justice, Anne E /
    Kocarnik, Jonathan M / Lim, Unhee / Lin, Bridget M / Lu, Yingchang / Nelson, Sarah C / Park, Sung-Shim L / Poisner, Hannah / Preuss, Michael H / Richard, Melissa A / Schurmann, Claudia / Setiawan, Veronica W / Sockell, Alexandra / Vahi, Karan / Verbanck, Marie / Vishnu, Abhishek / Walker, Ryan W / Young, Kristin L / Zubair, Niha / Acuña-Alonso, Victor / Ambite, Jose Luis / Barnes, Kathleen C / Boerwinkle, Eric / Bottinger, Erwin P / Bustamante, Carlos D / Caberto, Christian / Canizales-Quinteros, Samuel / Conomos, Matthew P / Deelman, Ewa / Do, Ron / Doheny, Kimberly / Fernández-Rhodes, Lindsay / Fornage, Myriam / Hailu, Benyam / Heiss, Gerardo / Henn, Brenna M / Hindorff, Lucia A / Jackson, Rebecca D / Laurie, Cecelia A / Laurie, Cathy C / Li, Yuqing / Lin, Dan-Yu / Moreno-Estrada, Andres / Nadkarni, Girish / Norman, Paul J / Pooler, Loreall C / Reiner, Alexander P / Romm, Jane / Sabatti, Chiara / Sandoval, Karla / Sheng, Xin / Stahl, Eli A / Stram, Daniel O / Thornton, Timothy A / Wassel, Christina L / Wilkens, Lynne R / Winkler, Cheryl A / Yoneyama, Sachi / Buyske, Steven / Haiman, Christopher A / Kooperberg, Charles / Le Marchand, Loic / Loos, Ruth J F / Matise, Tara C / North, Kari E / Peters, Ulrike / Kenny, Eimear E / Carlson, Christopher S

    Nature

    2019  Volume 570, Issue 7762, Page(s) 514–518

    Abstract: Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery efforts are based on data from populations of European ... ...

    Abstract Genome-wide association studies (GWAS) have laid the foundation for investigations into the biology of complex traits, drug development and clinical guidelines. However, the majority of discovery efforts are based on data from populations of European ancestry
    MeSH term(s) Asians/genetics ; Blacks/genetics ; Body Height/genetics ; Cohort Studies ; Female ; Genetics, Medical/methods ; Genome-Wide Association Study/methods ; Health Equity/trends ; Health Status Disparities ; Hispanic or Latino/genetics ; Humans ; Male ; Minority Groups ; Multifactorial Inheritance/genetics ; United States ; Women's Health
    Language English
    Publishing date 2019-06-19
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-019-1310-4
    Database MEDical Literature Analysis and Retrieval System OnLINE

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