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  1. Article ; Online: Age at Menarche, age at Natural Menopause, and Risk of Lung and Colorectal Cancers: A Mendelian Randomization Study.

    Denos, Marion / Sun, Yi-Qian / Jiang, Lin / Brumpton, Ben Michael / Mai, Xiao-Mei

    Journal of the Endocrine Society

    2023  Volume 7, Issue 8, Page(s) bvad077

    Abstract: Background: The roles of age at menarche and age at menopause in the etiology of lung and colorectal cancers are unclear.: Objective: We aimed to investigate potential causal associations between age at menarche, age at natural menopause, and risk of ...

    Abstract Background: The roles of age at menarche and age at menopause in the etiology of lung and colorectal cancers are unclear.
    Objective: We aimed to investigate potential causal associations between age at menarche, age at natural menopause, and risk of lung and colorectal cancers using a Mendelian randomization (MR) approach.
    Methods: From the Trøndelag Health Study in Norway, we defined two cohorts of 35 477 and 17 118 women to study the effects of age at menarche and age at natural menopause, respectively. We ran univariable MR to evaluate the potential causal associations. We performed multivariable MR adjusting for genetic variants of adult body mass index (BMI) to estimate the direct effect of age at menarche.
    Results: Genetically predicted 1-year increase in age at menarche was associated with a lower risk of lung cancer overall (hazard ratio [HR, 0.64; 95% CI, 0.48-0.86), lung adenocarcinoma (HR, 0.61; 95% CI, 0.38-0.99), and lung non-adenocarcinoma (HR, 0.66; 95% CI, 0.45-0.95). After adjusting for adult BMI using a multivariable MR model, the direct effect estimates reduced to HR 0.72 (95% CI, 0.54-0.95) for lung cancer overall, HR 0.67 (95% CI, 0.43-1.03) for lung adenocarcinoma, and HR 0.77 (95% CI, 0.54-1.09) for lung non-adenocarcinoma. Age at menarche was not associated with colorectal cancer. Moreover, genetically predicted age at natural menopause was not associated with lung and colorectal cancers.
    Conclusion: Our MR study suggested that later age at menarche was causally associated with a decreased risk of lung cancer overall and its subtypes, and adult BMI might be a mediator.
    Language English
    Publishing date 2023-06-07
    Publishing country United States
    Document type Journal Article
    ISSN 2472-1972
    ISSN (online) 2472-1972
    DOI 10.1210/jendso/bvad077
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Reproductive Factors in Relation to Incidence of Lung and Colorectal Cancers in a Cohort of Norwegian Women: The HUNT Study.

    Denos, Marion / Sun, Yi-Qian / Brumpton, Ben Michael / Langhammer, Arnulf / Chen, Yue / Mai, Xiao-Mei

    Journal of the Endocrine Society

    2022  Volume 7, Issue 1, Page(s) bvac175

    Abstract: Context: The roles of reproductive factors in the etiology of lung and colorectal cancers, among the most common cancers in women, are unclear.: Objective: We aimed to explore whether female reproductive factors were associated with the incidence of ... ...

    Abstract Context: The roles of reproductive factors in the etiology of lung and colorectal cancers, among the most common cancers in women, are unclear.
    Objective: We aimed to explore whether female reproductive factors were associated with the incidence of lung and colorectal cancers.
    Methods: We followed up 33 314 cancer-free women who participated in the HUNT Study in Norway from 1995-1997 to 2018. A large panel of reproductive factors were self-reported at baseline. Incident lung and colorectal cancer cases were ascertained from the Cancer Registry of Norway. Cox regression models were used to estimate hazard ratios (HRs) with 95% CIs after adjustment for important confounders.
    Results: During a median follow-up interval of 22.2 years, 467 women developed lung cancer (including 169 lung adenocarcinoma), 660 developed colon cancer, and 211 had rectal cancer. Early menarche (≤12 years) was associated with an increased incidence of lung adenocarcinoma (HR 1.43; 95% CI, 1.02-2.03). Women with one or no child had an increased colon cancer incidence (HR 1.26; 95% CI, 1.03-1.54). Hormone therapy appeared to be associated with a decreased incidence of rectal cancer (HR 0.68; 95% CI, 0.44-1.04). Results in the subgroup of postmenopausal women were similar or strengthened. Other reproductive factors were not related to the risk of lung, colon, and rectal cancers.
    Conclusion: Certain reproductive factors might play a role in the etiology of lung and colorectal cancers. Further investigations are warranted to study if they are causal associations.
    Language English
    Publishing date 2022-11-12
    Publishing country United States
    Document type Journal Article
    ISSN 2472-1972
    ISSN (online) 2472-1972
    DOI 10.1210/jendso/bvac175
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article: Sex hormones and risk of lung and colorectal cancers in women: a Mendelian randomization study.

    Denos, Marion / Sun, Yi-Qian / Brumpton, Ben / Li, Yafang / Albanes, Demetrius / Burnett-Hartman, Andrea / Campbell, Peter T / Küry, Sébastien / Li, Christopher I / White, Emily / Samadder, Jewel N / Jenkins, Mark / Mai, Xiao-Mei

    Research square

    2024  

    Abstract: The roles of sex hormones such as estradiol, testosterone, and sex hormone-binding globulin (SHBG) in the etiology of lung and colorectal cancers in women, among the most common cancers after breast cancer, are unclear. This Mendelian randomization (MR) ... ...

    Abstract The roles of sex hormones such as estradiol, testosterone, and sex hormone-binding globulin (SHBG) in the etiology of lung and colorectal cancers in women, among the most common cancers after breast cancer, are unclear. This Mendelian randomization (MR) study evaluated such potential causal associations in women of European ancestry. We used summary statistics data from genome-wide association studies (GWASs) on sex hormones and from the Trøndelag Health (HUNT) Study and large consortia on cancers. There was suggestive evidence of genetically predicted 1-standard deviation increase in total testosterone levels being associated with a lower risk of lung non-adenocarcinoma (hazard ratio (HR) 0.60, 95% CI 0.37-0.98) in the HUNT Study. However, this was not confirmed by using data from a larger consortium. In general, we did not find convincing evidence to support a causal role of sex hormones on risk of lung and colorectal cancers in women of European ancestry.
    Language English
    Publishing date 2024-04-10
    Publishing country United States
    Document type Preprint
    DOI 10.21203/rs.3.rs-4083598/v1
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: Vitamin D status and risk of type 2 diabetes in the Norwegian HUNT cohort study: does family history or genetic predisposition modify the association?

    Denos, Marion / Mai, Xiao-Mei / Åsvold, Bjørn Olav / Sørgjerd, Elin Pettersen / Chen, Yue / Sun, Yi-Qian

    BMJ open diabetes research & care

    2021  Volume 9, Issue 1

    Abstract: Introduction: We sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study (HUNT), and the possible effect ... ...

    Abstract Introduction: We sought to investigate the relationship between serum 25-hydroxyvitamin D (25(OH)D) level and the risk of type 2 diabetes mellitus (T2DM) in adults who participated in the Trøndelag Health Study (HUNT), and the possible effect modification by family history and genetic predisposition.
    Research design and methods: This prospective study included 3574 diabetes-free adults at baseline who participated in the HUNT2 (1995-1997) and HUNT3 (2006-2008) surveys. Serum 25(OH)D levels were determined at baseline and classified as <50 and ≥50 nmol/L. Family history of diabetes was defined as self-reported diabetes among parents and siblings. A Polygenic Risk Score (PRS) for T2DM based on 166 single-nucleotide polymorphisms was generated. Incident T2DM was defined by self-report and/or non-fasting glucose levels greater than 11 mmol/L and serum glutamic acid decarboxylase antibody level of <0.08 antibody index at the follow-up. Multivariable logistic regression models were applied to calculate adjusted ORs with 95% CIs. Effect modification by family history or PRS was assessed by likelihood ratio test (LRT).
    Results: Over 11 years of follow-up, 92 (2.6%) participants developed T2DM. A higher risk of incident T2DM was observed in participants with serum 25(OH)D level of<50 nmol/L compared with those of ≥50 nmol/L (OR 1.72, 95% CI 1.03 to 2.86). Level of 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in adults without family history of diabetes (OR 3.87, 95% CI 1.62 to 9.24) but not in those with a family history (OR 0.72, 95% CI 0.32 to 1.62, p value for LRT=0.003). There was no effect modification by PRS (p value for LRT>0.23).
    Conclusion: Serum 25(OH)D<50 nmol/L was associated with an increased risk of T2DM in Norwegian adults. The inverse association was modified by family history of diabetes but not by genetic predisposition to T2DM.
    MeSH term(s) Adult ; Cohort Studies ; Diabetes Mellitus, Type 2/epidemiology ; Diabetes Mellitus, Type 2/genetics ; Genetic Predisposition to Disease ; Humans ; Incidence ; Norway/epidemiology ; Prospective Studies ; Risk Factors ; Vitamin D
    Chemical Substances Vitamin D (1406-16-2)
    Language English
    Publishing date 2021-01-05
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't
    ZDB-ID 2732918-5
    ISSN 2052-4897 ; 2052-4897
    ISSN (online) 2052-4897
    ISSN 2052-4897
    DOI 10.1136/bmjdrc-2020-001948
    Database MEDical Literature Analysis and Retrieval System OnLINE

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