Association of birth weight with cancer risk: a dose–response meta-analysis and Mendelian randomization study

Chen, Chao; Chen, Xiaoying; Wu, Donghong; Wang, Huanting; Wang, Chuqiao; Shen, Jieni; An, Yiran; Zhong, Ran; Li, Caichen; Liang, Wenhua

doi:10.1007/s00432-022-04171-2

Cited by 6 publications

(2 citation statements)

References 74 publications

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“…However, it showed only a trend towards association in the multi-ancestry analysis (OR 0.88, P value 0.16). This variant maps near multiple GWAS hits for hip-to-waist ratio [93] and birth weight [94][95][96]; both of which are phenotypes associated with increased breast cancer risk [97][98][99] but has not been associated with risk in women of European, African, or East Asian descent [100].…”

Section: Germline Variants Associated With Pik3ca Mutations and Impac...mentioning

confidence: 99%

Association ofESR1germline variants withTP53somatic variants in breast tumors in a genome-wide study

Tjader,

Beer,

Ramroop

et al. 2023

Preprint

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BackgroundIn breast tumors, somatic mutation frequencies inTP53andPIK3CAvary by tumor subtype and ancestry. HER2 positive and triple negative breast cancers (TNBC) have a higher frequency ofTP53somatic mutations than other subtypes.PIK3CAmutations are more frequently observed in hormone receptor positive tumors. Emerging data suggest tumor mutation status is associated with germline variants and genetic ancestry. We aimed to identify germline variants that are associated with somaticTP53orPIK3CAmutation status in breast tumors.MethodsA genome-wide association study was conducted using breast cancer mutation status ofTP53andPIK3CAand functional mutation categories includingTP53gain of function (GOF) and loss of function mutations andPIK3CAactivating/hotspot mutations. The discovery analysis consisted of 2850 European ancestry women from three datasets. Germline variants showing evidence of association with somatic mutations were selected for validation analyses based on predicted function, allele frequency, and proximity to known cancer genes or risk loci. Candidate variants were assessed for association with mutation status in a multi-ancestry validation study, a Malaysian study, and a study of African American/Black women with TNBC.ResultsThe discovery Germline x Mutation (GxM) association study found five variants associated with one or moreTP53phenotypes withPvalues <1×10-6, 33 variants associated with one or moreTP53phenotypes withPvalues <1×10-5, and 44 variants associated with one or morePIK3CAphenotypes withPvalues <1×10-5. In the multi-ancestry and Malaysian validation studies, germlineESR1locus variant, rs9383938, was associated with the presence ofTP53mutations overall (Pvalues 6.8×10-5and 9.8×10-8, respectively) andTP53GOF mutations (Pvalue 8.4×10-6). Multiple variants showed suggestive evidence of association withPIK3CAmutation status in the validation studies, but none were significant after correction for multiple comparisons.ConclusionsWe found evidence that germline variants were associated withTP53andPIK3CAmutation status in breast cancers. Variants near the estrogen receptor alpha gene,ESR1,were significantly associated with overallTP53mutations and GOF mutations. Larger multi-ancestry studies are needed to confirm these findings and determine if these variants contribute to ancestry-specific differences in mutation frequency.

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Section: Germline Variants Associated With Pik3ca Mutations and Impac...mentioning

confidence: 99%

Association ofESR1germline variants withTP53somatic variants in breast tumors in a genome-wide study

Tjader,

Beer,

Ramroop

et al. 2023

Preprint

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“…They also noted that the existence of a causal relationship has not been adequately demonstrated due to susceptibility to unmeasured confounders. Indeed, while previous epidemiological studies have demonstrated strong associations between various risk factors and diseases, subsequent research has revealed that these associations are often the result of interference from residual confounders rather than direct causation.Some typical examples include sex hormone-related traits, systemic lupus erythematosus (SLE), and vitamin D and digestive cancers [12][13] . With the recent increase in the availability of genome-wide association study (GWAS) databases, Mendelian randomization (MR) has utilized genetic variants strongly correlated with exposure factors as instrumental variables to evaluate causal relationships between exposure factors and outcomes.…”

Section: Introductionmentioning

confidence: 99%

Age-related hearing loss and dementia risk causality: two-way Mendelian randomization analysis

Tian,

Leng,

Wang

et al. 2024

Preprint

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In response to the ongoing debate in clinical studies about the relationship between age-related hearing impairment and dementia, a two-sample Mendelian randomization (MR) study using a genome-wide association study (GWAS) database was conducted to elucidate the genetic effects of age-related hearing loss on four types of dementia (dementia, vascular dementia, and Parkinson's dementia，Alzheimer's disease).MR analyzed data from two independent sources on age-related hearing loss (exposure) and four dementias (outcome). We used the inverse variance weighting (IVW) method, the MR Egger method, and the weighted median (WM) method to investigate the impact of age-related hearing loss on dementia.In addition, we analyzed heterogeneity, horizontal diversity, and stability through Cochran's Q-test, MR-Egger intercept, and leave-one-out sensitivity analysis, respectively.Age-related hearing loss was associated with dementia (OR=1.054, 95% CI:0.633-1.754, P=0.840), vascular dementia (OR=1.985, 95% CI:0.550-7.169), P=0.295), Parkinson's dementia (OR=2.263, 95% CI:0.235-21.774, P=0.480), andAlzheimer's disease (OR=1.001, 95% CI:0.999-1.004, P=0.392), but no causal effect was found.The results of our study indicate that there is no statistically significant responsible association between age-related hearing loss and any of the four dementias, in accordance to our two-sample MR analysis.

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2024

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Association of birth weight with cancer risk: a dose–response meta-analysis and Mendelian randomization study

Cited by 6 publications

References 74 publications

Association ofESR1germline variants withTP53somatic variants in breast tumors in a genome-wide study

Association ofESR1germline variants withTP53somatic variants in breast tumors in a genome-wide study

Age-related hearing loss and dementia risk causality: two-way Mendelian randomization analysis

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