scholarly journals Letter regarding article, “Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis”

2019 ◽  
Vol 48 (3) ◽  
pp. 1014-1015 ◽  
Author(s):  
Vanessa Y Tan ◽  
James Yarmolinsky ◽  
Debbie A Lawlor ◽  
Nicholas J Timpson
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Mendelian Randomization ◽  
Mendelian Randomization Analysis ◽  
Randomization Analysis

scholarly journals A Mendelian randomization analysis of circulating lipid traits and breast cancer risk

2019 ◽  
Vol 49 (4) ◽  
pp. 1117-1131 ◽  
Author(s):  
Alicia Beeghly-Fadiel ◽  
Nikhil K Khankari ◽  
Ryan J Delahanty ◽  
Xiao-Ou Shu ◽  
Yingchang Lu ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Standard Deviation ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Total Cholesterol ◽  
Mendelian Randomization ◽  
Density Lipoprotein ◽  
Sensitivity Analyses ◽  
Standard Deviation Increase ◽  
Randomization Analysis

Abstract Background Conventional epidemiologic studies have evaluated associations between circulating lipid levels and breast cancer risk, but results have been inconsistent. As Mendelian randomization analyses may provide evidence for causal inference, we sought to evaluate potentially unbiased associations between breast cancer risk and four genetically predicted lipid traits. Methods Previous genome-wide association studies (GWAS) have identified 164 discrete variants associated with high density lipoprotein-cholesterol (HDL-C), low density lipoprotein-cholesterol (LDL-C), triglycerides and total cholesterol. We used 162 of these unique variants to construct weighted genetic scores (wGSs) for a total of 101 424 breast cancer cases and 80 253 controls of European ancestry from the Breast Cancer Association Consortium (BCAC). Unconditional logistic regression was used to estimate odds ratios (OR) and 95% confidence intervals (CI) for associations between per standard deviation increase in genetically predicted lipid traits and breast cancer risk. Additional Mendelian randomization analysis approaches and sensitivity analyses were conducted to assess pleiotropy and instrument validity. Results Corresponding to approximately 15 mg/dL, one standard deviation increase in genetically predicted HDL-C was associated with a 12% increased breast cancer risk (OR: 1.12, 95% CI: 1.08–1.16). Findings were consistent after adjustment for breast cancer risk factors and were robust in several sensitivity analyses. Associations with genetically predicted triglycerides and total cholesterol were inconsistent, and no association for genetically predicted LDL-C was observed. Conclusions This study provides strong evidence that circulating HDL-C may be associated with an increased risk of breast cancer, whereas LDL-C may not be related to breast cancer risk.

scholarly journals Height and Body Mass Index as Modifiers of Breast Cancer Risk in BRCA1/2 Mutation Carriers: A Mendelian Randomization Study

2018 ◽  
Vol 111 (4) ◽  
pp. 350-364 ◽  
Author(s):  
Frank Qian ◽  
Shengfeng Wang ◽  
Jonathan Mitchell ◽  
Lesley McGuffog ◽  
Daniel Barrowdale ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Mass Index ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Body Mass ◽  
Mendelian Randomization ◽  
Mutation Carriers

scholarly journals Circulating Selenium and Prostate Cancer Risk: A Mendelian Randomization Analysis

2018 ◽  
Vol 110 (9) ◽  
pp. 1035-1038 ◽  
Author(s):  
James Yarmolinsky ◽  
Carolina Bonilla ◽  
Philip C Haycock ◽  
Ryan J Q Langdon ◽  
Luca A Lotta ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cancer Risk ◽  
Mendelian Randomization ◽  
Prostate Cancer Risk ◽  
Mendelian Randomization Analysis ◽  
Randomization Analysis

scholarly journals Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis

2018 ◽  
Vol 48 (3) ◽  
pp. 795-806 ◽  
Author(s):  
Xiang Shu ◽  
Lang Wu ◽  
Nikhil K Khankari ◽  
Xiao-Ou Shu ◽  
Thomas J Wang ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Type 2 Diabetes ◽  
Estrogen Receptor ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Mendelian Randomization ◽  
Menopausal Status ◽  
Inverse Association ◽  
Fasting Insulin

Abstract Background In addition to the established association between general obesity and breast cancer risk, central obesity and circulating fasting insulin and glucose have been linked to the development of this common malignancy. Findings from previous studies, however, have been inconsistent, and the nature of the associations is unclear. Methods We conducted Mendelian randomization analyses to evaluate the association of breast cancer risk, using genetic instruments, with fasting insulin, fasting glucose, 2-h glucose, body mass index (BMI) and BMI-adjusted waist-hip-ratio (WHRadj BMI). We first confirmed the association of these instruments with type 2 diabetes risk in a large diabetes genome-wide association study consortium. We then investigated their associations with breast cancer risk using individual-level data obtained from 98 842 cases and 83 464 controls of European descent in the Breast Cancer Association Consortium. Results All sets of instruments were associated with risk of type 2 diabetes. Associations with breast cancer risk were found for genetically predicted fasting insulin [odds ratio (OR) = 1.71 per standard deviation (SD) increase, 95% confidence interval (CI) = 1.26-2.31, p  =  5.09  ×  10–4], 2-h glucose (OR = 1.80 per SD increase, 95% CI = 1.3 0-2.49, p  =  4.02  ×  10–4), BMI (OR = 0.70 per 5-unit increase, 95% CI = 0.65-0.76, p  =  5.05  ×  10–19) and WHRadj BMI (OR = 0.85, 95% CI = 0.79-0.91, p  =  9.22  ×  10–6). Stratified analyses showed that genetically predicted fasting insulin was more closely related to risk of estrogen-receptor [ER]-positive cancer, whereas the associations with instruments of 2-h glucose, BMI and WHRadj BMI were consistent regardless of age, menopausal status, estrogen receptor status and family history of breast cancer. Conclusions We confirmed the previously reported inverse association of genetically predicted BMI with breast cancer risk, and showed a positive association of genetically predicted fasting insulin and 2-h glucose and an inverse association of WHRadj BMI with breast cancer risk. Our study suggests that genetically determined obesity and glucose/insulin-related traits have an important role in the aetiology of breast cancer.

scholarly journals Appraising the role of previously reported risk factors in epithelial ovarian cancer risk: A Mendelian randomization analysis

PLoS Medicine ◽  
2019 ◽  
Vol 16 (8) ◽  
pp. e1002893 ◽  
Author(s):  
James Yarmolinsky ◽  
Caroline L. Relton ◽  
Artitaya Lophatananon ◽  
Kenneth Muir ◽  
Usha Menon ◽  
...  
Keyword(s):  
Risk Factors ◽  
Ovarian Cancer ◽  
Cancer Risk ◽  
Epithelial Ovarian Cancer ◽  
Mendelian Randomization ◽  
Ovarian Cancer Risk ◽  
Mendelian Randomization Analysis ◽  
Randomization Analysis

scholarly journals Coffee consumption and risk of breast cancer: a Mendelian Randomization study

2020 ◽  
Author(s):  
Merete Ellingjord-Dale ◽  
Nikos Papadimitriou ◽  
Michalis Katsoulis ◽  
Chew Yee ◽  
Niki Dimou ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Random Effects ◽  
Mendelian Randomization ◽  
Coffee Consumption ◽  
Sensitivity Analyses ◽  
European Ancestry ◽  
Inverse Association ◽  
Er Positive

AbstractBackgroundObservational studies have reported either null or weak protective associations for coffee consumption and risk of breast cancer.MethodsWe conducted a two-sample Mendelian randomization randomization (MR) analysis to evaluate the relationship between coffee consumption and breast cancer risk using 33 single-nucleotide polymorphisms (SNPs) associated with coffee consumption from a genome-wide association (GWA) study on 212,119 female UK Biobank participants of White British ancestry. Risk estimates for breast cancer were retrieved from publicly available GWA summary statistics from the Breast Cancer Association Consortium (BCAC) on 122,977 cases (of which 69,501 were estrogen receptor (ER)-positive, 21,468 ER-negative) and 105,974 controls of European ancestry. Random-effects inverse variance weighted (IVW) MR analyses were performed along with several sensitivity analyses to assess the impact of potential MR assumption violations.ResultsOne cup per day increase in genetically predicted coffee consumption in women was not associated with risk of total (IVW random-effects; odds ratio (OR): 0.91, 95% confidence intervals (CI): 0.80-1.02, P: 0.12, P for instrument heterogeneity: 7.17e-13), ER-positive (OR=0.90, 95% CI: 0.79-1.02, P: 0.09) and ER-negative breast cancer (OR: 0.88, 95% CI: 0.75-1.03, P: 0.12). Null associations were also found in the sensitivity analyses using MR-Egger (total breast cancer; OR: 1.00, 95% CI: 0.80-1.25), weighted median (OR: 0.97, 95% CI: 0.89-1.05) and weighted mode (OR: 1.00, CI: 0.93-1.07).ConclusionsThe results of this large MR study do not support an association of genetically predicted coffee consumption on breast cancer risk, but we cannot rule out existence of a weak inverse association.

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