scholarly journals Deciphering how early life adiposity influences breast cancer risk using Mendelian randomization

2021 ◽  
Author(s):  
Marina Vabistsevits ◽  
George Davey Smith ◽  
Eleanor Sanderson ◽  
Tom G Richardson ◽  
Bethan Lloyd-Lewis ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Size ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Protective Effect ◽  
Mendelian Randomization ◽  
Later Life ◽  
Age At Menarche ◽  
Systematic Exploration ◽  
Glycaemic Traits

Studies suggest that adiposity in childhood may reduce the risk of breast cancer in later life. The biological mechanism underlying this effect is unclear but is likely to be independent of body size in adulthood. Using a Mendelian randomization framework, we investigated 18 hypothesised mediators of the protective effect of childhood adiposity on later-life breast cancer, including hormonal, reproductive, physical, and glycaemic traits. Our results indicate that, while most of the hypothesised mediators are affected by childhood body size, only IGF-1, testosterone, age at menarche and age at menopause influenced breast cancer risk. However, accounting for those traits in multivariable Mendelian randomization showed that the protective effect of childhood body size still remained. This suggests either a direct effect of childhood body size on breast cancer risk or mediation via other pathways not considered. Our work presents a framework for the systematic exploration of potential biological mediators of disease in Mendelian randomization analysis.

scholarly journals Association of size at birth with adolescent hormone levels, body size and age at menarche: relevance for breast cancer risk

2008 ◽  
Vol 99 (1) ◽  
pp. 201-206 ◽  
Author(s):  
S Opdahl ◽  
T I L Nilsen ◽  
P R Romundstad ◽  
E Vanky ◽  
S M Carlsen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Size ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Age At Menarche ◽  
Hormone Levels ◽  
Size At Birth

scholarly journals Breast cancer risk and the interaction between adolescent body size and weight gain in later life: A case-control study

2016 ◽  
Vol 45 ◽  
pp. 135-144 ◽  
Author(s):  
Ines Florath ◽  
Danja Sarink ◽  
Christobel Saunders ◽  
Jane Heyworth ◽  
Lin Fritschi
Keyword(s):  
Breast Cancer ◽  
Body Size ◽  
Weight Gain ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Case Control Study ◽  
Later Life ◽  
Case Control ◽  
Control Study

scholarly journals Birth size in relation to age at menarche and adolescent body size: Implications for breast cancer risk

2003 ◽  
Vol 105 (3) ◽  
pp. 400-403 ◽  
Author(s):  
P�l R. Romundstad ◽  
Lars J. Vatten ◽  
Tom I. Lund Nilsen ◽  
Turid Lingaas Holmen ◽  
Chung-cheng Hsieh ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Size ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Age At Menarche ◽  
Birth Size

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 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 Pubertal timing and breast cancer risk in the Sister Study cohort

2020 ◽  
Vol 22 (1) ◽  
Author(s):  
Mandy Goldberg ◽  
Aimee A. D’Aloisio ◽  
Katie M. O’Brien ◽  
Shanshan Zhao ◽  
Dale P. Sandler
Keyword(s):  
Breast Cancer ◽  
Risk Factor ◽  
Family History ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Birth Cohort ◽  
Pubertal Timing ◽  
Age At Menarche ◽  
Race Ethnicity ◽  
Pubertal Tempo

Abstract Background Earlier age at menarche is an established risk factor for breast cancer. While age at menarche has been fairly stable over the past half-century, age at breast development (thelarche) has continued to decrease. Recently, earlier age at thelarche and a longer time between thelarche and menarche (pubertal tempo) were shown to be associated with increased breast cancer risk. Our objective was to examine how breast cancer risk was associated with pubertal timing and tempo in a prospective US cohort. Methods Women ages 35–74 years without a history of breast cancer, but who had a sister previously diagnosed with breast cancer, were enrolled in the Sister Study from 2003 to 2009 (N = 50,884). At enrollment, participants reported their ages at thelarche and menarche. Pubertal tempo was age at menarche minus age at thelarche. We estimated adjusted hazard ratios (HRs) and 95% confidence intervals (CIs) for each pubertal milestone and risk of breast cancer (invasive or ductal carcinoma in situ) using Cox proportional hazards regression. We examined whether associations between age at thelarche and breast cancer risk were modified by birth cohort, race/ethnicity, weight at age 10, and extent of breast cancer family history, as characterized by a Bayesian score based on first-degree family structure. Results During follow-up (mean = 9.3 years), 3295 eligible women were diagnosed with breast cancer. Early ages at thelarche (HR = 1.23, 95% CI 1.03–1.46 for < 10 vs. 12–13 years) and menarche (HR = 1.10, 95% CI 1.01–1.20 for < 12 vs. 12–13 years) were positively associated with breast cancer risk. Pubertal tempo was not associated with breast cancer risk (HR = 0.99, 95% CI 0.97–1.02 per 1-year longer tempo). When considering early thelarche (< 10 years) and early menarche (< 12 years) jointly, women with both had a 30% greater risk of breast cancer compared with women with neither risk factor (95% CI 1.07–1.57). The association between age at thelarche and breast cancer risk did not significantly vary by birth cohort, race/ethnicity, childhood weight, or Bayesian family history score. Conclusions Earlier ages at thelarche and menarche may enhance susceptibility to breast carcinogenesis. Age at thelarche is an important risk factor to consider given secular trends towards earlier development.

scholarly journals Genetic variation at CYP3A is associated with age at menarche and breast cancer risk: a case-control study

2014 ◽  
Vol 16 (3) ◽  
Author(s):  
Nichola Johnson ◽  
◽  
Frank Dudbridge ◽  
Nick Orr ◽  
Lorna Gibson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Genetic Variation ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Case Control Study ◽  
Case Control ◽  
Age At Menarche ◽  
Control Study

Body size in different periods of life and breast cancer risk in post-menopausal women

1998 ◽  
Vol 76 (1) ◽  
pp. 29-34 ◽  
Author(s):  
Cecilia Magnusson ◽  
John Baron ◽  
Ingemar Persson ◽  
Alicja Wolk ◽  
Reinhold Bergström ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Body Size ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Menopausal Women ◽  
Post Menopausal

scholarly journals Investigating causal relations between sleep traits and risk of breast cancer in women: mendelian randomisation study

BMJ ◽  
2019 ◽  
pp. l2327 ◽  
Author(s):  
Rebecca C Richmond ◽  
Emma L Anderson ◽  
Hassan S Dashti ◽  
Samuel E Jones ◽  
Jacqueline M Lane ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Protective Effect ◽  
Sleep Duration ◽  
Breast Cancer Diagnosis ◽  
Mendelian Randomisation ◽  
Uk Biobank ◽  
Multivariable Regression ◽  
Insomnia Symptoms

Abstract Objective To examine whether sleep traits have a causal effect on risk of breast cancer. Design Mendelian randomisation study. Setting UK Biobank prospective cohort study and Breast Cancer Association Consortium (BCAC) case-control genome-wide association study. Participants 156 848 women in the multivariable regression and one sample mendelian randomisation (MR) analysis in UK Biobank (7784 with a breast cancer diagnosis) and 122 977 breast cancer cases and 105 974 controls from BCAC in the two sample MR analysis. Exposures Self reported chronotype (morning or evening preference), insomnia symptoms, and sleep duration in multivariable regression, and genetic variants robustly associated with these sleep traits. Main outcome measure Breast cancer diagnosis. Results In multivariable regression analysis using UK Biobank data on breast cancer incidence, morning preference was inversely associated with breast cancer (hazard ratio 0.95, 95% confidence interval 0.93 to 0.98 per category increase), whereas there was little evidence for an association between sleep duration and insomnia symptoms. Using 341 single nucleotide polymorphisms (SNPs) associated with chronotype, 91 SNPs associated with sleep duration, and 57 SNPs associated with insomnia symptoms, one sample MR analysis in UK Biobank provided some supportive evidence for a protective effect of morning preference on breast cancer risk (0.85, 0.70, 1.03 per category increase) but imprecise estimates for sleep duration and insomnia symptoms. Two sample MR using data from BCAC supported findings for a protective effect of morning preference (inverse variance weighted odds ratio 0.88, 95% confidence interval 0.82 to 0.93 per category increase) and adverse effect of increased sleep duration (1.19, 1.02 to 1.39 per hour increase) on breast cancer risk (both oestrogen receptor positive and oestrogen receptor negative), whereas evidence for insomnia symptoms was inconsistent. Results were largely robust to sensitivity analyses accounting for horizontal pleiotropy. Conclusions Findings showed consistent evidence for a protective effect of morning preference and suggestive evidence for an adverse effect of increased sleep duration on breast cancer risk.

Sign in / Sign up

Export Citation Format

Share Document