Ageing-related markers and risks of cancer and cardiovascular disease: a prospective study in the EPIC-Heidelberg cohort

AbstractBiological age is an important risk factor for chronic diseases. We examined the associations between five markers of unhealthy ageing; Growth Differentiation Factor-15 (GDF-15), N-terminal pro-brain natriuretic peptide (NT-proBNP), glycated hemoglobin A1c (HbA1C), C-Reactive Protein (CRP) and cystatin-C; with risks of cancer and cardiovascular disease (CVD). We used a case-cohort design embedded in the EPIC-Heidelberg cohort, including a subcohort of 3792 participants along with 4867 incident cases of cancer and CVD. Hazard ratios (HRs) were computed and the strongest associations were used to build weighted multi-marker combinations, and their associations with cancer and CVD risks were tested. After adjusting for common confounders, we observed direct associations of GDF-15 with lung cancer risk, NT-proBNP with breast, prostate and colorectal cancers, HbA1C with lung, colorectal, and breast cancer risks, and CRP with lung and colorectal cancer risks. An inverse association was observed for GDF-15 and prostate cancer risk. We also found direct associations of all 5 markers with myocardial infarction (MI) risk, and of GDF-15, NT-proBNP, CRP and cystatin-C with stroke risk. A combination of the independently-associated markers showed a moderately strong association with the risks of cancer and CVD (HRQ4-Q1 ranged from 1.78[1.36, 2.34] for breast cancer, when combining NT-proBNP and HbA1C, to 2.87[2.15, 3.83] for MI when combining NT-proBNP, HbA1C, CRP and cystatin-C). This analysis suggests that combinations of biomarkers related to unhealthy ageing show strong associations with cancer risk, and corroborates published evidence on CVD risk. If confirmed in other studies, using these biomarkers could be useful for the identification of individuals at higher risk of age-related diseases.

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Anthropometric measures, plasma adiponectin, and breast cancer risk

Endocrine Related Cancer ◽

10.1677/erc-06-0089 ◽

2007 ◽

Vol 14 (3) ◽

pp. 669-677 ◽

Cited By ~ 60

Author(s):

Yu-Feng Tian ◽

Chi-Hong Chu ◽

Mei-Hsuan Wu ◽

Chia-Lin Chang ◽

Tsan Yang ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Premenopausal Women ◽

Health Examination ◽

Inverse Association ◽

Anthropometric Measures ◽

Plasma Adiponectin ◽

Er Positive ◽

Incident Cases

Adiponectin is a peptide hormone secreted exclusively by adipocytes, and obesity is an established risk factor for breast cancer. We have, thus, evaluated the associations of anthropometric measures of adiposity and adiponectin with the development of breast cancer in a case–control study. Questionnaire information, anthropometric measures, and blood samples were taken before treatment from 244 incident cases with breast cancer, including 141 premenopausal and 103 postmenopausal cases, and 244 controls admitted for health examination at the Tri-Service General Hospital, Taipei between 2004 and 2005. Plasma levels of adiponectin were measured by RIA. The relationship between anthropometric measures of adiposity and breast cancer risk was modified by menopausal status, with a significant increase in risk observed in postmenopausal but not premenopausal women. Moreover, a fairly robust inverse association of adiponectin with the risk was observed only in postmenopausal women (adjusted odds ratio (OR), 0.55; 95% confidence interval (CI), 0.23–0.97), but not in premenopausal women. Additionally, the plasma adiponectin levels tended to be inversely associated with estrogen receptor (ER)-positive (adjusted OR, 0.53; 95% CI, 0.27–0.98) but not ER-negative breast tumors. Furthermore, the associations of adiponectin with breast cancer risk overall and by menopausal and ER status remained after adjustment for obesity indices. These results suggest that adiponectin may have an independent role in breast carcinogenesis, particularly in the postmenopausal and ER-positive breast cancer risk.

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Increased adiposity is protective for breast and prostate cancer: a Mendelian randomisation study using up to 132,413 breast cancer cases and 85,907 prostate cancer cases

10.1101/2020.04.02.20049031 ◽

2020 ◽

Author(s):

H. A. Amin ◽

P. Kaewsri ◽

A. M. Yiorkas ◽

H. Cooke ◽

A. I. Blakemore ◽

...

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Cancer Risk ◽

Causal Effect ◽

Prostate Cancer Risk ◽

Mendelian Randomisation ◽

Health Campaigns ◽

Fat Percentage ◽

Published Evidence ◽

Breast And Prostate Cancer

ABSTRACTBackgroundBreast and prostate cancer are the first and second most common types of cancer in women and men, respectively. A recent campaign by Cancer Research UK emphasised obesity as being a causal risk factor for cancer, although previously published evidence is heterogenous. We aimed to explore the causal effect of adiposity on breast and prostate cancer risk in the UK Biobank (UKB), a large prospective cohort study, and published data.MethodsWe used Mendelian randomisation (MR) to assess the causal effect of body mass index (BMI), body fat percentage (BFP), waist circumference (WC), hip circumference (HC), and waist-to-hip ratio (WHR) on breast and prostate cancer risk.ResultsWe obtained estimates (odds ratios, OR, per SD unit increase) of the causal effect of the adiposity measures on breast and prostate cancer risk. BMI and HC decrease the risk of breast cancer (OR 0.776 [95% CIs 0.661-0.91] and OR 0.781 [95% CIs 0.649-0.94], respectively). WC, BFP, and BMI decrease the risk of prostate cancer (OR 0.602 [95% CIs 0.439-0.825], OR 0.629 [95% CIs 0.414-0.956], and OR 0.695 [95% CIs 0.553-0.874], respectively). The protective effect of adiposity on prostate cancer risk is enhanced in men who are exposed to potentially hazardous substances at work, and the association between BMI and breast cancer is confounded by variables associated with general health.ConclusionsIn conclusion, increasing adiposity is causally protective for breast and prostate cancer and the effects in prostate cancer may, at least partly, be due to the safe storage of chemicals in adipose cells. It is necessary to explore the mechanisms through which adiposity may protect against or be a risk factor for cancer, to identify how the latter can be minimised without sacrificing the former, and to base public health campaigns around sound evidence.HIGHLIGHTSPreviously published evidence regarding the effect of adiposity on prostate and breast cancer risk is heterogenousIncreasing BMI and hip circumference decrease the risk of breast cancer in womenIncreasing waist circumference, body fat percentage, and BMI decrease the risk of prostate cancerThe protective effect of adiposity on prostate cancer is stronger in men who are exposed to carcinogens at workPublic health campaigns need to target the negative aspects of adiposity whilst preserving the positive aspects

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

International Journal of Epidemiology ◽

10.1093/ije/dyy201 ◽

2018 ◽

Vol 48 (3) ◽

pp. 795-806 ◽

Cited By ~ 19

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.

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First-degree family history of breast cancer is associated with prostate cancer risk: a systematic review and meta-analysis

BMC Cancer ◽

10.1186/s12885-019-6055-9 ◽

2019 ◽

Vol 19 (1) ◽

Cited By ~ 2

Author(s):

Zheng-Ju Ren ◽

De-Hong Cao ◽

Qin Zhang ◽

Peng-Wei Ren ◽

Liang-Ren Liu ◽

...

Keyword(s):

Breast Cancer ◽

Prostate Cancer ◽

Systematic Review ◽

Family History ◽

Cancer Risk ◽

Meta Analysis ◽

Prostate Cancer Risk ◽

History Of

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Prediction of Breast and Prostate Cancer Risks in Male BRCA1 and BRCA2 Mutation Carriers Using Polygenic Risk Scores

Journal of Clinical Oncology ◽

10.1200/jco.2016.69.4935 ◽

2017 ◽

Vol 35 (20) ◽

pp. 2240-2250 ◽

Cited By ~ 69

Author(s):

Julie Lecarpentier ◽

Valentina Silvestri ◽

Karoline B. Kuchenbaecker ◽

Daniel Barrowdale ◽

Joe Dennis ◽

...

Keyword(s):

Prostate Cancer ◽

Cancer Risk ◽

Cancer Susceptibility ◽

Prostate Cancer Risk ◽

Risk Scores ◽

Cancer Risks ◽

Prostate Cancer Susceptibility ◽

Common Genetic Variants ◽

Breast And Prostate Cancer ◽

Male Carriers

Purpose BRCA1/2 mutations increase the risk of breast and prostate cancer in men. Common genetic variants modify cancer risks for female carriers of BRCA1/2 mutations. We investigated—for the first time to our knowledge—associations of common genetic variants with breast and prostate cancer risks for male carriers of BRCA1/ 2 mutations and implications for cancer risk prediction. Materials and Methods We genotyped 1,802 male carriers of BRCA1/2 mutations from the Consortium of Investigators of Modifiers of BRCA1/2 by using the custom Illumina OncoArray. We investigated the combined effects of established breast and prostate cancer susceptibility variants on cancer risks for male carriers of BRCA1/2 mutations by constructing weighted polygenic risk scores (PRSs) using published effect estimates as weights. Results In male carriers of BRCA1/2 mutations, PRS that was based on 88 female breast cancer susceptibility variants was associated with breast cancer risk (odds ratio per standard deviation of PRS, 1.36; 95% CI, 1.19 to 1.56; P = 8.6 × 10−6). Similarly, PRS that was based on 103 prostate cancer susceptibility variants was associated with prostate cancer risk (odds ratio per SD of PRS, 1.56; 95% CI, 1.35 to 1.81; P = 3.2 × 10−9). Large differences in absolute cancer risks were observed at the extremes of the PRS distribution. For example, prostate cancer risk by age 80 years at the 5th and 95th percentiles of the PRS varies from 7% to 26% for carriers of BRCA1 mutations and from 19% to 61% for carriers of BRCA2 mutations, respectively. Conclusion PRSs may provide informative cancer risk stratification for male carriers of BRCA1/2 mutations that might enable these men and their physicians to make informed decisions on the type and timing of breast and prostate cancer risk management.

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Binge Drinking and Risk of Breast Cancer: Results from the SUN (‘Seguimiento Universidad de Navarra’) Project

Nutrients ◽

10.3390/nu12030731 ◽

2020 ◽

Vol 12 (3) ◽

pp. 731

Author(s):

Rodrigo Sánchez-Bayona ◽

Alfredo Gea ◽

Itziar Gardeazabal ◽

Andrea Romanos-Nanclares ◽

Miguel Ángel Martínez-González ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Binge Drinking ◽

Cox Regression ◽

Menopausal Status ◽

The Sun ◽

Stratified Analysis ◽

Incident Cases

Alcohol intake is associated with the risk of breast cancer. Different patterns of alcohol-drinking may have different effects on breast cancer even when keeping constant the total amount of alcohol consumed. We aimed to assess the association between binge drinking and breast cancer risk. The SUN Project is a Spanish dynamic prospective cohort of university graduates initiated in 1999. In the 556-item lifestyle baseline questionnaire a validated food-frequency questionnaire was embedded. Participants completed biennial follow-up questionnaires. Cox regression models were used to estimate the hazard ratio (HR) for breast cancer associated with the exposure to binge drinking. A stratified analysis was performed according to menopausal status. We included 9577 women (mean age = 34 years, SD = 10 years), with a median follow-up of 11.8 years. Among 104,932 women-years of follow-up, we confirmed 88 incident cases of breast cancer. Women in the binge drinking group showed a higher risk of breast cancer (HR = 1.76; 95% CI: 1.03–2.99) compared to women in the non-binge drinking category. In the stratified analysis, a 2-fold higher risk for premenopausal breast cancer was associated with binge drinking habit (HR = 2.06; 95% CI: 1.11–3.82). This study adds new evidence on the association of binge drinking with breast cancer risk.

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Polygenic risk score for the prediction of breast cancer is related to lesser terminal duct lobular unit involution of the breast

npj Breast Cancer ◽

10.1038/s41523-020-00184-7 ◽

2020 ◽

Vol 6 (1) ◽

Author(s):

Clara Bodelon ◽

Hannah Oh ◽

Andriy Derkach ◽

Joshua N. Sampson ◽

Brian L. Sprague ◽

...

Keyword(s):

Breast Cancer ◽

Breast Cancer Risk ◽

Cancer Risk ◽

Risk Score ◽

Polygenic Risk Score ◽

Intermediate Step ◽

Breast Cancers ◽

Tissue Samples ◽

Polygenic Risk ◽

Age Related

Abstract Terminal duct lobular units (TDLUs) are the predominant anatomical structures where breast cancers originate. Having lesser degrees of age-related TDLU involution, measured as higher TDLUs counts or more epithelial TDLU substructures (acini), is related to increased breast cancer risk among women with benign breast disease (BBD). We evaluated whether a recently developed polygenic risk score (PRS) based on 313-common variants for breast cancer prediction is related to TDLU involution in the background, normal breast tissue, as this could provide mechanistic clues on the genetic predisposition to breast cancer. Among 1398 women without breast cancer, higher values of the PRS were significantly associated with higher TDLU counts (P = 0.004), but not with acini counts (P = 0.808), in histologically normal tissue samples from donors and diagnostic BBD biopsies. Mediation analysis indicated that TDLU counts may explain a modest proportion (≤10%) of the association of the 313-variant PRS with breast cancer risk. These findings suggest that TDLU involution might be an intermediate step in the association between common genetic variation and breast cancer risk.

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