| 1. |
- Escala-Garcia, Maria, et al.
(författare)
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A network analysis to identify mediators of germline-driven differences in breast cancer prognosis
- 2020
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Ingår i: Nature Communications. - : NATURE PUBLISHING GROUP. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- Identifying the underlying genetic drivers of the heritability of breast cancer prognosis remains elusive. We adapt a network-based approach to handle underpowered complex datasets to provide new insights into the potential function of germline variants in breast cancer prognosis. This network-based analysis studies similar to 7.3 million variants in 84,457 breast cancer patients in relation to breast cancer survival and confirms the results on 12,381 independent patients. Aggregating the prognostic effects of genetic variants across multiple genes, we identify four gene modules associated with survival in estrogen receptor (ER)-negative and one in ER-positive disease. The modules show biological enrichment for cancer-related processes such as G-alpha signaling, circadian clock, angiogenesis, and Rho-GTPases in apoptosis.
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| 2. |
- Kapoor, Pooja Middha, et al.
(författare)
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Combined associations of a polygenic risk score and classical risk factors with breast cancer risk
- 2021
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Ingår i: Journal of the National Cancer Institute. - : Oxford University Press (OUP). - 0027-8874 .- 1460-2105. ; 113:3, s. 329-337
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Tidskriftsartikel (refereegranskat)abstract
- We evaluated the joint associations between a new 313-variant PRS (PRS313) and questionnaire-based breast cancer risk factors for women of European ancestry, using 72 284 cases and 80 354 controls from the Breast Cancer Association Consortium. Interactions were evaluated using standard logistic regression and a newly developed case-only method for breast cancer risk overall and by estrogen receptor status. After accounting for multiple testing, we did not find evidence that per-standard deviation PRS313 odds ratio differed across strata defined by individual risk factors. Goodness-of-fit tests did not reject the assumption of a multiplicative model between PRS313 and each risk factor. Variation in projected absolute lifetime risk of breast cancer associated with classical risk factors was greater for women with higher genetic risk (PRS313 and family history) and, on average, 17.5% higher in the highest vs lowest deciles of genetic risk. These findings have implications for risk prevention for women at increased risk of breast cancer.
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| 3. |
- Schoemaker, Minouk J., et al.
(författare)
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Adult weight change and premenopausal breast cancer risk : A prospective pooled analysis of data from 628,463 women
- 2020
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 147:5, s. 1306-1314
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Tidskriftsartikel (refereegranskat)abstract
- Early-adulthood body size is strongly inversely associated with risk of premenopausal breast cancer. It is unclear whether subsequent changes in weight affect risk. We pooled individual-level data from 17 prospective studies to investigate the association of weight change with premenopausal breast cancer risk, considering strata of initial weight, timing of weight change, other breast cancer risk factors and breast cancer subtype. Hazard ratios (HR) and 95% confidence intervals (CI) were obtained using Cox regression. Among 628,463 women, 10,886 were diagnosed with breast cancer before menopause. Models adjusted for initial weight at ages 18-24 years and other breast cancer risk factors showed that weight gain from ages 18-24 to 35-44 or to 45-54 years was inversely associated with breast cancer overall (e.g., HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.95-0.98) and with oestrogen-receptor(ER)-positive breast cancer (HR per 5 kg to ages 45-54: 0.96, 95% CI: 0.94-0.98). Weight gain from ages 25-34 was inversely associated with ER-positive breast cancer only and weight gain from ages 35-44 was not associated with risk. None of these weight gains were associated with ER-negative breast cancer. Weight loss was not consistently associated with overall or ER-specific risk after adjusting for initial weight. Weight increase from early-adulthood to ages 45-54 years is associated with a reduced premenopausal breast cancer risk independently of early-adulthood weight. Biological explanations are needed to account for these two separate factors.
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| 4. |
- Lu, Donghao, et al.
(författare)
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A shared genetic contribution to breast cancer and schizophrenia.
- 2020
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- An association between schizophrenia and subsequent breast cancer has been suggested; however the risk of schizophrenia following a breast cancer is unknown. Moreover, the driving forces of the link are largely unclear. Here, we report the phenotypic and genetic positive associations of schizophrenia with breast cancer and vice versa, based on a Swedish population-based cohort and GWAS data from international consortia. We observe a genetic correlation of 0.14 (95% CI 0.09-0.19) and identify a shared locus at 19p13 (GATAD2A) associated with risks of breast cancer and schizophrenia. The epidemiological bidirectional association between breast cancer and schizophrenia may partly be explained by the genetic overlap between the two phenotypes and, hence, shared biological mechanisms.
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| 5. |
- Wang, Chengshi, et al.
(författare)
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Cardiovascular mortality among cancer survivors who developed breast cancer as a second primary malignancy
- 2020
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Ingår i: Cancer Research. - : American Association for Cancer Research. - 0008-5472 .- 1538-7445. ; 80:16
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Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Background: Patients with breast cancer are at increased risk of cardiovascular diseases and cardiovascular mortality, potentially due to treatment-related cardiotoxicity, early menopause, and psychological distress. Cancer survivors who developed breast cancer as a second malignancy (BCa-2) are common and may experience cancer treatment and distress for a second time. It is however unknown whether BCa-2 patients have increased risk of cardiovascular mortality compared to patients with breast cancer as the first malignancy (BCa-1) and the cancer-free female population.Methods: Using the Surveillance, Epidemiology, and End Results database, we conducted a cohort study including 1,024,047 patients with BCa-1 and 41,744 with BCa-2 diagnosed at age of 30 years and older during 1975-2016, and the corresponding female population of 994,415,911 person-years in the U.S.. Compared with patients with BCa-1 and the general population, we calculated incidence rate ratios (IRRs) of cardiovascular deaths among patients with BCa-2 by using multivariable Poisson regression.Results: During the median follow-up of 5.9 years (interquartile range, 2.4-11.3 years), 3,550 and 71,298 cardiovascular deaths were observed in BCa-2 and BCa-1 patients. Overall, BCa-2 patients had a mildly increased risk of cardiovascular mortality compared with the general population (IRR 1.07, 95% CI 1.03-1.10) and BCa-1 patients (IRR 1.13, 95% CI 1.10-1.17) with the adjustment of demographic factors. When comparing BCa-2 with BCa-1, the association was further independent of tumor characteristics and treatment modes (IRR 1.15, 95% CI 1.11-1.19). The elevated risk of cardiovascular mortality was mostly pronounced at age of follow-up between 30 and 79 years (IRR 1.31, 95% CI 1.23-1.40 compared with the general population; IRR 1.34, 95% CI 1.25-1.43 compared with BCa-1), whereas the risk was mildly increased, if any, at age of 80+ years compared with BCa-1 (IRR 1.07, 95% CI 1.02-1.11). The increased risk at age of 30-79 years in BCa-2 was particularly greater within the first month after cancer diagnosis compared with the general population (IRR 3.20, 95% CI 2.34-4.38). In contrast, cardiovascular mortality rate in BCa-2 was comparable to that in BCa-1 within the first month (IRR 0.87, 95% CI 0.63-1.21).Conclusions: Our findings suggest that patients with BCa-2, particularly in patients younger than 80 years, are at increased risk of cardiovascular mortality, compared with the general population and patients with BCa-1.
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| 6. |
- Wang, Chengshi, et al.
(författare)
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Cardiovascular mortality among cancer survivors who developed breast cancer as a second primary malignancy
- 2021
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Ingår i: British Journal of Cancer. - : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 125:10, s. 1450-1458
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: To assess the risk of cardiovascular mortality among cancer survivors who developed breast cancer as a second malignancy (BCa-2) compared with patients with first primary breast cancer (BCa-1) and the general population.METHODS: Using the Surveillance, Epidemiology, and End Results database, we conducted a population-based cohort study including 1,024,047 BCa-1 and 41,744 BCa-2 patients diagnosed from the age 30 between 1975 and 2016, and the corresponding US female population (994,415,911 person-years; 5,403,551 cardiovascular deaths). Compared with the general population and BCa-1 patients, we calculated incidence rate ratios (IRRs) of cardiovascular deaths among BCa-2 patients using Poisson regression. To adjust for unmeasured confounders, we performed a nested, case-crossover analysis among BCa-2 patients who died from cardiovascular disease.RESULTS: Although BCa-2 patients had a mildly increased risk of cardiovascular mortality compared with the population (IRR 1.08) and BCa-1 patients (IRR 1.15), the association was pronounced among individuals aged 30-49 years (BCa-2 vs. population: IRR 6.61; BCa-2 vs. BCa-1: IRR 3.03). The risk elevation was greatest within the first month after diagnosis, compared with the population, but comparable with BCa-1 patients. The case-crossover analysis confirmed these results.CONCLUSION: Our findings suggest that patients with BCa-2 are at increased risk of cardiovascular mortality.
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| 7. |
- Xie, Yuxin, et al.
(författare)
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Public health insurance and cancer-specific mortality risk among patients with breast cancer : A prospective cohort study in China
- 2021
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Ingår i: International Journal of Cancer. - : John Wiley & Sons. - 0020-7136 .- 1097-0215. ; 148:1, s. 28-37
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Tidskriftsartikel (refereegranskat)abstract
- Little is known about how health insurance policies, particularly in developing countries, influence breast cancer prognosis. Here, we examined the association between individual health insurance and breast cancer-specific mortality in China. We included 7436 women diagnosed with invasive breast cancer between 2009 and 2016, at West China Hospital, Sichuan University. The health insurance plan of patient was classified as either urban or rural schemes and was also categorized as reimbursement rate (ie, the covered/total charge) below or above the median. Breast cancer-specific mortality was the primary outcome. Using Cox proportional hazards models, we calculated hazard ratios (HRs) for cancer-specific mortality, contrasting rates among patients with a rural insurance scheme or low reimbursement rate to that of those with an urban insurance scheme or high reimbursement rate, respectively. During a median follow-up of 3.1 years, we identified 326 deaths due to breast cancer. Compared to patients covered by urban insurance schemes, patients covered by rural insurance schemes had a 29% increased cancer-specific mortality (95% CI 0%-65%) after adjusting for demographics, tumor characteristics and treatment modes. Reimbursement rate below the median was associated with a 42% increased rate of cancer-specific mortality (95% CI 11%-82%). Every 10% increase in the reimbursement rate is associated with a 7% (95% CI 2%-12%) reduction in cancer-specific mortality risk, particularly in patients covered by rural insurance schemes (26%, 95% CI 9%-39%). Our findings suggest that underinsured patients face a higher risk of breast cancer-specific mortality in developing countries.
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