| 1. |
- Ugalde-Morales, Emilio, et al.
(författare)
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Common shared genetic variation behind decreased risk of breast cancer in celiac disease
- 2017
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Ingår i: Scientific Reports. - : Nature Publishing Group. - 2045-2322. ; 7
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Tidskriftsartikel (refereegranskat)abstract
- There is epidemiologic evidence showing that women with celiac disease have reduced risk of later developing breast cancer, however, the etiology of this association is unclear. Here, we assess the extent of genetic overlap between the two diseases. Through analyses of summary statistics on densely genotyped immunogenic regions, we show a significant genetic correlation (r = -0.17, s.e. 0.05, P < 0.001) and overlap (Ppermuted < 0.001) between celiac disease and breast cancer. Using individuallevel genotype data from a Swedish cohort, we find higher genetic susceptibility to celiac disease summarized by polygenic risk scores to be associated with lower breast cancer risk (ORper-SD, 0.94, 95% CI 0.91 to 0.98). Common single nucleotide polymorphisms between the two diseases, with low P-values (P-CD < 1.00E-05, P-BC <= 0.05), mapped onto genes enriched for immunoregulatory and apoptotic processes. Our results suggest that the link between breast cancer and celiac disease is due to a shared polygenic variation of immune related regions, uncovering pathways which might be important for their development.
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| 2. |
- Yang, Haomin
(författare)
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Panorama of diseases associated with breast cancer
- 2018
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer is the most common cancer in women. Although the incidence of breast cancer has increased over time, so too has patient survival. Given these trends, the prevalence of breast cancer has steadily increased in recent decades, exposing these women to other associated diseases which can influence carcinogenesis, prognosis, and treatment. This thesis uses Swedish register data, combined with data from the Libro-1 and Karolinska Mammography Project for Risk Prediction of Breast Cancer (KARMA) cohorts, to study other diseases associated with breast cancer in women. Specifically, this thesis investigates how diseases in early adulthood influence the risk of breast cancer, and how overall health is affected by breast cancer treatment. In Study I, the risk of breast cancer in women with and without preeclampsia was studied using data from the Swedish Medical Birth Register and KARMA cohort. Women diagnosed with preeclampsia had a decreased risk of breast cancer and lower mammographic density. In addition, sisters of breast cancer patients and women with a high genetic predisposition to breast cancer had a lower risk of preeclampsia. This suggests that inherited factors may contribute to the inverse association between preeclampsia and breast cancer. In Study II and Study III, the risk of mental disorders and psoriasis were compared between a Swedish nationwide cohort of breast cancer patients and the general population. Women with invasive breast cancer had an increased risk of depression, anxiety, stress-related disorders, and psoriasis. This increased risk was greatest shortly after cancer diagnosis and remained over the subsequent five years. Patients with in-situ breast cancer only experienced an increased risk of stress-related disorders during the first six months after cancer diagnosis. With regard to risk predictors, the Libro-1 cohort of Stockholm-Gotland breast cancer patients showed that younger age at diagnosis, higher tumor grade, lymph node positive tumors, comorbidity, and chemotherapy were independently associated with an increased risk of depression and anxiety. The effect of tumor grade and chemotherapy was mainly limited to the first two years after diagnosis, while comorbidity contributed to long term risk. Younger age at diagnosis was the only risk factor identified for stress-related disorders; while for psoriasis, radiotherapy and mastectomy were associated with increased disease risk. Aside from these treatment-specific predictors, genetic predisposition, obesity and smoking were also risk factors for psoriasis in breast cancer patients. Study IV used a matched cohort design to describe a wide spectrum of diseases after breast cancer diagnosis. In a Swedish nationwide breast cancer cohort, breast cancer patients had an increased risk of infection and several non-communicable diseases, compared to matched healthy individuals. Diseases with the highest hazard ratios - lymphedema, radiodermatitis, and neutropenia - correspond to the side effects of surgery, radiotherapy, and chemotherapy. Despite an increased incidence of many diseases, increased mortality risk among breast cancer patients was only due to other solid cancers. A higher risk of other solid cancers could be predicted by menopausal disorders, indicating the need for gynecological surveillance of breast cancer patients. In conclusion, our results suggest that inherited factors contribute to an inverse association between preeclampsia and breast cancer, given that the inverse association was also found between preeclampsia and women with a high genetic predisposition to breast cancer. This thesis identifies an increased risk of several diseases after breast cancer diagnosis, including menopausal disorders, mental disorders, and psoriasis. Such diseases are related to cancer treatment, and suggest that a multidisciplinary perspective on post-cancer care is required for breast cancer patients.
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| 3. |
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| 4. |
- Yang, Haomin, et al.
(författare)
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Risk and predictors of psoriasis in patients with breast cancer : a Swedish population-based cohort study
- 2017
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Ingår i: BMC Medicine. - : BioMed Central. - 1741-7015. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: The risk of psoriasis in patients with breast cancer is largely unknown, as available evidence is limited to case findings. We systematically examined the incidence and risk factors of psoriasis in patients with breast cancer.METHODS: A Swedish nationwide cohort of 56,235 breast cancer patients (2001-2012) was compared to 280,854 matched reference individuals from the general population to estimate the incidence and hazard ratio (HR) of new-onset psoriasis. We also calculated HRs for psoriasis according to treatment, genetic, and lifestyle factors in a regional cohort of 8987 patients.RESULTS: In the nationwide cohort, 599 patients with breast cancer were diagnosed with psoriasis during a median follow-up of 5.1 years compared to 2795 cases in the matched reference individuals. This corresponded to an incidence rate of 1.9/1000 person-years in breast cancer patients vs. 1.7/1000 person-years in matched reference individuals. Breast cancer patients were at an increased risk of psoriasis (HR = 1.17; 95% confidence interval (CI) = 1.07-1.28), especially its most common subtype (psoriasis vulgaris; HR = 1.33; 95% CI = 1.17-1.52). The risk of psoriasis vulgaris was highest shortly after diagnosis but remained increased up to 12 years. Treatment-specific analyses indicated a higher risk of psoriasis in patients treated with radiotherapy (HR = 2.44; 95% CI = 1.44-4.12) and mastectomy (HR = 1.54, 95% CI = 1.03-2.31). Apart from treatment-specific effects, we identified genetic predisposition, obesity, and smoking as independent risk factors for psoriasis in breast cancer patients.CONCLUSIONS: The incidence of psoriasis is slightly elevated among patients with breast cancer, with treatment, lifestyle, and genetic factors defining the individual risk profile.
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| 5. |
- Yang, Haomin, et al.
(författare)
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Risk of heart disease following treatment for breast cancer - results from a population-based cohort study
- 2022
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Ingår i: eLIFE. - : eLife Sciences Publications Ltd. - 2050-084X. ; 11
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Tidskriftsartikel (refereegranskat)abstract
- Background: There is a rising concern about treatment-associated cardiotoxicities in breast cancer patients. This study aimed to determine the time- and treatment-specific incidence of arrhythmia, heart failure, and ischemic heart disease in women diagnosed with breast cancer.Methods: A register-based matched cohort study was conducted including 8015 breast cancer patients diagnosed from 2001 to 2008 in the Stockholm-Gotland region and followed up until 2017. Time-dependent risks of arrhythmia, heart failure, and ischemic heart disease in breast cancer patients were assessed using flexible parametric models as compared to matched controls from general population. Treatment-specific effects were estimated in breast cancer patients using Cox model.Results: Time-dependent analyses revealed long-term increased risks of arrhythmia and heart failure following breast cancer diagnosis. Hazard ratios (HRs) within the first year of diagnosis were 2.14 (95% CI = 1.63-2.81) for arrhythmia and 2.71 (95% CI = 1.70-4.33) for heart failure. HR more than 10 years following diagnosis was 1.42 (95% CI = 1.21-1.67) for arrhythmia and 1.28 (95% CI = 1.03-1.59) for heart failure. The risk for ischemic heart disease was significantly increased only during the first year after diagnosis (HR = 1.45, 95% CI = 1.03-2.04). Trastuzumab and anthracyclines were associated with increased risk of heart failure. Aromatase inhibitors, but not tamoxifen, were associated with risk of ischemic heart disease. No increased risk of heart disease was identified following locoregional radiotherapy.Conclusions: Administration of systemic adjuvant therapies appears to be associated with increased risks of heart disease. The risk estimates observed in this study may aid adjuvant therapy decision-making and patient counseling in oncology practices.
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| 6. |
- Yang, Haomin, et al.
(författare)
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Time-dependent risk of depression, anxiety, and stress-related disorders in patients with invasive and in situ breast cancer
- 2017
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Ingår i: International Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0020-7136 .- 1097-0215.
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Tidskriftsartikel (refereegranskat)abstract
- Despite concerns about the mental health of breast cancer patients, little is known regarding the temporal risk pattern and risk factors of common mental disorders among these patients. We estimated standardized incidence ratios (SIRs) of depression, anxiety and stress-related disorders in a Swedish nationwide cohort of 40,849 women with invasive and 4,402 women with in-situ breast cancer (2001- 2010, median follow-up = 4.5 years). The impact of patient, tumor and treatment characteristics was analyzed using flexible parametric survival models in a regional cohort of 7,940 invasive breast cancer patients (2001-2013, median follow-up = 7.5 years). Women with invasive breast cancer showed increased rates of depression, anxiety and stress-related disorders [overall SIR (95% CI) = 1.57 (1.46- 1.69), 1.55 (1.43-1.68) and 1.77 (1.60-1.95), respectively]. SIRs were highest shortly after diagnosis, but remained increased up to 5 years. Younger age at diagnosis, comorbidity, higher-grade disease, lymph node involvement and chemotherapy were independently associated with the risk of depression and anxiety in invasive cancer patients, with chemotherapy and higher-grade disease conferring short-term risk only, while comorbidities were mainly associated with late-onset events. No clinical risk factors were identified for stress-related disorders except for a greater risk associated with younger age. Patients with in-situ cancer only showed an increased incidence of stress-related disorders during the first six months after diagnosis [SIR (95% CI) = 2.76 (1.31-5.79)]. The time-dependent risk profile of invasive cancer patients may guide health care professionals for timely and targeted psycho-oncologic interventions.
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