| 1. |
- Barot, Shabane, et al.
(author)
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Combined associations of a healthy lifestyle and body mass index with colorectal cancer recurrence and survival : a cohort study
- 2024
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In: Cancer Causes and Control. - : Springer Nature. - 0957-5243 .- 1573-7225. ; 35:2, s. 367-376
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Journal article (peer-reviewed)abstract
- PURPOSE: Colorectal cancer (CRC) risk is associated with modifiable lifestyle factors including smoking, physical inactivity, Western diet, and excess body weight. The impact of lifestyle factors on survival is less known. A cohort study was conducted to investigate the combined effects of a healthy lifestyle and body mass index on prognosis following CRC diagnosis.METHODS: Treatment and follow-up data were collected from the patient files of 1098 participants from the Colorectal cancer low-risk study cohort including stage I-III CRC patients. A healthy lifestyle and BMI (HL) score was computed using self-reported data on smoking status, physical activity, adherence to a Mediterranean diet pattern, and BMI, and divided into four categories ranging from least to most healthy. Survival analyses were performed to assess recurrence-free survival and overall survival across categories of exposure, using the Kaplan-Meier method and Cox proportional hazards models adjusted for age, sex, and educational level.RESULTS: Among 1098 participants with stage I-III CRC, 233 (21.2%) had an HL score of 0-1 (least healthy), 354 (32.2%) HL score of 2, 357 (32.5%) HL score of 3 and 154 (14.0) HL score 4 (most healthy). Patients with the healthiest lifestyle (HL score 4) compared to the least healthy (HL score 0-1) had an improved recurrence-free survival (HL 4 vs HL 0-1, HRadj 0.51 (95% CI 0.31-0.83) and overall survival (HL 4 vs HL 0-1, HRadj 0.52 (95% CI 0.38-0.70).CONCLUSION: Adherence to a healthy lifestyle may increase the recurrence-free and overall survival of patients with stage I-III CRC.
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| 2. |
- Bjöhle, Judith, et al.
(author)
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Post-mastectomy radiation therapy with or without implant-based reconstruction is safe in terms of clinical target volume coverage and survival : A matched cohort study
- 2019
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In: Radiotherapy and Oncology. - : Elsevier BV. - 0167-8140 .- 1879-0887. ; 131, s. 229-236
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Journal article (peer-reviewed)abstract
- BACKGROUND AND PURPOSE: Patients with breast cancer receiving mastectomy in our institution are offered immediate breast reconstruction (IBR). IBR may have an impact on the optimisation of radiation therapy (RT). Therefore, we aimed to evaluate the clinical target volume (CTV) dose coverage when disregarding the dose received by the breast implant in women treated for breast cancer. Furthermore, to investigate the safety of immediate breast reconstruction (IBR) with an implant (IBR+) in terms of recurrence and survival compared to patients without an implant (IBR-).PATIENTS AND METHODS: This matched-cohort included 128 patients with IBR+ and 252 IBR- patients (controls). The potential confounding effects of tumour stage and treatment were controlled for. For IBR+ patients, the implant volume was excluded from the CTV in the RT planning images, and the RT target coverage (V95%: CTV covered by ≥the 95% isodose) was compared between the IBR+ and IBR- groups.RESULTS: A limited under dosage was observed in patients without lymph-node irradiation; the V95% mean values for the CTV subtracting the implant were 84% and 92%, for IBR+ and IBR- groups, respectively. Median follow-up duration was 5.8 years (0.1-7.5 years). In comparing IBR+ and IBR- groups, no statistically significant differences were found in the incidence of recurrence rate ratios or recurrence free survival (log-rank p = 0.142), overall survival (log-rank p = 0.096), or breast cancer specific survival (log-rank p = 0.147).CONCLUSIONS: Post-mastectomy radiation therapy and implant-based reconstruction lead to minor under dosage of the target, due to the projection of the subcutaneous tissue in the presence of the implant. However, recurrence and survival rates were equally distributed among IBR+ and IBR- patients indicating that the overall treatment protocol used in our institution is safe.
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| 3. |
- Colzani, Edoardo, et al.
(author)
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Risk of hospitalization and death due to bone fractures after breast cancer: a registry-based cohort study
- 2016
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In: British Journal of Cancer. - Stockholm : Karolinska Institutet, Dept of Medical Epidemiology and Biostatistics. - 0007-0920 .- 1532-1827.
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Journal article (peer-reviewed)abstract
- BACKGROUND: Bone fractures may have an impact on prognosis of breast cancer. The long-term risks of bone fracture in breast cancer patients have not been thoroughly studied. METHODS: Poisson regression was used to investigate the incidence of hospitalisation due to bone fracture comparing women with and without breast cancer based on Swedish National registers. Cox regression was used to investigate the risk of being hospitalised with bone fracture, and subsequent risk of death, in a regional cohort of breast cancer patients. RESULTS: For breast cancer patients, the 5-year risk of bone fracture hospitalisation was 4.8% and the 30-day risk of death following a bone fracture hospitalisation was 2.0%. Compared with the general population, breast cancer patients had incidence rate ratios of 1.25 (95% CI: 1.23-1.28) and 1.18 (95% CI: 1.14-1.22) for hospitalisation due to any bone fracture and hip fracture, respectively. These ratios remained significantly increased for 10 years. Comorbidities (Charlson Comorbidity Index 1) were associated with the risk of being hospitalised with bone fracture. Women taking aromatase inhibitors were at an increased risk as compared with women taking tamoxifen (HR=1.48; 95% CI: 0.98-2.22). Breast cancer patients hospitalised for a bone fracture showed a higher risk of death (HR=1.83; 95% CI: 1.50-2.22) compared with those without bone fracture. CONCLUSIONS: Women with a previous breast cancer diagnosis are at an increased risk of hospitalisation due to a bone fracture, particularly if they have other comorbidities.
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| 4. |
- Ding, Yuan C, et al.
(author)
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A nonsynonymous polymorphism in IRS1 modifies risk of developing breast and ovarian cancers in BRCA1 and ovarian cancer in BRCA2 mutation carriers
- 2012
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In: Cancer Epidemiology, Biomarkers and Prevention. - : American Association for Cancer Research. - 1055-9965 .- 1538-7755. ; 21:8, s. 1362-1370
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Journal article (peer-reviewed)abstract
- BACKGROUND: We previously reported significant associations between genetic variants in insulin receptor substrate 1 (IRS1) and breast cancer risk in women carrying BRCA1 mutations. The objectives of this study were to investigate whether the IRS1 variants modified ovarian cancer risk and were associated with breast cancer risk in a larger cohort of BRCA1 and BRCA2 mutation carriers.METHODS: IRS1 rs1801123, rs1330645, and rs1801278 were genotyped in samples from 36 centers in the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Data were analyzed by a retrospective cohort approach modeling the associations with breast and ovarian cancer risks simultaneously. Analyses were stratified by BRCA1 and BRCA2 status and mutation class in BRCA1 carriers.RESULTS: Rs1801278 (Gly972Arg) was associated with ovarian cancer risk for both BRCA1 (HR, 1.43; 95% confidence interval (CI), 1.06-1.92; P = 0.019) and BRCA2 mutation carriers (HR, 2.21; 95% CI, 1.39-3.52, P = 0.0008). For BRCA1 mutation carriers, the breast cancer risk was higher in carriers with class II mutations than class I mutations (class II HR, 1.86; 95% CI, 1.28-2.70; class I HR, 0.86; 95%CI, 0.69-1.09; P(difference), 0.0006). Rs13306465 was associated with ovarian cancer risk in BRCA1 class II mutation carriers (HR, 2.42; P = 0.03).CONCLUSION: The IRS1 Gly972Arg single-nucleotide polymorphism, which affects insulin-like growth factor and insulin signaling, modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers and breast cancer risk in BRCA1 class II mutation carriers.Impact: These findings may prove useful for risk prediction for breast and ovarian cancers in BRCA1 and BRCA2 mutation carriers.
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| 5. |
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| 6. |
- Hamdi, Yosr, et al.
(author)
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Association of breast cancer risk in BRCA1 and BRCA2 mutation carriers with genetic variants showing differential allelic expression : identification of a modifier of breast cancer risk at locus 11q22.3
- 2017
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In: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 161:1, s. 117-134
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Journal article (peer-reviewed)abstract
- Purpose: Cis-acting regulatory SNPs resulting in differential allelic expression (DAE) may, in part, explain the underlying phenotypic variation associated with many complex diseases. To investigate whether common variants associated with DAE were involved in breast cancer susceptibility among BRCA1 and BRCA2 mutation carriers, a list of 175 genes was developed based of their involvement in cancer-related pathways. Methods: Using data from a genome-wide map of SNPs associated with allelic expression, we assessed the association of ~320 SNPs located in the vicinity of these genes with breast and ovarian cancer risks in 15,252 BRCA1 and 8211 BRCA2 mutation carriers ascertained from 54 studies participating in the Consortium of Investigators of Modifiers of BRCA1/2. Results: We identified a region on 11q22.3 that is significantly associated with breast cancer risk in BRCA1 mutation carriers (most significant SNP rs228595 p = 7 × 10−6). This association was absent in BRCA2 carriers (p = 0.57). The 11q22.3 region notably encompasses genes such as ACAT1, NPAT, and ATM. Expression quantitative trait loci associations were observed in both normal breast and tumors across this region, namely for ACAT1, ATM, and other genes. In silico analysis revealed some overlap between top risk-associated SNPs and relevant biological features in mammary cell data, which suggests potential functional significance. Conclusion: We identified 11q22.3 as a new modifier locus in BRCA1 carriers. Replication in larger studies using estrogen receptor (ER)-negative or triple-negative (i.e., ER-, progesterone receptor-, and HER2-negative) cases could therefore be helpful to confirm the association of this locus with breast cancer risk.
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| 7. |
- Liljegren, Annelie
(author)
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Hereditary colorectal cancer : predisposition and prevention
- 2004
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Doctoral thesis (other academic/artistic)abstract
- This thesis focuses on the clinical results from a ten-year long follow-up surveillance program, including regular colonoscopy, for subjects (n=304, 780 colonoscopies) with increased risk of colorectal cancer, and on psychological aspects of the program. The cohort included persons with hereditary nonpolyposis colorectal cancer (HNPCC) and persons assumed to be at increased risk of colorectal cancer because they had two (Two close relatives, TCR) or three or more relatives (Hereditary colorectal cancer, HCRC) afflicted with colorectal cancer. In addition, an international cohort of subjects with HNPCC (n=532) was evaluated regarding the prevalence of adenomas and hyperplastic polyps. In paper I we found a significantly increased risk of developing an adenoma before the age of 54 years in all risk groups as compared with a reference population (three autopsy studies). We found no significant differences with respect to prevalence of adenomas between the three family types or between sexes. However, the age of onset of the adenomas was earlier and the grade of dysplasia was higher in adenomas in HNPCC than in the other groups, HCRC and TCR. In paper II we found a significant positive correlation between the numbers of hyperplastic polyps and adenomas in the whole study population and a similar correlation was seen in all three family types as well as during follow-up. Predictors for the detection of adenomas and hyperplastic polyps were increasing age and observation time. A positive finding of either a hyperplastic polyp or an adenoma at first colonoscopy was a predictor for future findings of both types of colon polyps. In paper III we found that the average perceived benefit of regular colonoscopies rated 8.0 on the visual analogue scale (VAS range 1-10). There was a wide range of risk perception and 61% of the mutation carriers reported their personal risk as being 40% or less. Increasing age and a longer surveillance (increased number of colonoscopies) were significantly and positively associated with less discomfort. All HAD anxiety and depression values were within the normative data range. The measurement of quality of life (SF-36) showed significantly lower values regarding mental health among males, and vitality among females as compared with the general population. In paper IV we found that the prevalence of adenomas and hyperplastic polyps among HNPCC individuals was 18% and 10%, respectively. A significant positive correlation was found between the adenomas and hyperplastic polyps in the whole study population. In summary, individuals with increased risk of colorectal cancer due to hereditary factors run a greater risk of developing adenomas than the general population. The majority of the population at risk tolerates regular colonoscopies well. The correlation between adenomas and hyperplastic polyps found in this population indicates that hyperplastic polyps may act as a marker for mutation carriers and should be taken into consideration when screening programs are designed.
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| 8. |
- Spurdle, Amanda B., et al.
(author)
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Common Genetic Variation at BARD1 Is Not Associated with Breast Cancer Risk in BRCA1 or BRCA2 Mutation Carriers
- 2011
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In: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755 .- 1055-9965. ; 20:5, s. 1032-1038
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Journal article (peer-reviewed)abstract
- Background: Inherited BRCA1 and BRCA2 (BRCA1/2) mutations confer elevated breast cancer risk. Knowledge of factors that can improve breast cancer risk assessment in BRCA1/2 mutation carriers may improve personalized cancer prevention strategies. Methods: A cohort of 5,546 BRCA1 and 2,865 BRCA2 mutation carriers was used to evaluate risk of breast cancer associated with BARD1 Cys557Ser. In a second nonindependent cohort of 1,537 of BRCA1 and 839 BRCA2 mutation carriers, BARD1 haplotypes were also evaluated. Results: The BARD1 Cys557Ser variant was not significantly associated with risk of breast cancer from single SNP analysis, with a pooled effect estimate of 0.90 (95% CI: 0.71-1.15) in BRCA1 carriers and 0.87 (95% CI: 0.59-1.29) in BRCA2 carriers. Further analysis of haplotypes at BARD1 also revealed no evidence that additional common genetic variation not captured by Cys557Ser was associated with breast cancer risk. Conclusion: Evidence to date does not support a role for BARD1 variation, including the Cy557Ser variant, as a modifier of risk in BRCA1/2 mutation carriers. Impact: Interactors of BRCA1/2 have been implicated as modifiers of BRCA1/2-associated cancer risk. Our finding that BARD1 does not contribute to this risk modification may focus research on other genes that do modify BRCA1/2-associated cancer risk. Cancer Epidemiol Biomarkers Prev; 20(5); 1032-38. (C) 2011 AACR.
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| 9. |
- Vigorito, Elena, et al.
(author)
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Fine-Scale Mapping at 9p22.2 Identifies Candidate Causal Variants That Modify Ovarian Cancer Risk in BRCA1 and BRCA2 Mutation Carriers
- 2016
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In: PLOS ONE. - : Public Library of Science (PLoS). - 1932-6203. ; 11:7
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Journal article (peer-reviewed)abstract
- Population-based genome wide association studies have identified a locus at 9p22.2 associated with ovarian cancer risk, which also modifies ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. We conducted fine-scale mapping at 9p22.2 to identify potential causal variants in BRCA1 and BRCA2 mutation carriers. Genotype data were available for 15,252 (2,462 ovarian cancer cases) BRCA1 and 8,211 (631 ovarian cancer cases) BRCA2 mutation carriers. Following genotype imputation, ovarian cancer associations were assessed for 4,873 and 5,020 SNPs in BRCA1 and BRCA2 mutation carriers respectively, within a retrospective cohort analytical framework. In BRCA1 mutation carriers one set of eight correlated candidate causal variants for ovarian cancer risk modification was identified (top SNP rs10124837, HR: 0.73, 95% CI: 0.68 to 0.79, p-value 2x 10-16). These variants were located up to 20 kb upstream of BNC2. In BRCA2 mutation carriers one region, up to 45 kb upstream of BNC2, and containing 100 correlated SNPs was identified as candidate causal (top SNP rs62543585, HR: 0.69, 95% CI: 0.59 to 0.80, p-value 1.0 x 10-6). The candidate causal in BRCA1 mutation carriers did not include the strongest associated variant at this locus in the general population. In sum, we identified a set of candidate causal variants in a region that encompasses the BNC2 transcription start site. The ovarian cancer association at 9p22.2 may be mediated by different variants in BRCA1 mutation carriers and in the general population. Thus, potentially different mechanisms may underlie ovarian cancer risk for mutation carriers and the general population.
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| 10. |
- Walker, Logan C, et al.
(author)
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Evidence for SMAD3 as a modifier of breast cancer risk in BRCA2 mutation carriers.
- 2010
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In: Breast cancer research : BCR. - : Springer Science and Business Media LLC. - 1465-542X .- 1465-5411. ; 12:6
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Journal article (peer-reviewed)abstract
- Current attempts to identify genetic modifiers of BRCA1 and BRCA2 associated risk have focused on a candidate gene approach, based on knowledge of gene functions, or the development of large genome-wide association studies. In this study, we evaluated 24 SNPs tagged to 14 candidate genes derived through a novel approach that analysed gene expression differences to prioritise candidate modifier genes for association studies.
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