| 11. |
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| 12. |
- Wang, Xiaoliang, et al.
(författare)
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Genome-wide interaction analysis of menopausal hormone therapy use and breast cancer risk among 62,370 women
- 2022
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Ingår i: Scientific Reports. - : Springer Nature. - 2045-2322. ; 12:1
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Tidskriftsartikel (refereegranskat)abstract
- Use of menopausal hormone therapy (MHT) is associated with increased risk for breast cancer. However, the relevant mechanisms and its interaction with genetic variants are not fully understood. We conducted a genome-wide interaction analysis between MHT use and genetic variants for breast cancer risk in 27,585 cases and 34,785 controls from 26 observational studies. All women were post-menopausal and of European ancestry. Multivariable logistic regression models were used to test for multiplicative interactions between genetic variants and current MHT use. We considered interaction p-values < 5 x 10(-8) as genome-wide significant, and p-values < 1 x 10(-5) as suggestive. Linkage disequilibrium (LD)-based clumping was performed to identify independent candidate variants. None of the 9.7 million genetic variants tested for interactions with MHT use reached genome-wide significance. Only 213 variants, representing 18 independent loci, had p-values < 1 x 10(5). The strongest evidence was found for rs4674019 (p-value = 2.27 x 10(-7)), which showed genome-wide significant interaction (p-value = 3.8 x 10(-8)) with current MHT use when analysis was restricted to population-based studies only. Limiting the analyses to combined estrogen-progesterone MHT use only or to estrogen receptor (ER) positive cases did not identify any genome-wide significant evidence of interactions. In this large genome-wide SNP-MHT interaction study of breast cancer, we found no strong support for common genetic variants modifying the effect of MHT on breast cancer risk. These results suggest that common genetic variation has limited impact on the observed MHT-breast cancer risk association.
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| 13. |
- Ahearn, Thomas U., et al.
(författare)
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Common variants in breast cancer risk loci predispose to distinct tumor subtypes
- 2022
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Ingår i: Breast Cancer Research. - : Springer Nature. - 1465-5411 .- 1465-542X. ; 24:1
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Tidskriftsartikel (refereegranskat)abstract
- BackgroundGenome-wide association studies (GWAS) have identified multiple common breast cancer susceptibility variants. Many of these variants have differential associations by estrogen receptor (ER) status, but how these variants relate with other tumor features and intrinsic molecular subtypes is unclear.MethodsAmong 106,571 invasive breast cancer cases and 95,762 controls of European ancestry with data on 173 breast cancer variants identified in previous GWAS, we used novel two-stage polytomous logistic regression models to evaluate variants in relation to multiple tumor features (ER, progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2) and grade) adjusting for each other, and to intrinsic-like subtypes.ResultsEighty-five of 173 variants were associated with at least one tumor feature (false discovery rate < 5%), most commonly ER and grade, followed by PR and HER2. Models for intrinsic-like subtypes found nearly all of these variants (83 of 85) associated at p < 0.05 with risk for at least one luminal-like subtype, and approximately half (41 of 85) of the variants were associated with risk of at least one non-luminal subtype, including 32 variants associated with triple-negative (TN) disease. Ten variants were associated with risk of all subtypes in different magnitude. Five variants were associated with risk of luminal A-like and TN subtypes in opposite directions.ConclusionThis report demonstrates a high level of complexity in the etiology heterogeneity of breast cancer susceptibility variants and can inform investigations of subtype-specific risk prediction.
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| 14. |
- Augustinsson, Annelie, et al.
(författare)
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Accuracy of self-reported family history of cancer, mutation status and tumor characteristics in patients with early onset breast cancer
- 2018
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Ingår i: Acta Oncologica. - 0284-186X. ; 57:5, s. 595-603
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Tidskriftsartikel (refereegranskat)abstract
- Background: The main objectives of this study were to evaluate the concordance between self-reported and registry-reported information regarding family history of breast cancer (BC), ovarian cancer (OvC) and other types of cancer in first-degree relatives of patients with early onset BC, and to determine the frequency of mutation carriers and non-mutation carriers. The secondary objective was to describe tumor characteristics for each mutation group. Material and methods: Between 1993 and 2013, 231 women who were ≤35 years old when diagnosed with BC were registered at the Oncogenetic Clinic at Skåne University Hospital in Lund, Sweden. Self-reported and registry-reported information regarding first-degree family history of cancer was collected together with information regarding tumor characteristics. Results: Almost perfect agreement was observed between self-reported and registry-reported information regarding first-degree family history of BC (κ = 0.92) and OvC (κ = 0.86). Lesser agreement was observed between reports regarding family history of other types of cancer (κ = 0.51). Mutation screening revealed pathogenic germline mutations in 30.4%; 18.8% in BRCA1, 7.1% in BRCA2 and 4.5% in other genes. Compared with other mutation groups, BRCA1 mutation carriers were more likely to be diagnosed with high-grade, ER-, PR- and triple-negative tumors. Conclusions: Our results demonstrate that physicians and genetic counselors can rely on self-reported information regarding BC and OvC in first-degree relatives. However, self-reported information regarding other types of cancer is not communicated as effectively, and there should be more focus on retrieving the correct information regarding family history of all tumor types. Furthermore, we observed that even though all BC patients fulfilled the criteria for genetic counseling and testing, a large number of patients diagnosed at ≤35 years of age did not receive genetic counseling at the Oncogenetic Clinic. This finding merits further elucidation.
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| 15. |
- Augustinsson, Annelie
(författare)
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Breast cancer in young women. Aspects of heredity and contralateral disease.
- 2021
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Breast cancer is the most commonly diagnosed cancer among women in Sweden, as well as worldwide. In Sweden, 8,288 women were diagnosed with invasive breast cancer in 2019, out of whom approximately 1.5% were younger than 35 years of age. Although breast cancer is relatively uncommon in young women, they tend to be diagnosed with more aggressive tumors at a more advanced stage, and have a poorer prognosis compared with older women. Young patients are also more likely to harbor a strong genetic predisposition for breast cancer.In paper I–III, women who were diagnosed with breast cancer at an age of 35 years or younger in the South Swedish Health Care Region were studied. In paper I, the concordance between self- and register-reported information regarding first-degree family history of cancer was evaluated. Almost perfect agreement between reports of family history of breast and ovarian cancers, but lesser agreement for other types of cancer, was observed. In addition, the frequencies of carriers and noncarriers of pathogenic variants and tumor characteristics for each of these group were described. Pathogenic variants were identified in BRCA1 (19%), BRCA2 (7%), and other genes, i.e., TP53, CHEK2, and PALB2 (4.5%). Compared with other groups, women with pathogenic variants in BRCA1 were more likely to be diagnosed with high grade, estrogen receptor-, progesterone receptor-, and triple-negative tumors. We also noted that even though all included women fulfilled the criteria for consideration of genetic counseling and testing, many had not been referred to the Oncogenetic Clinic in Lund. In paper II, we subsequently observed that both place of residence at breast cancer diagnosis and treating hospital were associated with the probability for a referral for genetic counseling and testing, and in paper III, most women stated that the main reason for not undergoing genetic testing when they were first diagnosed with breast cancer was that they had not received any information about genetic counseling and testing from their treating physicians.Among women who have previously been diagnosed with breast cancer, both young age and the identification of a pathogenic variant are associated with an increased risk for the development of a new primary breast cancer. The second breast cancer can occur ipsilaterally, i.e., in the same breast, but most occur in the contralateral breast. In paper IV, we evaluated how the incidence of contralateral breast cancer (CBC) has evolved in Sweden since the 1960s. A statistically significant increase in CBC incidence, within ten years from the first breast cancer diagnosis between the 1960s and 1980s, was observed. This increase was seen throughout all age groups, with the steepest increase in women younger than 40 years. However, a subsequent significant decrease in the incidence of invasive CBCs after the 1980s was also seen, in contrast to in situ CBCs, where the incidence stabilized in the years after.In paper III, a Traceback approach, i.e., a retrospective genetic outreach activity, was also evaluated by inviting all the women diagnosed with early-onset breast cancer, who had not previously been referred for genetic counseling, to an analysis of breast cancer predisposing genes. Pathogenic variants were identified in BRCA1 (n=2), CHEK2 (n=1), and ATM (n=1), i.e., in four (14%) of the participants. The Traceback pilot study procedure, with written pre-test information and genetic testing, followed by in-person counseling for carriers of pathogenic variants only, was well accepted. Based on these results, we will initiate an enlarged Traceback study were all previously untested women diagnosed with breast cancer between the ages of 36 and 40 years will be invited.
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| 16. |
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| 17. |
- Augustinsson, Annelie, et al.
(författare)
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Genetic testing in women with early-onset breast cancer : a Traceback pilot study
- 2021
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Ingår i: Breast Cancer Research and Treatment. - : Springer Science and Business Media LLC. - 0167-6806 .- 1573-7217. ; 190:2, s. 307-315
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Tidskriftsartikel (refereegranskat)abstract
- Purpose: In Sweden, a Traceback approach, i.e., a retrospective genetic outreach activity, among cancer patients is not normally used in clinical practice. In this pilot study, we wanted to evaluate a Traceback strategy for possible future clinical implementation and investigate why not all women with early-onset breast cancer underwent genetic testing when they were first diagnosed. Methods: Out of all women (n = 409) diagnosed with breast cancer at ≤ 35 years in Southern Sweden between 2000 and 2017, 63 had not previously been tested. These women were offered an analysis of the genes BRCA1, BRCA2, PALB2, CHEK2, and ATM through a standardized letter. Subsequently, women with normal test results were informed through a letter and carriers of pathogenic variants were contacted through a telephone call and offered in-person genetic counseling. All tested women were asked to complete a follow-up questionnaire regarding previously not having attended genetic counseling and testing and their experiences of the current retrospective approach. Results: Out of the invited women, 29 (46%) underwent genetic testing and 27 (43%) answered the questionnaire. Pathogenic variants were identified in BRCA1 (n = 2), CHEK2 (n = 1), and ATM (n = 1). The main reason for previously not having undergone genetic testing was not having received any information from their physicians. Most study participants were satisfied with both written pre- and post-test information. Conclusion: The process with retrospective identification, written pre-test information, and genetic testing, followed by in-person counseling for carriers of pathogenic variants only, was well accepted. This has implications for future Traceback implementation programs.
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| 18. |
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| 19. |
- Augustinsson, Annelie, et al.
(författare)
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Red-Haired People's Altered Responsiveness to Pain, Analgesics, and Hypnotics : Myth or Fact? A Narrative Review
- 2024
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Ingår i: Journal of Personalized Medicine. - : MDPI. - 2075-4426. ; 14:6
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Forskningsöversikt (refereegranskat)abstract
- Red hair has been linked to altered sensitivity to pain, analgesics, and hypnotics. This alteration may be impacted by variants in the melanocortin-1 receptor (MC1R) gene, which are mainly found in redheads. The aim of this narrative review was to explore and present the current state of knowledge on red hair and its plausible associations with altered responsiveness to pain, analgesics, and hypnotics. Structured searches in the PubMed, CINAHL Complete, and Scopus electronic databases were conducted. Evidence suggests that women with red hair have an increased sensitivity to pain. Conversely, data also indicate a higher pain tolerance in homozygous carriers of MC1R variant alleles. Varied responses to analgesia have been reported, with both increased analgesic responsiveness in homozygous carriers of MC1R variant alleles and less analgesia in redheads. Data indicate an increased need for hypnotics in redheads. However, failed attempts to find statistical associations between red hair and altered responsiveness to hypnotics are also evident. Even though there seems to be an association between red hair and an altered responsiveness to pain, analgesics, and/or hypnotics, the results of this narrative review are inconclusive. Further research studies with larger populations and MC1R testing are needed.
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| 20. |
- Augustinsson, Annelie, et al.
(författare)
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Red-Haired People's Altered Responsiveness to Pain, Analgesics, and Hypnotics: Myth or Fact?-A Narrative Review
- 2024
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Ingår i: JOURNAL OF PERSONALIZED MEDICINE. - : MDPI. - 2075-4426. ; 14:6
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Forskningsöversikt (refereegranskat)abstract
- Red hair has been linked to altered sensitivity to pain, analgesics, and hypnotics. This alteration may be impacted by variants in the melanocortin-1 receptor (MC1R) gene, which are mainly found in redheads. The aim of this narrative review was to explore and present the current state of knowledge on red hair and its plausible associations with altered responsiveness to pain, analgesics, and hypnotics. Structured searches in the PubMed, CINAHL Complete, and Scopus electronic databases were conducted. Evidence suggests that women with red hair have an increased sensitivity to pain. Conversely, data also indicate a higher pain tolerance in homozygous carriers of MC1R variant alleles. Varied responses to analgesia have been reported, with both increased analgesic responsiveness in homozygous carriers of MC1R variant alleles and less analgesia in redheads. Data indicate an increased need for hypnotics in redheads. However, failed attempts to find statistical associations between red hair and altered responsiveness to hypnotics are also evident. Even though there seems to be an association between red hair and an altered responsiveness to pain, analgesics, and/or hypnotics, the results of this narrative review are inconclusive. Further research studies with larger populations and MC1R testing are needed.
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