| 1. |
- Butt, Salma, et al.
(författare)
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Genetic predisposition, parity, age at first childbirth and risk for breast cancer.
- 2012
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Ingår i: BMC Research Notes. - : Springer Science and Business Media LLC. - 1756-0500. ; 5
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Recent studies have identified several single-nucleotide polymorphisms (SNPs) associated with the risk of breast cancer and parity and age at first childbirth are well established and important risk factors for breast cancer. The aim of the present study was to examine the interaction between these environmental factors and genetic variants on breast cancer risk.METHODS: The Malmö Diet and Cancer Study (MDCS) included 17 035 female participants, from which 728 incident breast cancer cases were matched to 1448 controls. The associations between 14 SNPs and breast cancer risk were investigated in different strata of parity and age at first childbirth. A logistic regression analysis for the per allele risk, adjusted for potential confounders yielded odds ratios (OR) with 95% confidence intervals (CI).RESULTS: Six of the previously identified SNPs showed a statistically significant association with breast cancer risk: rs2981582 (FGFR2), rs3803662 (TNRC9), rs12443621 (TNRC9), rs889312 (MAP3K1), rs3817198 (LSP1) and rs2107425 (H19). We could not find any statistically significant interaction between the effects of tested SNPs and parity/age at first childbirth on breast cancer risk after adjusting for multiple comparisons.CONCLUSIONS: The results of this study are in agreement with previous studies of null interactions between tested SNPs and parity/age at first childbirth with regard to breast cancer risk.
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| 2. |
- Hansson, Mats G, et al.
(författare)
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Should donors be allowed to give broad consent to future biobank research?
- 2006
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Ingår i: The Lancet Oncology. - 1474-5488 .- 1470-2045. ; 7:3, s. 266-9
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Tidskriftsartikel (refereegranskat)abstract
- Large international biobank studies can make substantial contributions to scientific research by validation of the biological importance of previous research and by identification of previously unknown causes of disease. However, regulations for patient consent that are too strict and discrepancies in national policies on informed consent might hinder progress. Therefore, establishment of common ground for ethical review of biobank research is essential. in this essay, broad consent is defined on a scale between strictly specified (eg, for a specific study) and blanket consent (ie, with no restrictions regarding the purpose of the research). Future research includes that which might not be planned or even conceptualised when consent is obtained. In conclusion, broad consent and consent for future research are valid ethically and should be recommended for biobank research provided that: personal information related to research is handled safely; donors of biological samples are granted the right to withdraw consent; and new research studies or changes to the legal or ethical authority of a biobank are approved by an ethics-review board.
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| 3. |
- Harlid, Sophia, 1978-, et al.
(författare)
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A candidate CpG SNP approach identifies a breast cancer associated ESR1-SNP
- 2011
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Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 129:7, s. 1689-1698
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Tidskriftsartikel (refereegranskat)abstract
- Altered DNA methylation is often seen in malignant cells, potentially contributing to carcinogenesis by suppressing gene expression. We hypothesized that heritable methylation potential might be a risk factor for breast cancer and evaluated possible association with breast cancer for single nucleotide polymorphisms (SNPs) either involving CpG sequences in extended 5'-regulatory regions of candidate genes (ESR1, ESR2, PGR, and SHBG) or CpG and missense coding SNPs in genes involved in methylation (MBD1, MECP2, DNMT1, MGMT, MTHFR, MTR, MTRR, MTHFD1, MTHFD2, BHMT, DCTD, and SLC19A1). Genome-wide searches for genetic risk factors for breast cancers have in general not investigated these SNPs, because of low minor allele frequency or weak haplotype associations. Genotyping was performed using Mass spectrometry-Maldi-Tof in a screening panel of 538 cases and 1,067 controls. Potential association to breast cancer was identified for 15 SNPs and one of these SNPs (rs7766585 in ESR1) was found to associate strongly with breast cancer, OR 1.30 (95% CI 1.17-1.45; p-value 2.1 × 10(-6) ), when tested in a verification panel consisting of 3,211 unique breast cancer cases and 4,223 unique controls from five European biobank cohorts. In conclusion, a candidate gene search strategy focusing on methylation-related SNPs did identify a SNP that associated with breast cancer at high significance.
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| 4. |
- Harlid, Sophia, 1978-, et al.
(författare)
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Combined effect of low-penetrant SNPs on breast cancer risk
- 2012
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Ingår i: British Journal of Cancer. - London : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 106:2, s. 389-396
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although many low-penetrant genetic risk factors for breast cancer have been discovered, knowledge about the effect of multiple risk alleles is limited, especially in women <50 years. We therefore investigated the association between multiple risk alleles and breast cancer risk as well as individual effects according to age-approximated pre- and post-menopausal status.METHODS: Ten previously described breast cancer-associated single-nucleotide polymorphisms (SNPs) were analysed in a joint European biobank-based study comprising 3584 breast cancer cases and 5063 cancer-free controls. Genotyping was performed using MALDI-TOF mass spectrometry, and odds ratios were estimated using logistic regression.RESULTS: Significant associations with breast cancer were confirmed for 7 of the 10 SNPs. Analysis of the joint effect of the original 10 as well as the statistically significant 7 SNPs (rs2981582, rs3803662, rs889312, rs13387042, rs13281615, rs3817198 and rs981782) found a highly significant trend for increasing breast cancer risk with increasing number of risk alleles (P-trend 5.6 x 10(-20) and 1.5 x 10(-25), respectively). Odds ratio for breast cancer of 1.84 (95% confidence interval (CI): 1.59-2.14; 10 SNPs) and 2.12 (95% CI: 1.80-2.50; 7 SNPs) was seen for the maximum vs the minimum number of risk alleles. Additionally, one of the examined SNPs (rs981782 in HCN1) had a protective effect that was significantly stronger in premenopausal women (P-value: 7.9 x 10(-4)).CONCLUSION: The strongly increasing risk seen when combining many low-penetrant risk alleles supports the polygenic inheritance model of breast cancer. British Journal of Cancer (2012) 106, 389-396. doi:10.1038/bjc.2011.461 www.bjcancer.com Published online 1 November 2011 (C) 2012 Cancer Research UK
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| 5. |
- Harlid, Sophia, 1978-, et al.
(författare)
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Interactive effect of genetic susceptibility with height, body mass index, and hormone replacement therapy on the risk of breast cancer.
- 2012
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Ingår i: BMC Women's Health. - : Springer Science and Business Media LLC. - 1472-6874. ; 12
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Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Breast cancer today has many established risk factors, both genetic and environmental, but these risk factors by themselves explain only part of the total cancer incidence. We have investigated potential interactions between certain known genetic and phenotypic risk factors, specifically nine single nucleotide polymorphisms (SNPs) and height, body mass index (BMI) and hormone replacement therapy (HRT).METHODS: We analyzed samples from three different study populations: two prospectively followed Swedish cohorts and one Icelandic case-control study. Totally 2884 invasive breast cancer cases and 4508 controls were analysed in the study. Genotypes were determined using Mass spectrometry-Maldi-TOF and phenotypic variables were derived from measurements and/or questionnaires. Odds Ratios and 95% confidence intervals were calculated using unconditional logistic regression with the inclusion of an interaction term in the logistic regression model.RESULTS: One SNP (rs851987 in ESR1) tended to interact with height, with an increasingly protective effect of the major allele in taller women (p = 0.007) and rs13281615 (on 8q24) tended to confer risk only in non users of HRT (p-for interaction = 0.03). There were no significant interactions after correction for multiple testing.CONCLUSIONS: We conclude that much larger sample sets would be necessary to demonstrate interactions between low-risk genetic polymorphisms and the phenotypic variables height, BMI and HRT on the risk for breast cancer. However the present hypothesis-generating study has identified tendencies that would be of interest to evaluate for gene-environment interactions in independent materials.
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| 7. |
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| 8. |
- Sjöholm, Malin, et al.
(författare)
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Assessing Quality and Functionality of DNA from Fresh and Archival Dried Blood Spots and Recommendations for Quality Control Guidelines.
- 2007
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Ingår i: Clinical Chemistry. - : Oxford University Press (OUP). - 0009-9147 .- 1530-8561. ; 53, s. 1401-1407
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Tidskriftsartikel (refereegranskat)abstract
- Background: Dried blood spots (DBS) are a convenient and inexpensive method for biobanking. Although many countries have established population-based DBS biobanks from neonatal screening programs, the quality and usefulness of DNA from DBS have not been extensively assessed. Methods: We compared 4 common DNA extraction methods (Qiagen, EZNA, Chelex 100, and alkaline lysis) in a pilot study using fresh DBS with known lymphocyte count. We assessed suitability for multiple displacement amplification (MDA) and subsequent single-nucleotide polymorphism (SNP) analyses. We selected the EZNA method for DNA extraction from archival samples up to 27 years old, stored at room temperature or –20 °C, and SNP analyses were performed after MDA. Results: Extraction using alkaline lysis failed in most tests, and Chelex 100 was unsuccessful in real-time PCR, whereas the EZNA and Qiagen methods were successful by all evaluated quality indices. DNA extraction by EZNA, MDA, and SNP analyses were successful for the archival samples stored at –20 °C. Conclusion: Routine protocols for evaluation of the quality and functional integrity of DNA based on DNA yield, DNA size, and quantification of amplifiable DNA allow use of sufficient template for MDA and successful SNP analyses from both primary DBS extract and MDA product. A single 3-mm disc can yield sufficient DNA for several thousand SNP analyses. DNA from DBS is thus suitable for genetic epidemiology studies.
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| 9. |
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| 10. |
- Sjöholm, Malin, et al.
(författare)
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Multiplex detection of human herpesviruses from archival specimens by using matrix-assisted laser desorption ionization-time of flight mass spectrometry.
- 2008
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Ingår i: Journal of Clinical Microbiology. - 1098-660X. ; 46:2, s. 540-545
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Tidskriftsartikel (refereegranskat)abstract
- The human herpesviruses are involved in a variety of diseases. Large-scale evaluation of the clinical and epidemiological importance of different herpesviruses requires high-throughput methods. Matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) is a method that has a multiplex capacity enabling simultaneous detection of several viruses in a single sample. PCR-based methods for the multiplex detection of all known human herpesviruses were developed on the MALDI-TOF MS system. A variety of 882 archival samples, including bronchoalveolar lavage, conjunctival fluid, sore secretion, blister material, plasma, serum, and urine, analyzed for herpesviruses using PCR-based reference methods, were used to evaluate the MALDI-TOF MS method. The overall concordance rate between the MALDI-TOF MS method and the reference methods was 95.6% (kappa = 0.90). In summary, the MALDI-TOF MS method is well suited for large-scale detection of all known human herpesviruses in a wide variety of archival biological specimens.
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