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Combined effect of ...
Combined effect of low-penetrant SNPs on breast cancer risk
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- Harlid, Sophia, 1978- (author)
- Lund University,Lunds universitet,Klinisk mikrobiologi, Malmö,Forskargrupper vid Lunds universitet,Clinical Microbiology, Malmö,Lund University Research Groups
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Ivarsson, Malin I. L. (author)
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- Butt, Salma (author)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Internmedicin - epidemiologi,Surgery,Lund University Research Groups,Internal Medicine - Epidemiology
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Grzybowska, Eva (author)
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Eyfjord, Jorunn E. (author)
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Lenner, Per (author)
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- Försti, Asta (author)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups
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- Hemminki, Kari (author)
- Lund University,Lunds universitet,Allmänmedicin och klinisk epidemiologi,Forskargrupper vid Lunds universitet,Family Medicine and Clinical Epidemiology,Lund University Research Groups
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- Manjer, Jonas (author)
- Lund University,Lunds universitet,Kirurgi,Forskargrupper vid Lunds universitet,Surgery,Lund University Research Groups
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- Dillner, Joakim (author)
- Karolinska Institutet,Lund University,Lunds universitet,Klinisk mikrobiologi, Malmö,Forskargrupper vid Lunds universitet,Clinical Microbiology, Malmö,Lund University Research Groups
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Carlson, Joyce (author)
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(creator_code:org_t)
- 2011-11-01
- 2012
- English.
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In: British Journal of Cancer. - London : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 106:2, s. 389-396
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Abstract
Subject headings
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- 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
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Clinical Medicine -- Cancer and Oncology (hsv//eng)
Keyword
- breast cancer
- hereditability
- common variants
- multiple risk-allele GWA replication
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Harlid, Sophia, ...
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Ivarsson, Malin ...
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Butt, Salma
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Grzybowska, Eva
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Eyfjord, Jorunn ...
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Lenner, Per
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show more...
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Försti, Asta
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Hemminki, Kari
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Manjer, Jonas
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Dillner, Joakim
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Carlson, Joyce
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Clinical Medicin ...
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and Cancer and Oncol ...
- Articles in the publication
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British Journal ...
- By the university
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Umeå University
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Lund University
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Karolinska Institutet