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Combined effect of low-penetrant SNPs on breast cancer risk.

Harlid, Sophia LU ; Ivarsson, M I L; Butt, Salma LU ; Grzybowska, E; Eyfjörd, J E; Lenner, P; Försti, Asta LU ; Hemminki, Kari LU ; Manjer, Jonas LU and Dillner, Joakim LU , et al. (2012) In British Journal of Cancer 106. p.389-396
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... (More)
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 × 10(-20) and 1.5 × 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 × 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 advance online publication, 1 November 2011; doi:10.1038/bjc.2011.461 www.bjcancer.com. (Less)
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British Journal of Cancer
volume
106
pages
389 - 396
publisher
Nature Publishing Group
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  • wos:000299321100022
  • pmid:22045194
  • scopus:84856415225
ISSN
1532-1827
DOI
10.1038/bjc.2011.461
language
English
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yes
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981a0507-a6cb-4231-a39c-15ff21162e7f (old id 2221249)
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http://www.ncbi.nlm.nih.gov/pubmed/22045194?dopt=Abstract
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2011-12-02 18:52:44
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@article{981a0507-a6cb-4231-a39c-15ff21162e7f,
  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 &lt;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 × 10(-20) and 1.5 × 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 × 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 advance online publication, 1 November 2011; doi:10.1038/bjc.2011.461 www.bjcancer.com.},
  author       = {Harlid, Sophia and Ivarsson, M I L and Butt, Salma and Grzybowska, E and Eyfjörd, J E and Lenner, P and Försti, Asta and Hemminki, Kari and Manjer, Jonas and Dillner, Joakim and Carlson, J},
  issn         = {1532-1827},
  language     = {eng},
  pages        = {389--396},
  publisher    = {Nature Publishing Group},
  series       = {British Journal of Cancer},
  title        = {Combined effect of low-penetrant SNPs on breast cancer risk.},
  url          = {http://dx.doi.org/10.1038/bjc.2011.461},
  volume       = {106},
  year         = {2012},
}