Combined effect of low-penetrant SNPs on breast cancer risk.
(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)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/2221249
- author
- organization
-
- Clinical Microbiology, Malmö (research group)
- Internal Medicine - Epidemiology (research group)
- Surgery (research group)
- Family Medicine and Clinical Epidemiology (research group)
- EpiHealth: Epidemiology for Health
- BioCARE: Biomarkers in Cancer Medicine improving Health Care, Education and Innovation
- publishing date
- 2012
- type
- Contribution to journal
- publication status
- published
- subject
- in
- British Journal of Cancer
- volume
- 106
- pages
- 8 pages
- publisher
- Nature Publishing Group
- external identifiers
-
- wos:000299321100022
- pmid:22045194
- scopus:84856415225
- pmid:22045194
- ISSN
- 1532-1827
- DOI
- 10.1038/bjc.2011.461
- language
- English
- LU publication?
- yes
- id
- 981a0507-a6cb-4231-a39c-15ff21162e7f (old id 2221249)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/22045194?dopt=Abstract
- date added to LUP
- 2016-04-04 07:00:05
- date last changed
- 2022-05-16 19:26:08
@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 <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}}, doi = {{10.1038/bjc.2011.461}}, volume = {{106}}, year = {{2012}}, }