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Sökning: onr:"swepub:oai:lup.lub.lu.se:981a0507-a6cb-4231-a39c-15ff21162e7f" > Combined effect of ...

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

Harlid, Sophia, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Klinisk mikrobiologi, Malmö, Clinical Microbiology, Malmö
Ivarsson, M I L (författare)
Butt, Salma, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Kirurgi, Surgery, Internmedicin - epidemiologi, Internal Medicine - Epidemiology
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Grzybowska, E (författare)
Eyfjörd, J E (författare)
Lenner, P (författare)
Försti, Asta, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Allmänmedicin och klinisk epidemiologi, Family Medicine and Clinical Epidemiology
Hemminki, Kari, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Allmänmedicin och klinisk epidemiologi, Family Medicine and Clinical Epidemiology
Manjer, Jonas, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Kirurgi, Surgery
Dillner, Joakim, (författare)
Forskargrupper vid Lunds universitet, Lund University Research Groups, Lunds universitet, Lund University, Klinisk mikrobiologi, Malmö, Clinical Microbiology, Malmö
Carlson, J (författare)
Harlid, S (författare)
Butt, S (författare)
Eyfjord, JE (författare)
Forsti, A (författare)
Hemminki, K (författare)
Manjer, J (författare)
Dillner, J, (författare)
Karolinska Institutet
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2012
Engelska.
Ingår i: British Journal of Cancer. - Nature Publishing Group. - 1532-1827. ; 106, s. 389-396
  • Tidskriftsartikel (refereegranskat)
Abstract Ämnesord
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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 × 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Klinisk medicin -- Cancer och onkologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES  -- Clinical Medicine -- Cancer and Oncology (hsv//eng)

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