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- McMaster, ML, et al.
(författare)
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Two high-risk susceptibility loci at 6p25.3 and 14q32.13 for Waldenström macroglobulinemia
- 2018
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Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 9:1, s. 4182-
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Tidskriftsartikel (refereegranskat)abstract
- Waldenström macroglobulinemia (WM)/lymphoplasmacytic lymphoma (LPL) is a rare, chronic B-cell lymphoma with high heritability. We conduct a two-stage genome-wide association study of WM/LPL in 530 unrelated cases and 4362 controls of European ancestry and identify two high-risk loci associated with WM/LPL at 6p25.3 (rs116446171, near EXOC2 and IRF4; OR = 21.14, 95% CI: 14.40–31.03, P = 1.36 × 10−54) and 14q32.13 (rs117410836, near TCL1; OR = 4.90, 95% CI: 3.45–6.96, P = 8.75 × 10−19). Both risk alleles are observed at a low frequency among controls (~2–3%) and occur in excess in affected cases within families. In silico data suggest that rs116446171 may have functional importance, and in functional studies, we demonstrate increased reporter transcription and proliferation in cells transduced with the 6p25.3 risk allele. Although further studies are needed to fully elucidate underlying biological mechanisms, together these loci explain 4% of the familial risk and provide insights into genetic susceptibility to this malignancy.
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| 5. |
- Goldin, LR, et al.
(författare)
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Autoimmunity and lymphomagenesis
- 2009
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Ingår i: International journal of cancer. - : Wiley. - 1097-0215 .- 0020-7136. ; 124:7, s. 1497-1502
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Tidskriftsartikel (refereegranskat)
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| 9. |
- Goldin, LR, et al.
(författare)
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Familial risk of lymphoproliferative tumors in families of patients with chronic lymphocytic leukemia: results from the Swedish Family-Cancer Database
- 2004
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Ingår i: Blood. - : American Society of Hematology. - 0006-4971 .- 1528-0020. ; 104:6, s. 1850-1854
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Tidskriftsartikel (refereegranskat)abstract
- The importance of genetic factors in etiology of chronic lymphocytic leukemia (CLL) is suggested by family and population studies. However, the spectrum of malignancies sharing common genetic factors with CLL and the effects of sex and age on familial risk are unknown. We used the Swedish Family-Cancer Database to test for increased familial risks of CLL and other lymphoproliferative tumors. Cancer diagnoses from 1958 to 1998 were assessed in 14 336 first-degree relatives of 5918 CLL cases and in 28 876 first-degree relatives of 11 778 controls. Cancer risks in relatives of cases were compared with those in relatives of controls using marginal survival models. Relatives of cases were at significantly increased risk for CLL (relative risk [RR] = 7.52; 95% confidence interval [CI], 3.63-15.56), for non-Hodgkin lymphoma (RR = 1.45; 95% CI, 0.98-2.16), and for Hodgkin lymphoma (RR = 2.35; 95% CI, 1.08-5.08). CLL risks were similar in parents, siblings, and offspring of cases, in male and female relatives, and were not affected by the case's age at diagnosis. Anticipation was not significant when analyzed using life table methods. We conclude that the familial component of CLL is shared with other lymphoproliferative malignances, suggesting common genetic pathways. However, because clinically diagnosed CLL is uncommon, absolute excess risk to relatives is small.
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