| 1. |
- Broderick, Peter, et al.
(författare)
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Common variation at 3p22.1 and 7p15.3 influences multiple myeloma risk
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:1, s. 58-83
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Tidskriftsartikel (refereegranskat)abstract
- To identify risk variants for multiple myeloma, we conducted a genome-wide association study of 1,675 individuals with multiple myeloma and 5,903 control subjects. We identified risk loci for multiple myeloma at 3p22.1 (rs1052501 in ULK4; odds ratio (OR) = 1.32; P = 7.47 x 10(-9)) and 7p15.3 (rs4487645, OR = 1.38; P = 3.33 x 10(-15)). In addition, we observed a promising association at 2p23.3 (rs6746082, OR = 1.29; P = 1.22 x 10(-7)). Our study identifies new genomic regions associated with multiple myeloma risk that may lead to new etiological insights.
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| 2. |
- Enciso-Mora, Victor, et al.
(författare)
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A genome-wide association study of Hodgkin's lymphoma identifies new susceptibility loci at 2p16.1 (REL), 8q24.21 and 10p14 (GATA3)
- 2010
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1126-1130
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Tidskriftsartikel (refereegranskat)abstract
- To identify susceptibility loci for classical Hodgkin's lymphoma (cHL), we conducted a genome-wide association study of 589 individuals with cHL (cases) and 5,199 controls with validation in four independent samples totaling 2,057 cases and 3,416 controls. We identified three new susceptibility loci at 2p16.1 (rs1432295, REL, odds ratio (OR) = 1.22, combined P = 1.91 × 10−8), 8q24.21 (rs2019960, PVT1, OR = 1.33, combined P = 1.26 × 10−13) and 10p14 (rs501764, GATA3, OR = 1.25, combined P = 7.05 × 10−8). Furthermore, we confirmed the role of the major histocompatibility complex in disease etiology by revealing a strong human leukocyte antigen (HLA) association (rs6903608, OR = 1.70, combined P = 2.84 × 10−50). These data provide new insight into the pathogenesis of cHL.
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| 3. |
- Klimosch, Sascha N., et al.
(författare)
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Functional TLR5 Genetic Variants Affect Human Colorectal Cancer Survival
- 2013
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Ingår i: Cancer Research. - 1538-7445. ; 73:24, s. 7232-7242
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Tidskriftsartikel (refereegranskat)abstract
- Toll-like receptors (TLR) are overexpressed on many types of cancer cells, including colorectal cancer cells, but little is known about the functional relevance of these immune regulatory molecules in malignant settings. Here, we report frequent single-nucleotide polymorphisms (SNP) in the flagellin receptor TLR5 and the TLR downstream effector molecules MyD88 and TIRAP that are associated with altered survival in a large cohort of Caucasian patients with colorectal cancer (n = 613). MYD88 rs4988453, a SNP that maps to a promoter region shared with the acetyl coenzyme-A acyl-transferase-1 (ACAA1), was associated with decreased survival of patients with colorectal cancer and altered transcriptional activity of the proximal genes. In the TLR5 gene, rs5744174/F616L was associated with increased survival, whereas rs2072493/N592S was associated with decreased survival. Both rs2072493/N592S and rs5744174/F616L modulated TLR5 signaling in response to flagellin or to different commensal and pathogenic intestinal bacteria. Notably, we observed a reduction in flagellin-induced p38 phosphorylation, CD62L shedding, and elevated expression of interleukin (IL)-6 and IL-1 beta mRNA in human primary immune cells from TLR5 616LL homozygote carriers, as compared with 616FF carriers. This finding suggested that the well-documented effect of cytokines like IL-6 on colorectal cancer progression might be mediated by TLR5 genotype-dependent flagellin sensing. Our results establish an important link between TLR signaling and human colorectal cancer with relevance for biomarker and therapy development. (C)2013 AACR.
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| 4. |
- Mousavi, Seyed Mohsen, et al.
(författare)
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Ethnic differences in breast cancer risk and survival: A study on immigrants in Sweden
- 2013
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Ingår i: Acta Oncologica. - 1651-226X. ; 52:8, s. 1637-1642
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Tidskriftsartikel (refereegranskat)abstract
- Background. There are large geographic differences in breast cancer risk but whether survival differs between low- and high-risk groups is less well-established. As the survival of cancer depends on the level of healthcare and awareness of disease risks, subtle differences in cancer biology cannot be revealed in international comparisons. Instead, comparison of diverse immigrant groups in a country of uniformly accessible healthcare system should enable conclusions to be made about ethnic determinants of cancer risk and survival. Material and methods. The Swedish Family-Cancer Database was used to calculate standardized incidence (SIRs) and hazard ratios (HRs) of death from female breast cancer in 12 505 and 137 547 patients diagnosed with breast cancer among immigrants and Swedes, respectively. The ratios were adjusted for age, period, region, parity, and age at first childbirth. Ordinal logistic regression analysis was used to estimate odds ratios (ORs) for the clinical TNM classes. The analyses were stratified by menopausal status and histology. Results. Turks, Southeast Asians, and Chileans had the lowest breast cancer risk (SIR = 0.44; 95% CI 0.37-0.51) and Iraqis the highest risk (1.19; 1.05-1.35), mainly due to premenopausal cancer (1.51; 1.27-1.78). The HRs for all breast cancers were between 0.98 (0.81-1.18) (low-risk Europeans) and 1.24 (0.94-1.63) (lowest-risk non-Europeans), but were not significant. No differences in survival of ductal carcinoma between immigrants and Swedes were found, while low-risk non-Europeans had a HR of 2.88 (1.37-6.08) for lobular carcinoma. Low-risk non-Europeans were diagnosed in a higher T-class (OR = 1.87; 1.21-2.87) than Swedes. Conclusion. We did not find any evidence that ethnic differences in breast cancer risk substantially affect the survival. The observed poor survival of some low-risk immigrants in lobular carcinoma may be related to treatment. The tendency of low-risk immigrants to present with higher T-class compared to Swedes may depend on their lower participation in the mammography screening program.
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