| 1. |
- Hung, Rayjean J, et al.
(författare)
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A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25
- 2008
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Ingår i: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 452:7187, s. 633-637
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Tidskriftsartikel (refereegranskat)abstract
- Lung cancer is the most common cause of cancer death worldwide, with over one million cases annually. To identify genetic factors that modify disease risk, we conducted a genome-wide association study by analysing 317,139 single-nucleotide polymorphisms in 1,989 lung cancer cases and 2,625 controls from six central European countries. We identified a locus in chromosome region 15q25 that was strongly associated with lung cancer (P = 9 x 10(-10)). This locus was replicated in five separate lung cancer studies comprising an additional 2,513 lung cancer cases and 4,752 controls (P = 5 x 10(-20) overall), and it was found to account for 14% (attributable risk) of lung cancer cases. Statistically similar risks were observed irrespective of smoking status or propensity to smoke tobacco. The association region contains several genes, including three that encode nicotinic acetylcholine receptor subunits (CHRNA5, CHRNA3 and CHRNB4). Such subunits are expressed in neurons and other tissues, in particular alveolar epithelial cells, pulmonary neuroendocrine cells and lung cancer cell lines, and they bind to N'-nitrosonornicotine and potential lung carcinogens. A non-synonymous variant of CHRNA5 that induces an amino acid substitution (D398N) at a highly conserved site in the second intracellular loop of the protein is among the markers with the strongest disease associations. Our results provide compelling evidence of a locus at 15q25 predisposing to lung cancer, and reinforce interest in nicotinic acetylcholine receptors as potential disease candidates and chemopreventative targets.
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| 2. |
- Lindemann, Kristina, et al.
(författare)
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Serum lipids and endometrial cancer risk: results from the HUNT-II study.
- 2009
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Ingår i: International journal of cancer. Journal international du cancer. - : Wiley. - 1097-0215. ; 124:12, s. 2938-41
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Tidskriftsartikel (refereegranskat)abstract
- Obesity is a major risk factor for endometrial cancer. Still, the association of obesity-related metabolic factors, such as serum lipids and lipoprotein levels, is unclear. We prospectively examined the association of serum levels of triglycerides, total cholesterol, low-density lipoprotein cholesterol, non-high-density lipoprotein (non-HDL), and HDL cholesterol with endometrial cancer risk among 31,473 women. During 9 years of follow-up, 100 cases of endometrial cancer were identified by linkage to the Cancer Registry of Norway. There was a positive association of serum triglyceride levels with endometrial cancer risk. Comparing the highest to the lowest quartile of triglycerides, the age-adjusted hazard ratio was 2.34 (95% CI: 1.04-5.28), and further adjustment for body mass index attenuated the association (hazard ratio 1.79, 95% CI: 0.79-4.05). For total serum cholesterol, low-density lipoprotein cholesterol and HDL cholesterol there were no associations with endometrial cancer risk, either without or after adjustment for body mass index. Serum triglyceride levels were positively associated with the risk of endometrial cancer, and some of the association seems to be attributable to obesity. Apart from higher estrogen levels produced in adipose tissue, mechanisms more specifically related to triglycerides may also be involved in endometrial cancer. Further prospective studies on this subject are needed to better understand the association of blood lipids with endometrial cancer risk.
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| 3. |
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| 4. |
- McKay, James D., et al.
(författare)
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Lung cancer susceptibility locus at 5p15.33
- 2008
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 40:12, s. 1404-1406
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Tidskriftsartikel (refereegranskat)abstract
- We carried out a genome-wide association study of lung cancer (3,259 cases and 4,159 controls), followed by replication in 2,899 cases and 5,573 controls. Two uncorrelated disease markers at 5p15.33, rs402710 and rs2736100 were detected by the genome-wide data (P - 2 x 10(-7) and P = 4 x 10(-6)) and replicated by the independent study series (P = 7 x 10(-5) and P = 0.016). The susceptibility region contains two genes, TERT and CLPTM1L, suggesting that one or both may have a role in lung cancer etiology.
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| 5. |
- Yeager, Meredith, et al.
(författare)
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Identification of a new prostate cancer susceptibility locus on chromosome 8q24.
- 2009
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 41:10, s. 1055-7
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Tidskriftsartikel (refereegranskat)abstract
- We report a genome-wide association study in 10,286 cases and 9,135 controls of European ancestry in the Cancer Genetic Markers of Susceptibility (CGEMS) initiative. We identify a new association with prostate cancer risk on chromosome 8q24 (rs620861, P = 1.3 x 10(-10), heterozygote OR = 1.17, 95% CI 1.10-1.24; homozygote OR = 1.33, 95% CI 1.21-1.45). This defines a new locus associated with prostate cancer susceptibility on 8q24.
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