| 1. |
- Purrington, Kristen S., et al.
(författare)
-
Genome-wide association study identifies 25 known breast cancer susceptibility loci as risk factors for triple-negative breast cancer
- 2014
-
Ingår i: Carcinogenesis. - : Oxford University Press (OUP). - 0143-3334 .- 1460-2180. ; 35:5, s. 1012-1019
-
Tidskriftsartikel (refereegranskat)abstract
- In a genome-wide scan, we show that 30 variants in 25 genomic regions are associated with risk of TN breast cancer. Women carrying many of the risk variants may have 4-fold increased risk relative to women with few variants.Triple-negative (TN) breast cancer is an aggressive subtype of breast cancer associated with a unique set of epidemiologic and genetic risk factors. We conducted a two-stage genome-wide association study of TN breast cancer (stage 1: 1529 TN cases, 3399 controls; stage 2: 2148 cases, 1309 controls) to identify loci that influence TN breast cancer risk. Variants in the 19p13.1 and PTHLH loci showed genome-wide significant associations (P < 5 x 10(-) (8)) in stage 1 and 2 combined. Results also suggested a substantial enrichment of significantly associated variants among the single nucleotide polymorphisms (SNPs) analyzed in stage 2. Variants from 25 of 74 known breast cancer susceptibility loci were also associated with risk of TN breast cancer (P < 0.05). Associations with TN breast cancer were confirmed for 10 loci (LGR6, MDM4, CASP8, 2q35, 2p24.1, TERT-rs10069690, ESR1, TOX3, 19p13.1, RALY), and we identified associations with TN breast cancer for 15 additional breast cancer loci (P < 0.05: PEX14, 2q24.1, 2q31.1, ADAM29, EBF1, TCF7L2, 11q13.1, 11q24.3, 12p13.1, PTHLH, NTN4, 12q24, BRCA2, RAD51L1-rs2588809, MKL1). Further, two SNPs independent of previously reported signals in ESR1 [rs12525163 odds ratio (OR) = 1.15, P = 4.9 x 10(-) (4)] and 19p13.1 (rs1864112 OR = 0.84, P = 1.8 x 10(-) (9)) were associated with TN breast cancer. A polygenic risk score (PRS) for TN breast cancer based on known breast cancer risk variants showed a 4-fold difference in risk between the highest and lowest PRS quintiles (OR = 4.03, 95% confidence interval 3.46-4.70, P = 4.8 x 10(-) (69)). This translates to an absolute risk for TN breast cancer ranging from 0.8% to 3.4%, suggesting that genetic variation may be used for TN breast cancer risk prediction.
|
|
| 2. |
- Goodfellow, Bradley W., et al.
(författare)
-
Depth and character of rock weathering across a basaltic-hosted climosequence on Hawai` i
- 2014
-
Ingår i: Earth Surface Processes and Landforms. - : Wiley. - 0197-9337 .- 1096-9837. ; 39:3, s. 381-398
-
Tidskriftsartikel (refereegranskat)abstract
- Using field observations and geochemical and digital terrain analyses, we describe the structure and thickness of the regolith across a climosequence on the island of Hawaii to gain insight into the relative roles of precipitation and the near-surface hydrologic structure in determining weathering patterns. In the wet portion of the climosequence, where the long-term water balance is positive, the regolith thickness reaches an observed maximum of similar to 40m and appears limited by the geomorphic base-level of the landscape. However, even within this thick regolith, distinct units of varying weathering intensity occur; the vertical ordering of which largely reflects differences in the initial permeability structure of the basalt flows rather than a systematic decrease in weathering intensity downwards from the ground surface. In the dry portion of the climosequence, where the long-term water balance is negative, the regolith thickness is confined to similar to 1m, is highly dependent on the inferred permeability structure of the basalt flows, and is independent of geomorphic base-level. Weathering intensity also varies according to permeability structure and decreases in this thin regolith with distance beneath the ground surface. The abrupt change in regolith depth and character that coincides with the transition from net-positive to net-negative long-term water balance implies that small changes in precipitation rates around a neutral water balance result in large changes in the distribution and depth of weathering. Together our observations indicate that the distribution and depth of weathering in basalts (and probably other lithologies) might be best understood by considering how precipitation interacts with the complicated near-surface permeability structure over regolith-forming timescales to weather rock in the vadose zone.
|
|
