| 1. |
- Couch, Fergus J., et al.
(author)
-
AURKA F31I polymorphism and breast cancer risk in BRCA1 and BRCA2 mutation carriers: A consortium of investigators of modifiers of BRCA1/2 study
- 2007
-
In: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 16:7, s. 1416-1421
-
Journal article (peer-reviewed)abstract
- The AURKA oncogene is associated with abnormal chromosome segregation and aneuploidy and predisposition to cancer. Amplification of AURKA has been detected at higher frequency in tumors from BRCA1 and BRCA2 mutation carriers than in sporadic breast tumors, suggesting that overexpression of AURKA and inactivation of BRCA1 and BRCA2 cooperate during tumor development and progression. The F31I polymorphism in AURKA has been associated with breast cancer risk in the homozygous state in prior studies. We evaluated whether the AURKA F31I polymorphism modifies breast cancer risk in BRCA1 and BRCA2 mutation carriers from the Consortium of Investigators of Modifiers of BRCA1/2. Consortium of Investigators of Modifiers of BRCA1/2 was established to provide sufficient statistical power through increased numbers of mutation carriers to identify polymorphisms that act as modifiers of cancer risk and can refine breast cancer risk estimates in BRCA1 and BRCA2 mutation carriers. A total of 4,935 BRCA1 and 2,241 BRCA2 mutation carriers and 11 individuals carrying both BRCA1 and BRCA2 mutations was genotyped for F31I. Overall, homozygosity for the 311 allele was not significantly associated with breast cancer risk in BRCA1 and BRCA2 carriers combined [hazard ratio (HR), 0.91; 95% confidence interval (95% CI), 0.77-1.061. Similarly, no significant association was seen in BRCA1 (HR, 0.90; 95% Cl, 0.75-1.08) or BRCA2 carriers (HR, 0.93; 95% CI, 0.67-1.29) or when assessing the modifying effects of either bilateral prophylactic oophorectomy or menopausal status of BRCA1 and BRCA2 carriers. In summary, the F31I polymorphism in AURKA is not associated with a modified risk of breast cancer in BRCA1 and BRCA2 carriers.
|
|
| 2. |
- Hung, Rayjean J, et al.
(author)
-
A susceptibility locus for lung cancer maps to nicotinic acetylcholine receptor subunit genes on 15q25
- 2008
-
In: Nature. - : Nature Publishing Group. - 0028-0836 .- 1476-4687. ; 452:7187, s. 633-637
-
Journal article (peer-reviewed)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.
|
|
| 3. |
- Kotsopoulos, Joanne, et al.
(author)
-
Infertility, treatment of infertility, and the risk of breast cancer among women with BRCA1 and BRCA2 mutations : a case-control study
- 2008
-
In: Cancer Causes and Control. - : Springer Science and Business Media LLC. - 1573-7225 .- 0957-5243. ; 19:10, s. 9-1111
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Women with a breast cancer susceptibility gene 1 (BRCA1) or breast cancer susceptibility gene 2 (BRCA2) mutation are at increased risk for developing breast and ovarian cancer. Various reproductive and hormonal factors have been shown to modify the risk of breast cancer. These studies suggest that estrogen exposure and deprivation are important in the etiology of hereditary cancer. Many patients are interested in the possibility of an adverse effect of fertility treatment on breast cancer risk. It is important to evaluate whether or not infertility per se or exposure to fertility medications increase the risk of breast cancer in genetically predisposed women.METHODS: We conducted a matched case-control study of 1,380 pairs of women with a BRCA1 or BRCA2 mutation to determine if a history of infertility, the use of fertility medications, or undergoing in vitro fertilization (IVF) were associated with and increased the risk of breast cancer.RESULTS: Sixteen percent of the study subjects reported having experienced a fertility problem and 4% had used a fertility medication. Women who had used a fertility medication were not at significantly increased risk of breast cancer (odds ratio [OR] = 1.21; 95% confidence interval [CI] = 0.81-1.82) compared to non-users. Furthermore, there was no risk associated with a history of use of a fertility medication when the subjects were stratified by parity: (OR = 1.29; 95% CI = 0.83-2.01 for nulliparous women and OR = 0.81; 95% CI = 0.30-2.22 for parous women).CONCLUSIONS: The results of this study suggest that the use of fertility medications does not adversely affect the risk of breast cancer among BRCA mutation carriers. Given the small sizes of the exposed subgroups, these findings should be interpreted with caution and confirmatory studies are required.
|
|
| 4. |
|
|
| 5. |
- McKay, James D., et al.
(author)
-
Lung cancer susceptibility locus at 5p15.33
- 2008
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 40:12, s. 1404-1406
-
Journal article (peer-reviewed)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.
|
|
