The KL-VS sequence variant of Klotho and cancer risk in BRCA1 and BRCA2 mutation carriers Journal Article
| Authors: | Laitman, Y.; Kuchenbaecker, K. B.; Rantala, J.; Hogervorst, F.; Peock, S.; Godwin, A. K.; Arason, A.; Kirchhoff, T.; Offit, K.; Isaacs, C.; Schmutzler, R. K.; Wappenschmidt, B.; Nevanlinna, H.; Chen, X.; Chenevix-Trench, G.; Healey, S.; Couch, F.; Peterlongo, P.; Radice, P.; Nathanson, K. L.; Caligo, M. A.; Neuhausen, S. L.; Ganz, P.; Sinilnikova, O. M.; McGuffog, L.; Easton, D. F.; Antoniou, A. C.; Wolf, I.; Friedman, E. |
| Article Title: | The KL-VS sequence variant of Klotho and cancer risk in BRCA1 and BRCA2 mutation carriers |
| Abstract: | Klotho (KL) is a putative tumor suppressor gene in breast and pancreatic cancers located at chromosome 13q12. A functional sequence variant of Klotho (KL-VS) was previously reported to modify breast cancer risk in Jewish BRCA1 mutation carriers. The effect of this variant on breast and ovarian cancer risks in non-Jewish BRCA1/BRCA2 mutation carriers has not been reported. The KL-VS variant was genotyped in women of European ancestry carrying a BRCA mutation: 5,741 BRCA1 mutation carriers (2,997 with breast cancer, 705 with ovarian cancer, and 2,039 cancer free women) and 3,339 BRCA2 mutation carriers (1,846 with breast cancer, 207 with ovarian cancer, and 1,286 cancer free women) from 16 centers. Genotyping was accomplished using TaqMan ® allelic discrimination or matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Data were analyzed within a retrospective cohort approach, stratified by country of origin and Ashkenazi Jewish origin. The per-allele hazard ratio (HR) for breast cancer was 1.02 (95% CI 0.93-1.12, P = 0.66) for BRCA1 mutation carriers and 0.92 (95% CI 0.82-1.04, P = 0.17) for BRCA2 mutation carriers. Results remained unaltered when analysis excluded prevalent breast cancer cases. Similarly, the per-allele HR for ovarian cancer was 1.01 (95% CI 0.84-1.20, P = 0.95) for BRCA1 mutation carriers and 0.9 (95% CI 0.66-1.22, P = 0.45) for BRCA2 mutation carriers. The risk did not change when carriers of the 6174delT mutation were excluded. There was a lack of association of the KL-VS Klotho variant with either breast or ovarian cancer risk in BRCA1 and BRCA2 mutation carriers. © Springer Science+Business Media, LLC. 2011. |
| Keywords: | adult; controlled study; aged; middle aged; gene mutation; major clinical study; single nucleotide polymorphism; case control study; genetics; case-control studies; polymorphism, single nucleotide; cancer risk; ovarian neoplasms; genetic predisposition to disease; ovary cancer; breast cancer; proportional hazards models; cohort analysis; genetic association; genetic variability; genotype; gene frequency; breast neoplasms; brca1 protein; brca2 protein; heterozygote; retrospective study; tumor suppressor gene; proportional hazards model; genetic susceptibility; breast tumor; ovary tumor; matrix assisted laser desorption ionization time of flight mass spectrometry; genetic predisposition; brca; ethnic group; brca1 protein, human; penetrance; beta glucuronidase; glucuronidase; genetic association studies; ashkenazi jew; ovarian cancer-klotho; modifier gene; kotho vs gene; mutation carrier; brca2 protein, human; klotho protein |
| Journal Title: | Breast Cancer Research and Treatment |
| Volume: | 132 |
| Issue: | 3 |
| ISSN: | 0167-6806 |
| Publisher: | Springer |
| Date Published: | 2012-04-01 |
| Start Page: | 1119 |
| End Page: | 1126 |
| Language: | English |
| DOI: | 10.1007/s10549-011-1938-8 |
| PROVIDER: | scopus |
| PMCID: | PMC3352679 |
| PUBMED: | 22212556 |
| DOI/URL: | |
| Notes: | --- - "Export Date: 9 January 2013" - "CODEN: BCTRD" - "Source: Scopus" |
