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Who gets cancer?
Breast Cancer Research volume 7, Article number: P1.12 (2005)
We have looked for genetic differences influencing cancer risk in the general human population. One human chromosomal region that recent data indicate as important for cancer risk is 19q13.2-3, more specifically a 69 kb region including the genes XPD, RAI, ASE1 and ERCC1. We and others have produced evidence of association between this region and occurrence of a variety of cancers, including basal cell carcinoma, melanoma, lung cancer, glioma, breast cancer, bladder cancer, and possibly head and neck cancer (see for instance ). A recent search along the region for markers with maximal association to basal cell carcinoma has led to a focus on the gene RAI . Moreover, the effect appears to be strongest among fairly young persons (<56 years of age).
These studies mainly involved analysis of single nucleotide polymorphisms in unrelated cases and controls. However, other studies have mapped a glioma tumor suppressor function to an almost overlapping region using deletions in tumor DNA . Finally, a recent genome-wide scan for chromosomal regions associated with aggressive prostate cancer located the strongest effector in a 6 Mb region, which includes the four genes mentioned .
It appears that this region of chromosome 19, most probably the gene RAI, often contains a genetic variant, which increases the risk of several cancers among fairly young humans. RAI produces an inhibitor of NF-κ B, and may thus be involved in apoptosis, which makes it very easy to rationalize its importance for cancer. In addition, studies of lung cancer have produced evidence for an independent effector within the 69 kb region of interest, possibly related to DNA repair.
Nexø BA, Vogel U, Olsen A, Ketelsen T, Bukowy Z, Thomsen BL, Wallin H, Overvad K, Tjønneland A: A specific haplotype of single nucleotide polymorphisms on chromosome 19q13.2-3 encompassing the genes RAI is indicative of postmenopausal breast cancer before age 55. Carcinogenesis. 2003, 24: 899-904. 10.1093/carcin/bgg043.
Rockenbauer E, Bendixen MH, Bukowy Z, Yin J, Jacobsen NR, Hedayati MA, Vogel U, Grossman L, Bolund L, Nexø BA: Association of chromosome 19q13.2-3 with basal cell carcinoma: tentative delineation of an involved region using data for single nucleotide polymorphisms in two cohorts. Carcinogenesis. 2002, 23: 1149-1153. 10.1093/carcin/23.7.1149.
Hartmann C, Johnk L, Kitange G, Wu Y, Ashworth LK, Jenkins RB, Louis DN: Transcript map of the 23.7 Mb D19S112-D19S246 candidate tumor suppressor region on the long arm of chromosome 19. Cancer Res. 2002, 62: 4100-4108.
Slager SL, Schaid DJ, Cunningham JM, McDonnell SK, Marks AF, Peterson BJ, Hebbring SJ, Anderson S, French AJ, Thibodeau SN: Confirmation of linkage of prostate cancer aggressiveness with chromosome 19q. Am J Hum Genet. 2003, 72: 759-762. 10.1086/368230.
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Nexø, B., Vogel, U., Overvad, K. et al. Who gets cancer?. Breast Cancer Res 7, P1.12 (2005) doi:10.1186/bcr1099
- Prostate Cancer
- Cancer Risk
- Basal Cell Carcinoma
- Tumor Suppressor Function