Two variants on chromosome 17 confer prostate cancer risk, and the one in TCF2 protects against type 2 diabetes.
Gudmundsson J,
Sulem P,
Steinthorsdottir V,
Bergthorsson JT,
Thorleifsson G,
Manolescu A,
Rafnar T,
Gudbjartsson D,
Agnarsson BA,
Baker A,
Sigurdsson A,
Benediktsdottir KR,
Jakobsdottir M,
Blondal T,
Stacey SN,
Helgason A,
Gunnarsdottir S,
Olafsdottir A,
Kristinsson KT,
Birgisdottir B,
Ghosh S,
Thorlacius S,
Magnusdottir D,
Stefansdottir G,
Kristjansson K,
Bagger Y,
Wilensky RL,
Reilly MP,
Morris AD,
Kimber CH,
Adeyemo A,
Chen Y,
Zhou J,
So WY,
Tong PC,
Ng MC,
Hansen T,
Andersen G,
Borch-Johnsen K,
Jorgensen T,
Tres A,
Fuertes F,
Ruiz-Echarri M,
Asin L,
Saez B,
van Boven E,
Klaver S,
Swinkels DW,
Aben KK,
Graif T,
Cashy J,
Suarez BK,
van Vierssen Trip O,
Frigge ML,
Ober C,
Hofker MH,
Wijmenga C,
Christiansen C,
Rader DJ,
Palmer CN,
Rotimi C,
Chan JC,
Pedersen O,
Sigurdsson G,
Benediktsson R,
Jonsson E,
Einarsson GV,
Mayordomo JI,
Catalona WJ,
Kiemeney LA,
Barkardottir RB,
Gulcher JR,
Thorsteinsdottir U,
Kong A,
Stefansson K.
deCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. julius.gudmundsson@decode.is
We performed a genome-wide association scan to search for sequence variants conferring risk of prostate cancer using 1,501 Icelandic men with prostate cancer and 11,290 controls. Follow-up studies involving three additional case-control groups replicated an association of two variants on chromosome 17 with the disease. These two variants, 33 Mb apart, fall within a region previously implicated by family-based linkage studies on prostate cancer. The risks conferred by these variants are moderate individually (allele odds ratio of about 1.20), but because they are common, their joint population attributable risk is substantial. One of the variants is in TCF2 (HNF1beta), a gene known to be mutated in individuals with maturity-onset diabetes of the young type 5. Results from eight case-control groups, including one West African and one Chinese, demonstrate that this variant confers protection against type 2 diabetes.
PMID: 17603485 [PubMed - indexed for MEDLINE]