TY - JOUR
T1 - Opposite association of two PPARG variants with cancer: over-representation of H449H in endometrial carcinoma cases and under-representation of P12A in renal cell carcinoma cases
AU - Smith, WM
AU - Zhou, X-P
AU - Kurose, K
AU - Gao, X
AU - Latif, Farida
AU - Kroll, T
AU - Sugano, K
AU - Cannistra, SA
AU - Clinton, SK
AU - Maher, Eamonn
AU - Prior, TW
AU - Eng, C
PY - 2001/8/1
Y1 - 2001/8/1
N2 - Peroxisome proliferator activated receptor gamma (PPAR gamma) is a nuclear hormone receptor that has been shown to regulate differentiation and cell growth. Studies of the differentiative effects of PPAR gamma agonists on several cancer cell lines led to the hypothesis that dysfunction of PPAR gamma contributes to tumorigenesis. These functional observations were strengthened by genetic evidence: somatic loss-of-function mutations in PPARG, encoding PPAR gamma, in sporadic colorectal carcinomas and somatic translocation of PAX8 and PPARG in follicular thyroid carcinoma. Recently overrepresentation of the H449H variant was found in a cohort of American patients with glioblastoma multiforme. The glioblastoma multiforme data suggest that PPARG contributes common, low-penetrance alleles for cancer susceptibility. To test this hypothesis in a broader range of cancers we examined a series of carcinomas of the cervix, endometrium, ovary, prostate, and kidney for germline sequence variation in PPARG. In addition to the two common sequence variants, P12A and H449H, there were five other sequence variants. P12A alleles were underrepresented in renal cell carcinoma patients compared to country-of-origin race-matched controls (3.75% vs. 12.1%, P
AB - Peroxisome proliferator activated receptor gamma (PPAR gamma) is a nuclear hormone receptor that has been shown to regulate differentiation and cell growth. Studies of the differentiative effects of PPAR gamma agonists on several cancer cell lines led to the hypothesis that dysfunction of PPAR gamma contributes to tumorigenesis. These functional observations were strengthened by genetic evidence: somatic loss-of-function mutations in PPARG, encoding PPAR gamma, in sporadic colorectal carcinomas and somatic translocation of PAX8 and PPARG in follicular thyroid carcinoma. Recently overrepresentation of the H449H variant was found in a cohort of American patients with glioblastoma multiforme. The glioblastoma multiforme data suggest that PPARG contributes common, low-penetrance alleles for cancer susceptibility. To test this hypothesis in a broader range of cancers we examined a series of carcinomas of the cervix, endometrium, ovary, prostate, and kidney for germline sequence variation in PPARG. In addition to the two common sequence variants, P12A and H449H, there were five other sequence variants. P12A alleles were underrepresented in renal cell carcinoma patients compared to country-of-origin race-matched controls (3.75% vs. 12.1%, P
UR - http://www.scopus.com/inward/record.url?scp=17944367989&partnerID=8YFLogxK
U2 - 10.1007/s004390100563
DO - 10.1007/s004390100563
M3 - Article
C2 - 11511919
SN - 1432-1203
SN - 1432-1203
SN - 1432-1203
VL - 109
SP - 146
EP - 151
JO - Human Genetics
JF - Human Genetics
IS - 2
ER -
