Selected polymorphisms in sex hormone-related genes, circulating sex hormones and risk of endometrial cancer.
BACKGROUND
The role of estrogen and progesterone in the development of endometrial cancer is well documented. Few studies have examined the association of genetic variants in sex hormone-related genes with endometrial cancer risk.


METHODS
We conducted a case-control study nested within three cohorts to examine the association of endometrial cancer risk with polymorphisms in hormone-related genes among 391 cases (92% postmenopausal at diagnosis) and 712 individually-matched controls. We also examined the association of these polymorphisms with circulating levels of sex hormones and SHBG in a cross-sectional analysis including 596 healthy postmenopausal women at blood donation (controls from this nested case-control study and from a nested case-control study of breast cancer in one of the three cohorts).


RESULTS
Adjusting for endometrial cancer risk factors, the A allele of rs4775936 in CYP19 was significantly associated (OR(per allele)=1.22, 95% CI=1.01-1.47, p(trend)=0.04), while the T allele of rs10046 was marginally associated with increased risk of endometrial cancer (OR(per allele)=1.20, 95% CI=0.99-1.45, p(trend)=0.06). PGR rs1042838 was also marginally associated with risk (OR(per allele)=1.25, 95% CI=0.96-1.61, p(trend)=0.09). No significant association was found for the other polymorphisms, i.e. CYP1B1 rs1800440 and rs1056836, UGT1A1 rs8175347, SHBG rs6259 and ESR1 rs2234693. Rs8175347 was significantly associated with postmenopausal levels of estradiol, free estradiol and estrone and rs6259 with SHBG and estradiol.


CONCLUSIONS
Our findings support an association between genetic variants in CYP19, and possibly PGR, and risk of endometrial cancer.
Department of Medical Biosciences, Pathology, Umeå University, Umeå, Sweden.
Eva
E
Lundin
Isaac
I
Wirgin
Annekatrin
A
Lukanova
Yelena
Y
Afanasyeva
Vittorio
V
Krogh
Tomas
T
Axelsson
Kari
K
Hemminki
Tess V
TV
Clendenen
Alan A
AA
Arslan
Nina
N
Ohlson
Sabina
S
Sieri
Nirmal
N
Roy
Karen L
KL
Koenig
Annika
A
Idahl
Franco
F
Berrino
Paolo
P
Toniolo
Göran
G
Hallmans
Asta
A
Försti
Paola
P
Muti
Per
P
Lenner
Roy E
RE
Shore
Anne
A
Zeleniuch-Jacquotte
D000368:Aged; D001141:Aromatase / Q000235:genetics*; D016022:Case-Control Studies; D003430:Cross-Sectional Studies; D016889:Endometrial Neoplasms / Q000097:blood* / Q000453:epidemiology / Q000235:genetics*; D005260:Female; D012739:Gonadal Steroid Hormones / Q000097:blood* / Q000235:genetics*; D006801:Humans; D007558:Italy / Q000453:epidemiology; D008875:Middle Aged; D009519:New York City / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D017698:Postmenopause / Q000235:genetics; D011980:Receptors, Progesterone / Q000235:genetics*; D012738:Sex Hormone-Binding Globulin / Q000235:genetics; D013548:Sweden / Q000453:epidemiology
D012739:Gonadal Steroid Hormones; D011980:Receptors, Progesterone; D012738:Sex Hormone-Binding Globulin; D001141:Aromatase