CASP8 polymorphisms, estrogen and progesterone receptor status, and breast cancer risk.
OBJECTIVE
This study was conducted to evaluate the potential role of CASP8 genetic polymorphisms in the etiology of breast cancer in a case-control study, Korea.


METHODS
Incident breast cancer cases confirmed histologically (n = 1,599) were recruited from two hospitals in Seoul during 2001-2005. Control subjects (n = 1,536) were selected from the Health Examinee Cohort from Seoul and Gyeonggi Province surrounding Seoul, Korea. Three SNPs (D302H D > H, 5'-UTR C > T, and K337K G > A) were genotyped by the primer extension assay. The CASP8 D302H, which was not polymorphic in 48 samples, was excluded in further genotyping. Odds ratios and 95% confidential intervals (95% CIs) were estimated by unconditional logistic regression model adjusted for age at enrollment, education, age at first full-term pregnancy, cigarette smoking, and family history of breast cancer.


RESULTS
The 5'-UTR T allele containing genotypes (CT/TT) were associated with an increased risk of breast cancer, compared with those with the CC genotype (OR = 1.13, 95% CI = 0.95-1.34; and OR = 1.48, 95% CI = 1.04-2.10, respectively; P-trend = 0.02). When stratified by the estrogen and progesterone receptor status, the association between the 5'-UTR T allele and breast cancer risk was prominent in ER(+) and PR(+) cases among pre-menopausal women (OR = 1.31, 95% CI = 1.00-1.72 and OR = 1.40, 95% CI = 1.06-1.85, respectively), whereas the association was found prominent in ER(-) or PR(-) cases (OR = 1.32, 95% CI = 0.93-1.87 and OR = 1.42, 95% CI = 1.04-1.94, respectively) among post-menopausal women.


CONCLUSIONS
Our results thus suggest that the CASP8 5'-UTR C > T are associated with breast cancer risks and the effect may be modified by estrogen and progesterone receptor status.
Han
Sohee
S
Department of Preventive Medicine, Seoul National University College of Medicine, Chongno-Gu, Seoul, Korea.
Lee
Kyoung-Mu
KM
Choi
Ji-Yeob
JY
Park
Sue Kyung
SK
Lee
Ji-Young
JY
Lee
Jong Eun
JE
Noh
Dong-Young
DY
Ahn
Sei-Hyun
SH
Han
Wonshik
W
Kim
Dong-Hyun
DH
Hong
Yun-Chul
YC
Ha
Eunhee
E
Yoo
Keun-Young
KY
Kang
Daehee
D
D020121:5' Untranslated Regions; D000328:Adult; D001943:Breast Neoplasms / Q000208:ethnology / Q000235:genetics* / Q000378:metabolism; D016022:Case-Control Studies; D053181:Caspase 8 / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007723:Korea; D008875:Middle Aged; D016017:Odds Ratio; D011110:Polymorphism, Genetic; D011960:Receptors, Estrogen / Q000378:metabolism*; D011980:Receptors, Progesterone / Q000378:metabolism*; D012306:Risk
D020121:5' Untranslated Regions; D011960:Receptors, Estrogen; D011980:Receptors, Progesterone; D053181:Caspase 8