TY - JOUR
T1 - Cytokine and cytokine receptor genes of the adaptive immune response are differentially associated with breast cancer risk in American women of African and European ancestry
AU - Quan, Lei
AU - Gong, Zhihong
AU - Yao, Song
AU - Bandera, Elisa V.
AU - Zirpoli, Gary
AU - Hwang, Helena
AU - Roberts, Michelle
AU - Ciupak, Gregory
AU - Davis, Warren
AU - Sucheston, Lara
AU - Pawlish, Karen
AU - Bovbjerg, Dana H.
AU - Jandorf, Lina
AU - Cabasag, Citadel
AU - Coignet, Jean Gabriel
AU - Ambrosone, Christine B.
AU - Hong, Chi Chen
PY - 2014/3/15
Y1 - 2014/3/15
N2 - Disparities in breast cancer biology are evident between American women of African ancestry (AA) and European ancestry (EA) and may be due, in part, to differences in immune function. To assess the potential role of constitutional host immunity on breast carcinogenesis, we tested associations between breast cancer risk and 47 single nucleotide polymorphisms (SNPs) in 26 cytokine-related genes of the adaptive immune system using 650 EA (n = 335 cases) and 864 AA (n = 458 cases) women from the Women's Circle of Health Study (WCHS). With additional participant accrual to the WCHS, promising SNPs from the initial analysis were evaluated in a larger sample size (1,307 EAs and 1,365 AAs). Multivariate logistic regression found SNPs in genes important for T helper type 1 (Th1) immunity (IFNGR2 rs1059293, IL15RA rs2296135, LTA rs1041981), Th2 immunity (IL4R rs1801275), and T regulatory cell-mediated immunosuppression (TGFB1 rs1800469) associated with breast cancer risk, mainly among AAs. The combined effect of these five SNPs was highly significant among AAs (P-trend = 0.0005). When stratified by estrogen receptor (ER) status, LTA rs1041981 was associated with ER-positive breast cancers among EAs and marginally among AAs. Only among AA women, IL15 rs10833 and IL15RA rs2296135 were associated with ER-positive tumors, and IL12RB1 rs375947, IL15 rs10833 and TGFB1 rs1800469 were associated with ER-negative tumors. Our study systematically identified genetic variants in the adaptive immune response pathway associated with breast cancer risk, which appears to differ by ancestry groups, menopausal status and ER status. What's new? African American women are affected by aggressive and early-onset breast cancers more often than American women of European descent, though the reasons for this are not fully understood. Here, single nucleotide polymorphisms (SNPs) in genes involved in Th1 and Th2 immunity and in T regulatory cell-mediated immunosuppression were linked to breast cancer risk in African American women. Stratification according to estrogen-receptor status (ER positive or ER negative) revealed sets of risk-associated SNPs exclusive to African Americans. The findings suggest that host adaptive immunity plays a more prominent role in breast carcinogenesis among African Americans compared with European Americans.
AB - Disparities in breast cancer biology are evident between American women of African ancestry (AA) and European ancestry (EA) and may be due, in part, to differences in immune function. To assess the potential role of constitutional host immunity on breast carcinogenesis, we tested associations between breast cancer risk and 47 single nucleotide polymorphisms (SNPs) in 26 cytokine-related genes of the adaptive immune system using 650 EA (n = 335 cases) and 864 AA (n = 458 cases) women from the Women's Circle of Health Study (WCHS). With additional participant accrual to the WCHS, promising SNPs from the initial analysis were evaluated in a larger sample size (1,307 EAs and 1,365 AAs). Multivariate logistic regression found SNPs in genes important for T helper type 1 (Th1) immunity (IFNGR2 rs1059293, IL15RA rs2296135, LTA rs1041981), Th2 immunity (IL4R rs1801275), and T regulatory cell-mediated immunosuppression (TGFB1 rs1800469) associated with breast cancer risk, mainly among AAs. The combined effect of these five SNPs was highly significant among AAs (P-trend = 0.0005). When stratified by estrogen receptor (ER) status, LTA rs1041981 was associated with ER-positive breast cancers among EAs and marginally among AAs. Only among AA women, IL15 rs10833 and IL15RA rs2296135 were associated with ER-positive tumors, and IL12RB1 rs375947, IL15 rs10833 and TGFB1 rs1800469 were associated with ER-negative tumors. Our study systematically identified genetic variants in the adaptive immune response pathway associated with breast cancer risk, which appears to differ by ancestry groups, menopausal status and ER status. What's new? African American women are affected by aggressive and early-onset breast cancers more often than American women of European descent, though the reasons for this are not fully understood. Here, single nucleotide polymorphisms (SNPs) in genes involved in Th1 and Th2 immunity and in T regulatory cell-mediated immunosuppression were linked to breast cancer risk in African American women. Stratification according to estrogen-receptor status (ER positive or ER negative) revealed sets of risk-associated SNPs exclusive to African Americans. The findings suggest that host adaptive immunity plays a more prominent role in breast carcinogenesis among African Americans compared with European Americans.
KW - African-American
KW - adaptive immune response
KW - breast cancer
KW - cytokine
KW - disparity
KW - estrogen receptor
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U2 - 10.1002/ijc.28458
DO - 10.1002/ijc.28458
M3 - Article
C2 - 23996684
AN - SCOPUS:84891834160
SN - 0020-7136
VL - 134
SP - 1408
EP - 1421
JO - International Journal of Cancer
JF - International Journal of Cancer
IS - 6
ER -