TY - JOUR
T1 - Caspase polymorphisms and genetic susceptibility to multiple myeloma
AU - Hosgood, H. Dean
AU - Baris, Dalsu
AU - Zhang, Yawei
AU - Zhu, Yong
AU - Zheng, Tongzhang
AU - Yeager, Meredith
AU - Welch, Robert
AU - Zahm, Shelia
AU - Chanock, Stephen
AU - Rothman, Nathaniel
AU - Lan, Qing
PY - 2008
Y1 - 2008
N2 - Multiple myeloma is a haematological malignency, characterized by clonal expansion of plasma cells. However, little is known about the cause of multiple myeloma. Cancer cells must avoid apoptosis to ensure unregulated tumour formation and growth. The highly conserved caspase cascade is essential to the regulation of the apoptotic pathway. To examine if five single nucleotide polymorphisms (SNPs) in four caspase genes [CASP3 Ex8-280 C > A (rs6948), CASP3 Ex8 + 567 T > C (rs1049216), CASP8 Ex14-271 A > T (rs13113), CASP9 Ex5 + 32 G > A (rs1052576), CASP10 Ex3-171 A > G (rs39001150)] alter multiple myeloma risk, we conducted a population-based case-control study of women (128 cases; 516 controls) in Connecticut. Compared to individuals with the TT genotype of CASP3 Ex8 + 567 T > C, subjects with the CC genotype had a five-fold decreased risk of multiple myeloma (odds ratio (OR)CC=0.2, 95% confidence interval (CI) - 0.0-1.0). Further, individuals with the AG and AA genotypes of CASP9 Ex5+32 G > A also experienced a decreased risk of multiple myeloma (ORAG=0.8, 95% CI - 0.5-1.3; ORAA=0.5, 95% CI - 0.3-0.9; p-trend = 0.02). While no previous study has evaluated the association between caspase genes and multiple myeloma, studies have found associations with lung, breast, esophageal, gastric, colorectal and cervical cancers. Our parallel study of non-Hodgkin lymphoma, which utilized the same controls, found strong evidence that caspase genes play a key role in lymphogenesis. The protective associations observed in two key caspase genes suggest that genetic variation in CASP genes may play an important role in the aetiology of multiple myeloma.
AB - Multiple myeloma is a haematological malignency, characterized by clonal expansion of plasma cells. However, little is known about the cause of multiple myeloma. Cancer cells must avoid apoptosis to ensure unregulated tumour formation and growth. The highly conserved caspase cascade is essential to the regulation of the apoptotic pathway. To examine if five single nucleotide polymorphisms (SNPs) in four caspase genes [CASP3 Ex8-280 C > A (rs6948), CASP3 Ex8 + 567 T > C (rs1049216), CASP8 Ex14-271 A > T (rs13113), CASP9 Ex5 + 32 G > A (rs1052576), CASP10 Ex3-171 A > G (rs39001150)] alter multiple myeloma risk, we conducted a population-based case-control study of women (128 cases; 516 controls) in Connecticut. Compared to individuals with the TT genotype of CASP3 Ex8 + 567 T > C, subjects with the CC genotype had a five-fold decreased risk of multiple myeloma (odds ratio (OR)CC=0.2, 95% confidence interval (CI) - 0.0-1.0). Further, individuals with the AG and AA genotypes of CASP9 Ex5+32 G > A also experienced a decreased risk of multiple myeloma (ORAG=0.8, 95% CI - 0.5-1.3; ORAA=0.5, 95% CI - 0.3-0.9; p-trend = 0.02). While no previous study has evaluated the association between caspase genes and multiple myeloma, studies have found associations with lung, breast, esophageal, gastric, colorectal and cervical cancers. Our parallel study of non-Hodgkin lymphoma, which utilized the same controls, found strong evidence that caspase genes play a key role in lymphogenesis. The protective associations observed in two key caspase genes suggest that genetic variation in CASP genes may play an important role in the aetiology of multiple myeloma.
KW - Caspase
KW - Multiple myeloma
KW - Polymorphism
KW - Risk factors
KW - Snp
KW - Variant
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U2 - 10.1002/hon.852
DO - 10.1002/hon.852
M3 - Article
C2 - 18381704
AN - SCOPUS:55249115329
SN - 0278-0232
VL - 26
SP - 148
EP - 151
JO - Hematological Oncology
JF - Hematological Oncology
IS - 3
ER -