title: Caspase polymorphisms and genetic susceptibility to multiple myeloma.
abstract: 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 (OR(AG) = 0.8, 95% CI = 0.5-1.3; OR(AA) = 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.
authors.affiliation: Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892-7240, USA. hosgoodd@mail.nih.gov
authors.forename: H Dean
authors.initials: HD
authors.lastname: Hosgood
authors.forename: Dalsu
authors.initials: D
authors.lastname: Baris
authors.forename: Yawei
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhu
authors.forename: Tongzhang
authors.initials: T
authors.lastname: Zheng
authors.forename: Meredith
authors.initials: M
authors.lastname: Yeager
authors.forename: Robert
authors.initials: R
authors.lastname: Welch
authors.forename: Shelia
authors.initials: S
authors.lastname: Zahm
authors.forename: Stephen
authors.initials: S
authors.lastname: Chanock
authors.forename: Nathaniel
authors.initials: N
authors.lastname: Rothman
authors.forename: Qing
authors.initials: Q
authors.lastname: Lan
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D053455:Caspase 10 / Q000235:genetics*; D053148:Caspase 3 / Q000235:genetics*; D053181:Caspase 8 / Q000235:genetics*; D053453:Caspase 9 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000209:etiology / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide
chemical_list: D053455:Caspase 10; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9