Genetic variation in cell cycle and apoptosis related genes and multiple myeloma risk

Hosgood, H. Dean; Baris, Dalsu; Zhang, Yawei; Berndt, Sonja I.; Menashe, Idan; Morton, Lindsay M.; Lee, Kyoung-Mu; Yeager, Meredith; Zahm, Shelia H.; Chanock, Stephen; Zheng, Tongzhang; Lan, Qing

doi:10.1016/j.leukres.2009.03.013

« Previous Next »Leukemia Research
Volume 33, Issue 12 , Pages 1609-1614, December 2009

Genetic variation in cell cycle and apoptosis related genes and multiple myeloma risk

H. Dean Hosgood III
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States
- Corresponding author at: National Cancer Institute, Division of Cancer Epidemiology and Genetics, Occupational and Environmental Epidemiology Branch, 6120 Executive Blvd., EPS 8118, MCS 7240, Bethesda, MD 20892-7240, United States. Tel.: +1 301 594 4649; fax: +1 301 402 1819.
Dalsu Baris
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States
Yawei Zhang
- Department of Epidemiology and Public Health, Yale School of Medicine, New Haven, CT, United States
Sonja I. Berndt
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States
Idan Menashe
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States
Lindsay M. Morton
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States
Kyoung-Mu Lee
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States
Meredith Yeager
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States
Shelia H. Zahm
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States
Stephen Chanock
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States
Tongzhang Zheng
- Department of Epidemiology and Public Health, Yale School of Medicine, New Haven, CT, United States
Qing Lan
- Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Department of Health and Human Services, Bethesda, MD, United States

Received 31 December 2008; received in revised form 11 March 2009; accepted 12 March 2009. published online 07 March 2011.

Abstract

Genetic variation may be an important risk factor for multiple myeloma. A hallmark of tumor formation and growth is cell cycle dysregulation and apoptosis avoidance. We previously reported the association of genetic variation in caspase genes, the apoptotic-regulating family, and multiple myeloma risk. To further examine if genetic variation in key cell cycle and apoptosis genes alters multiple myeloma risk, we genotyped 276 tag SNPs in 27 gene regions in a population-based case–control study of non-Hispanic Caucasian women (108 cases; 482 controls) in Connecticut. Logistic regression assessed the effect of each SNP on multiple myeloma risk and the minP test assessed the association at the gene region level. Three gene regions were significantly associated with risk of multiple myeloma (BAX minP=0.018, CASP9 minP=0.025, and RIPK1 minP=0.037). Further explorations identified the most significant variant of BAX, RIPK1, and CASP9 to be rs1042265, rs9391981, and rs751643, respectively. The A variant at rs1042265 (OR_GA+AA=0.40, 95% CI=0.21–0.78) and the C variant at rs9391981 (OR_GC+CC=0.32, 95% CI=0.12–0.81) were associated with a decreased risk of multiple myeloma. The G variant at rs7516435 was associated with an increased risk of multiple myeloma (OR_AG=1.48, 95% CI=0.94–2.32; OR_GG=2.59, 95% CI=1.30–5.15; p_trend=0.005). Haplotype analyses supported the SNP findings. These findings suggest that genetic variation in cell cycle and apoptosis genes may play a key role in multiple myeloma and warrant further investigation through replication studies.