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Int J Mol Epidemiol Genet 2011;2(2):185-195
Original Article
Design and validity of a clinic-based case-control study on the molecular
epidemiology of lymphoma
Prema Peethambaram, Brooke L. Fridley, Robert A. Vierkant, Melissa C. Larson, Kimberly R. Kalli, Elaine A. Elliott, Ann L.
Oberg, Kristin L. White, David N. Rider, Gary L. Keeney, Julie M. Cunningham, Lynn C. Hartmann, Ellen L. Goode
Departments of 1Oncology, Health Sciences Research, and Laboratory Medicine and Pathology, Mayo Clinic College of
Medicine, Rochester, MN, USA
Received March 11, 2011; accepted April 22, 2011; Epub May 2, 2011; published May 15, 2011
Abstract: Using the most comprehensive approach to selecting polymorphisms to date, we sought to examine whether time to
recurrence in ovarian cancer was associated with common inherited variation in eight genes involved in drug metabolism,
multi-drug resistance, or DNA repair, namely ABCB1, CYP2C8, CYP3A4, ERCC1, ERCC2, GSTM1, XPC, and XRCC1. Invasive
epithelial ovarian cancer patients (N=445) seen at Mayo Clinic from 1999 to 2009 with 275 observed recurrences or deaths
were analyzed at 94 SNPs in these candidate genes. Cox regression was used to estimate hazard ratios and 95% confidence
intervals for each single nucleotide polymorphism (SNP) and outcome (defined as time to recurrence or death, whichever
came first). Analyses were conducted at the gene level and on case subsets defined by histopathology and chemotherapeutic
agent. At ABCB1, minor alleles at several SNPs were associated with outcome, with the most significant being the intronic
SNP rs12334183 (HR=0.65, 95% CI 0.51-0.83; p=0.0005). Overall variation in ABCB1 was predictive of outcome as well
(p=0.003). At ERCC2, minor alleles at several SNPs were associated with outcome among women with high-grade serous
disease (e.g., rs238417, HR 0.74, 95% CI 0.59-0.92; p=0.006). No associations with outcome were observed in GSTM1,
CYP2C8, CYP3A4, ERCC1, XPC, or XRCC1. Inherited variation in ABCB1 and ERCC2 was associated with outcome in
patients with ovarian cancer seen at Mayo. As the associated SNPs have not been studied previously in ovarian cancer, these
findings suggest novel sites of variation which may, in part, explain the range of treatment responses seen in this disease.
(IJMEG1103003).
Keywords: Ovarian cancer, drug-related variants, metabolism
Full Text PDF
Address all correspondence to:
Ellen L. Goode, PhD
Department of Health Sciences Research
Mayo Clinic College of Medicine
200 First Street SW
Rochester, MN 55905, USA
Tel: 507/266-7997
Fax: 507/266-2478
E-mail: egoode@mayo.edu
Original Article
Design and validity of a clinic-based case-control study on the molecular
epidemiology of lymphoma
Prema Peethambaram, Brooke L. Fridley, Robert A. Vierkant, Melissa C. Larson, Kimberly R. Kalli, Elaine A. Elliott, Ann L.
Oberg, Kristin L. White, David N. Rider, Gary L. Keeney, Julie M. Cunningham, Lynn C. Hartmann, Ellen L. Goode
Departments of 1Oncology, Health Sciences Research, and Laboratory Medicine and Pathology, Mayo Clinic College of
Medicine, Rochester, MN, USA
Received March 11, 2011; accepted April 22, 2011; Epub May 2, 2011; published May 15, 2011
Abstract: Using the most comprehensive approach to selecting polymorphisms to date, we sought to examine whether time to
recurrence in ovarian cancer was associated with common inherited variation in eight genes involved in drug metabolism,
multi-drug resistance, or DNA repair, namely ABCB1, CYP2C8, CYP3A4, ERCC1, ERCC2, GSTM1, XPC, and XRCC1. Invasive
epithelial ovarian cancer patients (N=445) seen at Mayo Clinic from 1999 to 2009 with 275 observed recurrences or deaths
were analyzed at 94 SNPs in these candidate genes. Cox regression was used to estimate hazard ratios and 95% confidence
intervals for each single nucleotide polymorphism (SNP) and outcome (defined as time to recurrence or death, whichever
came first). Analyses were conducted at the gene level and on case subsets defined by histopathology and chemotherapeutic
agent. At ABCB1, minor alleles at several SNPs were associated with outcome, with the most significant being the intronic
SNP rs12334183 (HR=0.65, 95% CI 0.51-0.83; p=0.0005). Overall variation in ABCB1 was predictive of outcome as well
(p=0.003). At ERCC2, minor alleles at several SNPs were associated with outcome among women with high-grade serous
disease (e.g., rs238417, HR 0.74, 95% CI 0.59-0.92; p=0.006). No associations with outcome were observed in GSTM1,
CYP2C8, CYP3A4, ERCC1, XPC, or XRCC1. Inherited variation in ABCB1 and ERCC2 was associated with outcome in
patients with ovarian cancer seen at Mayo. As the associated SNPs have not been studied previously in ovarian cancer, these
findings suggest novel sites of variation which may, in part, explain the range of treatment responses seen in this disease.
(IJMEG1103003).
Keywords: Ovarian cancer, drug-related variants, metabolism
Full Text PDF
Address all correspondence to:
Ellen L. Goode, PhD
Department of Health Sciences Research
Mayo Clinic College of Medicine
200 First Street SW
Rochester, MN 55905, USA
Tel: 507/266-7997
Fax: 507/266-2478
E-mail: egoode@mayo.edu
