Prospective analysis of DNA damage and repair markers of lung cancer risk from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial

Alice J. Sigurdson, Irene M. Jones, Qingyi Wei, Xifeng Wu, Margaret R. Spitz, Douglas A. Stram, Myron D. Gross, Wen Yi Huang, Li E. Wang, Jian Gu, Cynthia B. Thomas, Douglas J. Reding, Richard B. Hayes, Neil E. Caporaso

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Abstract

Mutagen challenge and DNA repair assays have been used in case-control studies for nearly three decades to assess human cancer risk. The findings still engender controversy because blood was drawn after cancer diagnosis so the results may be biased, a type called 'reverse causation'.We therefore used Epstein-Barr virus-transformed lymphoblastoid cell lines established from prospectively collected peripheral blood samples to evaluate lung cancer risk in relation to three DNA repair assays: alkaline Comet assay, host cell reactivation (HCR) assay with the mutagen benzo[a]pyrene diol epoxide and the bleomycin mutagen sensitivity assay. Cases (n 5 117) were diagnosed with lung cancer between 0.3 and 6 years after blood collection and controls (n 5 117) were frequency matched on calendar year and age at blood collection, gender and smoking history; all races were included. Case and control status was unknown to laboratory investigators. In unconditional logistic regression analyses, statistically significantly increased lung cancer odds ratios (ORadjusted) were observed for bleomycin mutagen sensitivity as quartiles of chromatid breaks/ cell [relative to the lowest quartile, OR = 1.2, 95% confidence interval (CI): 0.5-2.5; OR = 1.4, 95% CI: 0.7-3.1; OR = 2.1, 95% CI: 1.0-4.4, respectively, Ptrend = 0.04]. The magnitude of the association between the bleomycin assay and lung cancer risk was modest compared with those reported in previous lung cancer studies but was strengthened when we included only incident cases diagnosed more than a year after blood collection (Ptrend = 0.02), supporting the notion the assay may be a measure of cancer susceptibility. The Comet and HCR assays were unrelated to lung cancer risk.

Original languageEnglish (US)
Pages (from-to)69-73
Number of pages5
JournalCarcinogenesis
Volume32
Issue number1
DOIs
StatePublished - Dec 1 2011

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Early Detection of Cancer
DNA Repair
Ovarian Neoplasms
DNA Damage
Colorectal Neoplasms
Lung Neoplasms
Prostatic Neoplasms
Mutagens
Bleomycin
Confidence Intervals
Neoplasms
Transformed Cell Line
Chromatids
Comet Assay
Benzo(a)pyrene
Epoxy Compounds
Human Herpesvirus 4
Causality
Case-Control Studies
Logistic Models

ASJC Scopus subject areas

  • Cancer Research

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Prospective analysis of DNA damage and repair markers of lung cancer risk from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. / Sigurdson, Alice J.; Jones, Irene M.; Wei, Qingyi; Wu, Xifeng; Spitz, Margaret R.; Stram, Douglas A.; Gross, Myron D.; Huang, Wen Yi; Wang, Li E.; Gu, Jian; Thomas, Cynthia B.; Reding, Douglas J.; Hayes, Richard B.; Caporaso, Neil E.

In: Carcinogenesis, Vol. 32, No. 1, 01.12.2011, p. 69-73.

Research output: Contribution to journalArticle

Sigurdson, AJ, Jones, IM, Wei, Q, Wu, X, Spitz, MR, Stram, DA, Gross, MD, Huang, WY, Wang, LE, Gu, J, Thomas, CB, Reding, DJ, Hayes, RB & Caporaso, NE 2011, 'Prospective analysis of DNA damage and repair markers of lung cancer risk from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial', Carcinogenesis, vol. 32, no. 1, pp. 69-73. https://doi.org/10.1093/carcin/bgq204
Sigurdson, Alice J. ; Jones, Irene M. ; Wei, Qingyi ; Wu, Xifeng ; Spitz, Margaret R. ; Stram, Douglas A. ; Gross, Myron D. ; Huang, Wen Yi ; Wang, Li E. ; Gu, Jian ; Thomas, Cynthia B. ; Reding, Douglas J. ; Hayes, Richard B. ; Caporaso, Neil E. / Prospective analysis of DNA damage and repair markers of lung cancer risk from the Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial. In: Carcinogenesis. 2011 ; Vol. 32, No. 1. pp. 69-73.
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