Skip to Main Content

An official website of the United States government

Government Funding Lapse

Because of a lapse in government funding, the information on this website may not be up to date, transactions submitted via the website may not be processed, and the agency may not be able to respond to inquiries until appropriations are enacted. The NIH Clinical Center (the research hospital of NIH) is open. For more details about its operating status, please visit  cc.nih.gov. Updates regarding government operating status and resumption of normal operations can be found at OPM.gov.

About this Publication
Title
LINE1 methylation levels in pre-diagnostic leukocyte DNA and future renal cell carcinoma risk.
Pubmed ID
25647181 (View this publication on the PubMed website)
Publication
Epigenetics. 2015; Volume 10 (Issue 4): Pages 282-92
Authors
Karami S, Andreotti G, Liao LM, Pfeiffer RM, Weinstein SJ, Purdue MP, Hofmann JN, Albanes D, Mannisto S, Moore LE
Affiliations
  • a Division of Cancer Epidemiology and Genetics (DCEG); US National Cancer Institute (NCI); National Institutes of Health (NIH); Department of Health and Human Services (DHHS) ; Rockville , MD USA.
Abstract

Higher levels of LINE1 methylation in blood DNA have been associated with increased kidney cancer risk using post-diagnostically collected samples; however, this association has never been examined using pre-diagnostic samples. We examined the association between LINE1 %5mC and renal cell carcinoma (RCC) risk using pre-diagnostic blood DNA from the United States-based, Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO) (215 cases/436 controls), and the Alpha-tocopherol, Beta-carotene Cancer Prevention Study (ATBC) of Finnish male smokers (191 cases/575 controls). Logistic regression adjusted for age at blood draw, study center, pack-years of smoking, body mass index, hypertension, dietary alcohol intake, family history of cancer, and sex was used to calculate odds ratios (ORs) and 95% confidence intervals (CIs) using cohort and sex-specific methylation categories. In PLCO, higher, although non-significant, RCC risk was observed for participants at or above median methylation level (M2) compared to those below the median (M1) (OR: 1.37, 95% CI: 0.96-1.95). The association was stronger in males (M2 vs. M1, OR: 1.54, 95% CI: 1.00-2.39) and statistically significant among male smokers (M2 vs. M1, OR: 2.60, 95% CI: 1.46-4.63). A significant interaction for smoking was also detected (P-interaction: 0.01). No association was found among females or female smokers. Findings for male smokers were replicated in ATBC (M2 vs. M1, OR: 1.31, 95% CI: 1.07-1.60). In a pooled analysis of PLCO and ATBC male smokers (281 cases/755 controls), the OR among subjects at or above median methylation level (M2) compared to those below the median (M1) was 1.89 (95% CI: 1.34-2.67, P-value: 3 x 10(-4)); a trend was also observed by methylation quartile (P-trend: 0.002). These findings suggest that higher LINE1 methylation levels measured prior to cancer diagnosis may be a biomarker of future RCC risk among male smokers.

Related CDAS Studies
Related CDAS Projects