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LINE1 methylation levels in pre-diagnostic leukocyte DNA and future renal cell carcinoma risk.

https://arctichealth.org/en/permalink/ahliterature268361
Source
Epigenetics. 2015;10(4):282-92
Publication Type
Article
Date
2015
Author
Sara Karami
Gabriella Andreotti
Linda M Liao
Ruth M Pfeiffer
Stephanie J Weinstein
Mark P Purdue
Jonathan N Hofmann
Demetrius Albanes
Satu Mannisto
Lee E Moore
Source
Epigenetics. 2015;10(4):282-92
Date
2015
Language
English
Publication Type
Article
Keywords
Aged
Carcinoma, Renal Cell - diagnosis - epidemiology - genetics
DNA Methylation
Female
Finland
Humans
Kidney Neoplasms - diagnosis - epidemiology - genetics
Leukocytes - metabolism - pathology
Long Interspersed Nucleotide Elements
Male
Middle Aged
Smoking
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.
PubMed ID
25647181 View in PubMed
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