title: LINE1 methylation levels in pre-diagnostic leukocyte DNA and future renal cell carcinoma risk.
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.
authors: 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.
authors: Sara
authors: S
authors: Karami
authors: Gabriella
authors: G
authors: Andreotti
authors: Linda M
authors: LM
authors: Liao
authors: Ruth M
authors: RM
authors: Pfeiffer
authors: Stephanie J
authors: SJ
authors: Weinstein
authors: Mark P
authors: MP
authors: Purdue
authors: Jonathan N
authors: JN
authors: Hofmann
authors: Demetrius
authors: D
authors: Albanes
authors: Satu
authors: S
authors: Mannisto
authors: Lee E
authors: LE
authors: Moore
mesh_terms: D000368:Aged; D002292:Carcinoma, Renal Cell / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D019175:DNA Methylation; D005260:Female; D005387:Finland; D006801:Humans; D007680:Kidney Neoplasms / Q000175:diagnosis* / Q000453:epidemiology / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology*; D020084:Long Interspersed Nucleotide Elements; D008297:Male; D008875:Middle Aged; D012907:Smoking
keywords: ATBC, cohort; PLCO; global methylation; nested case-contro; pre-diagnostic blood DNA; renal cell carcinoma; smoking interaction
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