Concerning the cancer cases in the EPIC-Italy we performed 2 sensitivity analyses: i) when excluding the subjects that developed cancer later in life, all identified CpG sites remained nominally significant (p < 0.05), 12 being Bonferroni significant (p < 0.05/14 = 3.75e − 03) except for cg22856765 (p = 0.0575) (Table A.13); ii) when not correcting for cancer case status, all associations remained significant (p < 3.75e − 06) (Table A.14). 3.3.
For the available back-extrapolated data, we found a significant or borderline significance global hypomethylation on somatic chromosomes in relation to exposure to NO 2 and NO x in both countries and with the two back-extrapolation methods (Supplemental Table A.3 and A.4).
The association with NO x did not reach statistical significance in EPIC-NL, which could be attributed to a lower statistical power, to the overall lower exposure levels observed in the Netherlands, or to other population differences between the 2 cohorts.