Non-small cell lung carcinoma (NSCLC) accounts for about 85% of all lung cancers, with 2% of NSCLC cases under the age of 45. Previous studies have associated the INK4 locus, a gene cluster encoding three tumor suppressor proteins with lung and other cancers. One of the encoded transcripts, CDKN2A/p16, is associated with biological aging. INK4 locus expression was assessed by qRT-PCR in formalin-fixed lung tumor and non-malignant tissue. Non-malignant expression of p14, p15 and p16 RNA was similar to that of malignant (Mann-Whitney U = 511, p = 0.440). In tumor tissue, there was low ANRIL expression in both age groups (<50 n = 45, Mean Rank 36.89; >50 n = 33, Mean Rank 43.06; Mann-Whitney U = 625, p = 0.235). p14 was minimally expressed in non-malignant lung tissue and in both age groups, and only slightly higher in tumor tissue. p15 demonstrated a similar pattern, while p16 RNA was more highly expressed in the older group. This trend was reflected in protein expression. The relative levels of ANRIL expression were low and quite variable in malignant tissue, the median value being lower in non-malignant than in non-malignant tissue. SNP rs1063192 (C/T), located within the ANRIL transcript has been associated with age-related diseases and cancer including glioma and with modulation of ANRIL expression. Lack of the rs2811712 G allele was found with increased gene expression normalized to beta2 microglobulin (B2M) in p16 [p16/B2M% = 1.26 (A/AA) vs 0.45 (AG), n = 77] and p14 [p14/B2M% 0.0008 (A/AA) vs 0.008 (AG); n = 13 (p = 0.025)]. These data show measurable differences in INK4 gene expression in this patient group. The age-related INK4 locus may contribute to early onset of lung cancer in this patient group. Complex tumorigenic pathways in different histologies as well as in older vs younger tissues complicate clear designation of these effects.
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