INT94774

Context Info Confidence 0.60 First Reported 2001 Last Reported 2011 Negated 7 Speculated 9 Reported most in Body Documents 43 Total Number 52 Disease Relevance 44.41 Pain Relevance 13.99

nucleoplasm (CDKN2A) DNA binding (CDKN2A) protein complex (CDKN2A) cytoplasm (CDKN2A) cytosol (CDKN2A) nucleolus (CDKN2A)

Anatomy Link Frequency podocytes 2 melanocyte 1 duct 1 CDKN2A (Homo sapiens)

Pain Link Frequency Relevance Heat aspirin 65 99.82 melanocortin 1 receptor 3323 99.46 Chronic pancreatitis 13 98.42 imagery 51 78.84 cINOD 248 53.36 Inflammation 59 45.12 addiction 22 5.00 palliative 18 5.00 cytokine 12 5.00 Inflammatory mediators 6 5.00

Disease Link Frequency Relevance Heat Cancer 1403 100.00 Acute Renal Failure 166 100.00 Burns 295 99.98 Skin Cancer 335 99.90 Metastasis 237 99.88 Pancreatic Ductal Carcinoma 8 99.84 Aneuploidy 76 99.82 Stomach Cancer 432 99.70 Melanoma 3263 99.56 Tetraploidy 54 99.52

Sentences Mentioned In

Key:

Protein

Mutation

Event

Anatomy

Negation

Speculation

Pain term

Disease term

The finding was associated to increased levels of some CDKIs, namely p27(Kip1) and p21(Cip1), whereas ASA did not affected p16(Ink4A) level at any of the concentrations employed.

Neg (not) Regulation (affected) of p16 associated with aspirin

1) Confidence 0.60 Published 2008 Journal Int J Immunopathol Pharmacol Section Abstract Doc Link 19144277 Disease Relevance 0.13 Pain Relevance 0.50

The finding was associated to increased levels of some CDKIs, namely p27(Kip1) and p21(Cip1), whereas ASA did not affected p16(Ink4A) level at any of the concentrations employed.

Neg (not) Regulation (affected) of Ink4A associated with aspirin

2) Confidence 0.60 Published 2008 Journal Int J Immunopathol Pharmacol Section Abstract Doc Link 19144277 Disease Relevance 0.13 Pain Relevance 0.50

We also explored whether the association of MC1R variants with melanoma risk differed if the CDKN2A mutations affected p16INK4a alone or both p16INK4 and p14ARF proteins.

Spec (whether) Regulation (affected) of p16INK4a associated with melanocortin 1 receptor and melanoma

3) Confidence 0.60 Published 2010 Journal JNCI Journal of the National Cancer Institute Section Body Doc Link PMC2957428 Disease Relevance 0.74 Pain Relevance 0.39

For each baseline endoscopy, samples were characterized for 17p LOH spanning TP53, TP53 mutations, DNA content abnormalities including tetraploidy and aneuploidy, 9p LOH spanning the CDKN2A (p16) locus, CDKN2A promoter methylation, and CDKN2A mutation in one biopsy every 2 cm in the Barrett's segment (average = 3.2, range 1–11 biopsies analyzed per study participant).

Regulation (spanning) of p16 associated with aneuploidy, tetraploidy and congenital anomalies

4) Confidence 0.45 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1808095 Disease Relevance 0.62 Pain Relevance 0

For each baseline endoscopy, samples were characterized for 17p LOH spanning TP53, TP53 mutations, DNA content abnormalities including tetraploidy and aneuploidy, 9p LOH spanning the CDKN2A (p16) locus, CDKN2A promoter methylation, and CDKN2A mutation in one biopsy every 2 cm in the Barrett's segment (average = 3.2, range 1–11 biopsies analyzed per study participant).

Regulation (spanning) of CDKN2A associated with aneuploidy, tetraploidy and congenital anomalies

5) Confidence 0.45 Published 2007 Journal PLoS Medicine Section Body Doc Link PMC1808095 Disease Relevance 0.62 Pain Relevance 0

and 2, thus affecting p16INK4a protein alone or both p16INK4a and p14ARF proteins (7).

Regulation (affecting) of p14ARF

6) Confidence 0.44 Published 2010 Journal JNCI Journal of the National Cancer Institute Section Body Doc Link PMC2957428 Disease Relevance 1.24 Pain Relevance 0.11

Moreover, it is not known whether the associations of MC1R variants with melanoma risk in CDKN2A carriers vary, depending on whether the CDKN2A mutation alters p16INK4A protein alone or both p16INK4A and p14ARF proteins.

Spec (whether) Regulation (alters) of p14ARF associated with melanocortin 1 receptor and melanoma

7) Confidence 0.44 Published 2010 Journal JNCI Journal of the National Cancer Institute Section Body Doc Link PMC2957428 Disease Relevance 1.20 Pain Relevance 0.84

We also investigated whether the associations of the frequent MC1R variants and number of MC1R variants with melanoma risk differed according to the type of CDKN2A mutations (mutations affecting p16INK4a protein only vs mutations affecting both p16INK4a and p14ARF proteins).

Regulation (affecting) of p14ARF associated with melanocortin 1 receptor and melanoma

8) Confidence 0.44 Published 2010 Journal JNCI Journal of the National Cancer Institute Section Body Doc Link PMC2957428 Disease Relevance 0.43 Pain Relevance 1.16

We also explored whether the association of MC1R variants with melanoma risk differed if the CDKN2A mutations affected p16INK4a alone or both p16INK4 and p14ARF proteins.

Spec (whether) Regulation (affected) of p14ARF associated with melanocortin 1 receptor and melanoma

9) Confidence 0.44 Published 2010 Journal JNCI Journal of the National Cancer Institute Section Body Doc Link PMC2957428 Disease Relevance 0.74 Pain Relevance 0.39

The median ages at examination among affected and unaffected CDKN2A mutation carriers were 47 and 41 years, respectively, in Europe; 42 and 34 years, respectively, in North America; and 54 and 47 years, respectively, in Australia.

Neg (unaffected) Regulation (unaffected) of CDKN2A

10) Confidence 0.44 Published 2010 Journal JNCI Journal of the National Cancer Institute Section Body Doc Link PMC2957428 Disease Relevance 0.61 Pain Relevance 0.51

A total of 23 nonsynonymous MC1R variants were detected in affected and unaffected CDKN2A mutation carriers of the 186 melanoma-prone families, and four of these variants (V60L, V92M, R151C, and R160W) showed a frequency more than 5% in these mutation carriers across all continents.

Neg (unaffected) Regulation (unaffected) of CDKN2A associated with melanocortin 1 receptor and melanoma

11) Confidence 0.44 Published 2010 Journal JNCI Journal of the National Cancer Institute Section Body Doc Link PMC2957428 Disease Relevance 1.08 Pain Relevance 0.49

Despite the ascertainment of the families through at least two melanoma patients, the frequencies of these four variants in unaffected CDKN2A mutation carriers were similar to those reported in control groups from the same populations (12,18).

Neg (unaffected) Regulation (unaffected) of CDKN2A associated with melanoma

12) Confidence 0.44 Published 2010 Journal JNCI Journal of the National Cancer Institute Section Body Doc Link PMC2957428 Disease Relevance 1.04 Pain Relevance 0.44

The median ages at examination among affected and unaffected CDKN2A mutation carriers were 47 and 41 years, respectively, in Europe; 42 and 34 years, respectively, in North America; and 54 and 47 years, respectively, in Australia.

Neg (unaffected) Regulation (affected) of CDKN2A

13) Confidence 0.44 Published 2010 Journal JNCI Journal of the National Cancer Institute Section Body Doc Link PMC2957428 Disease Relevance 0.61 Pain Relevance 0.52

A total of 23 nonsynonymous MC1R variants were detected in affected and unaffected CDKN2A mutation carriers of the 186 melanoma-prone families, and four of these variants (V60L, V92M, R151C, and R160W) showed a frequency more than 5% in these mutation carriers across all continents.

Neg (unaffected) Regulation (affected) of CDKN2A associated with melanocortin 1 receptor and melanoma

14) Confidence 0.44 Published 2010 Journal JNCI Journal of the National Cancer Institute Section Body Doc Link PMC2957428 Disease Relevance 1.09 Pain Relevance 0.49

We also explored whether the association of MC1R variants with melanoma risk differed if the CDKN2A mutations affected p16INK4a alone or both p16INK4 and p14ARF proteins.

Spec (whether) Regulation (affected) of CDKN2A associated with melanocortin 1 receptor and melanoma

15) Confidence 0.44 Published 2010 Journal JNCI Journal of the National Cancer Institute Section Body Doc Link PMC2957428 Disease Relevance 0.74 Pain Relevance 0.39

In our analysis, the associations of MC1R variants with melanoma risk did not differ statistically significantly depending on whether CDKN2A mutations altered only the p16INK4a protein or both p16INK4a and p14ARF proteins.

Spec (whether) Regulation (altered) of p14ARF associated with melanocortin 1 receptor and melanoma

16) Confidence 0.44 Published 2010 Journal JNCI Journal of the National Cancer Institute Section Body Doc Link PMC2957428 Disease Relevance 0.54 Pain Relevance 0.98

Moreover, a number of other genetic alterations for several specific genes including p53, p16INK4a, and Smad4, have been documented [58].

Regulation (alterations) of p16INK4a

17) Confidence 0.44 Published 2011 Journal Journal of Biomedicine and Biotechnology Section Body Doc Link PMC2964042 Disease Relevance 0.80 Pain Relevance 0

We also investigated whether the associations of the frequent MC1R variants and number of MC1R variants with melanoma risk differed according to the type of CDKN2A mutations (mutations affecting p16INK4a protein only vs mutations affecting both p16INK4a and p14ARF proteins).

Regulation (affecting) of p16INK4a associated with melanocortin 1 receptor and melanoma

18) Confidence 0.44 Published 2010 Journal JNCI Journal of the National Cancer Institute Section Body Doc Link PMC2957428 Disease Relevance 0.42 Pain Relevance 1.16

We also investigated whether the associations of the frequent MC1R variants and number of MC1R variants with melanoma risk differed according to the type of CDKN2A mutations (mutations affecting p16INK4a protein only vs mutations affecting both p16INK4a and p14ARF proteins).

Regulation (affecting) of p16INK4a associated with melanocortin 1 receptor and melanoma

19) Confidence 0.44 Published 2010 Journal JNCI Journal of the National Cancer Institute Section Body Doc Link PMC2957428 Disease Relevance 0.41 Pain Relevance 1.21

and 2, thus affecting p16INK4a protein alone or both p16INK4a and p14ARF proteins (7).

Regulation (affecting) of p16INK4a

20) Confidence 0.44 Published 2010 Journal JNCI Journal of the National Cancer Institute Section Body Doc Link PMC2957428 Disease Relevance 1.22 Pain Relevance 0.11

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