The traditional diet of Greece and cancer.

[julierene]

I guess my point was that I watched my mother "juice" herself to her grave - thinking it would extend her life. She got 4 months, and the doctors thought she would have had 6. She was a healthy 33 year old woman with a good BMI and on a healthy food kick like you wouldn't believe... Then her son died at age 12 from Stage 4 Rhabdomyosarcoma, that was originally Stage 2 when he was 5. Then I got cancer at 28, early stage 2a and I was healthy... Then my daughter got cancer at age 5, stage 2 Adrenal Cortical Carcinoma... then she had a local recurrance. She was our healthiest eater, and of course at a normal BMI. Then I had a recurrance, and BOOM stage 4 for me. Then we found out that we had Li-Fraumeni syndrome. Back in 1991, they told us our p53 gene was normal. Now they told us our p53 gene was mutated. The far end of the gene was where the mutation was, which they didn't know about in 1991. So I just hesitate to hear so many hold out hope that diets were the cause of their cancers. For years I tried to "do the right thing" to prevent cancer. I asked the doctor in tears, why I couldn't have prevented it when I was doing so many things to prevent it. He said "Your risk was 80% of developing cancer before the age of 50. In your family, I would guess that it would be more like 80% before the age of 30. With odds like that, diet wouldn't prevent your cancer. I've seen hundreds people try to prevent cancer with diet, knowing they had the 'cancer gene', and failure was almost 100%." His field of study was Brazilian children with adrenal cortical carcinoma with a p53 mutation called Arg337Cys. He also studies genetic retinal cancer that almost 100% get before the age of 5 with the gene. You can probably see now why I am on the other side of the fence. It failed for me, my mother, my brother, my daughter, and probably will fail for my other 2 children, and hundreds of patients of my daughter's doctor. We have all tried to eat the "right diet" and it has failed us all. I think the only case I know of is an author with stage 4 breast cancer, named Jane Plant, who has been cancer free for a while now after practically eliminating cow and dairy products. And then I guess I know about Lance Armstrong, but he ate like 5 apple fritters every day...

[R.B.]

Thank you for your post.

Life has certainly dealt you all a desperately difficult hand, and you appear to be dealing with it very bravely.

I very clearly understand your point and position.

I have never claimed diet will cure cancer. I have just suggested that on a population wide basis it will reduce risks for some, and that specifically that there are a significant number of trials implicating fat intake in cancer risk and inflammatory pathways etc.

I have also always said there that the commonly quoted figure of differential in "western" disease from non "western" populations is about 70%. This leaves a very large 30% for whom it would be reasonable to assume that diet if that is the factor has no effect.

I still hold to a position that there is evidence that balancing the omega threes and sixes will moderate the inflammatory pathways, and assist in maintaining the immune system, general health, and moderate risks based on the trials I have read.

Based on the trials being conducted research organisations are sufficiently interested to explore the impacts of lipids on health, and some products developed in consequence, some products being legislated against in some countries eg trans fats etc.

Again I understand your position, and can only begin to imagine your frustration. Please do not associate me with those that are holding diet as the only way to go, or who does not appreciate the huge advances in medicine.

There is room for both and it is important we do not lose sight that the body is immensely complex and has developed this complexity in relation to its environment and the limiting factors in that environment, and so much is simply not understood.

I wish I had the knowledge and expertise to relate what I have read over the last year to your very specific circumstances but I don't.

I have not begun to walk in your shoes and experience the see-saw of hurt and anguish that you must have been through and continue to face.

Thank you for your post. It is important for all of us to know and try and understand if that is ever possible the impossible difficulties in life that many have to face.

RB


PS please find below the results of a search on the ncbi site for "p53 gene and fats" which might suggest fats have a bearing on P53 activity which may or may not be relevant in your circumstances just in case of any interest to you or your doctor.


http://www.ncbi.nlm.nih.gov/entrez/q...arch&DB=pubmed

1: Wu B, Iwakiri R, Ootani A, Tsunada S, Fujise T, Sakata Y, Sakata H, Toda S, Fujimoto K. Related Articles, Links
Free Full Text Dietary corn oil promotes colon cancer by inhibiting mitochondria-dependent apoptosis in azoxymethane-treated rats.
Exp Biol Med (Maywood). 2004 Nov;229(10):1017-25.
PMID: 15522837 [PubMed - indexed for MEDLINE]

2: Chi TY, Chen GG, Lai PB. Related Articles, Links
Abstract Eicosapentaenoic acid induces Fas-mediated apoptosis through a p53-dependent pathway in hepatoma cells.
Cancer J. 2004 May-Jun;10(3):190-200.
PMID: 15285929 [PubMed - indexed for MEDLINE]

3: Chung FL, Pan J, Choudhury S, Roy R, Hu W, Tang MS. Related Articles, Links
Abstract Formation of trans-4-hydroxy-2-nonenal- and other enal-derived cyclic DNA adducts from omega-3 and omega-6 polyunsaturated fatty acids and their roles in DNA repair and human p53 gene mutation.
Mutat Res. 2003 Oct 29;531(1-2):25-36. Review.
PMID: 14637245 [PubMed - indexed for MEDLINE]

4: Hanibuchi M, Sone S. Related Articles, Links
No abstract [Causative agents for lung carcinogenesis]
Nippon Rinsho. 2002 May;60 Suppl 5:63-6. Review. Japanese. No abstract available.
PMID: 12101751 [PubMed - indexed for MEDLINE]

5: Shabany K, Chiu PC, Raghian A, Chang KW, Solt DB. Related Articles, Links
Abstract Rapid in vivo assay for topical oral cancer chemopreventive agents.
Int J Oncol. 2002 Jul;21(1):159-64.
PMID: 12063563 [PubMed - indexed for MEDLINE]

6: Perjesi P, Pinter Z, Gyongyi Z, Ember I. Related Articles, Links
Abstract Effect of rancid corn oil on some onco/suppressor gene expressions in vivo. A short-term study.
Anticancer Res. 2002 Jan-Feb;22(1A):225-30.
PMID: 12017293 [PubMed - indexed for MEDLINE]

7: Diggle CP, Pitt E, Roberts P, Trejdosiewicz LK, Southgate J. Related Articles, Links
Free Full Text N;-3 and n;-6 polyunsaturated fatty acids induce cytostasis in human urothelial cells independent of p53 gene function.
J Lipid Res. 2000 Sep;41(9):1509-15.
PMID: 10974058 [PubMed - indexed for MEDLINE]

8: Yano S, Sone S. Related Articles, Links
Abstract [Causative agents for lung carcinogenesis]
Nippon Rinsho. 2000 May;58(5):1017-22. Review. Japanese.
PMID: 10824542 [PubMed - indexed for MEDLINE]

9: Taylor DD, Gercel-Taylor C, Weese JL. Related Articles, Links
Abstract Modulation of colon tumor oncogene expression by cancer patient-derived lipids.
J Surg Oncol. 1996 Sep;63(1):46-51.
PMID: 8841466 [PubMed - indexed for MEDLINE]

[mamacze]

A bit late Rhonda, but thank you for your nutritional links...teamed up with RB's data, it was extremely helpful. My sis in law has scleroderma and this information will be helpful to her as well. You and RB are sharing a real wealth of information and "food" for thought!
Love Kim from CT

[R.B.]

Julierene.

Re P53 gene mutation and fats.

The technicalities are beyond me but the generality seems to be that oxidised fats and particularly omega 6 (AA archidonic acid is a product of omega six.) can induce gene mutation, AND it seems to suggest the body may have some ability to repair them...? (thanks I had not seen anything about this subject before)

"HNE-dG adducts were detected exclusively in incubations with AA."

"It has been reported that 4-HNE treatment in human cells induces a high frequency of G.C to T.A mutations at the third base of codon 249 (AGG*) of the p53 gene, a mutational hot spot in human cancers,"

"Formation of trans-4-hydroxy-2-nonenal- and other enal-derived cyclic DNA adducts from omega-3 and omega-6 polyunsaturated fatty acids and their roles in DNA repair and human p53 gene mutation."





One for your doctor if of interest?


RB







http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum

1: Biochemistry. 2003 Jul 1;42(25):7848-54. Related Articles, Links
Click here to read
Mutational spectrum and genotoxicity of the major lipid peroxidation product, trans-4-hydroxy-2-nonenal, induced DNA adducts in nucleotide excision repair-proficient and -deficient human cells.

Feng Z, Hu W, Amin S, Tang MS.

Department of Environmental Medicine, New York University School of Medicine, Tuxedo, New York 10987, USA.

trans-4-Hydroxy-2-nonenal (4-HNE), a major product of lipid peroxidation, is able to interact with DNA to form 6-(1-hydroxyhexanyl)-8-hydroxy-1,N(2)-propano-2'-deoxyguanosine (4-HNE-dG) adducts, but its genotoxicity and mutagenicity remain elusive. It has been reported that 4-HNE treatment in human cells induces a high frequency of G.C to T.A mutations at the third base of codon 249 (AGG*) of the p53 gene, a mutational hot spot in human cancers, particularly in hepatocellular carcinoma. This G.C to T.A transversion at codon 249, however, has been thought to be caused by etheno-DNA adducts induced by the endogenous metabolite of 4-HNE, 2,3-epoxy-4-hydroxynonanal. We have recently found that 4-HNE preferentially forms 4-HNE-dG adducts at the GAGG*C/A sequence in the p53 gene including codon 249 (GAGG*C). Our finding supports the possibility that G.C to T.A mutations at codon 249 may be induced by 4-HNE-dG adducts. To investigate this possibility, we determined the mutational spectrum induced by 4-HNE-dG adducts in the supF gene of shuttle vector pSP189 replicated in human cells. We have found that 4-HNE-dG adducts are mutagenic and genotoxic in human cells, and that G.C to T.A transversions are the most prevalent mutations induced by 4-HNE-dG adducts. Furthermore, 4-HNE-dG adducts induce a significantly higher level of genotoxicity and mutagenicity in nucleotide excision repair (NER)-deficient human and Escherichia coli cells than in NER-proficient cells, indicating that NER is a major pathway for repairing 4-HNE-dG adducts in both human and E. coli cells. Together, these results suggest that 4-HNE-dG adducts may contribute greatly to the G.C to T.A mutation at codon 249 of the p53 gene, and may play an important role in carcinogenesis.

PMID: 12820894 [PubMed - indexed for MEDLINE]


http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum


1: Chem Res Toxicol. 2002 Mar;15(3):367-72. Related Articles, Links
Click here to read
Formation of cyclic deoxyguanosine adducts from omega-3 and omega-6 polyunsaturated fatty acids under oxidative conditions.

Pan J, Chung FL.

Division of Carcinogenesis and Molecular Epidemiology, American Health Foundation, Valhalla, New York 10595, USA.

The discovery of the cyclic 1,N(2)-propanodeoxyguanosine adducts of acrolein (Acr), crotonaldehyde (Cro), and t-4-hydroxy-2-nonenal (HNE) as endogenous DNA lesions from lipid peroxidation has raised questions regarding the role of different types of fatty acids as sources for their formation. In this study, we carried out reactions at pH 7 and 37 degrees C with deoxyguanosine 5'-monophosphate and omega-3 polyunsaturated fatty acids (PUFAs), including docosahexaenoic acid (DHA), linolenic acid (LNA), and eicosapentaenoic acid (EPA); or omega-6 PUFAs, including linoleic acid (LA) and arachidonic acid (AA), each in the presence of ferrous sulfate. The formation of Acr, Cro, and HNE-derived 1,N(2)-propanodeoxyguanosine adducts (Acr-, Cro-, and HNE-dG) in the incubation mixture was determined by reversed-phase HPLC analysis. The results showed that Acr and Cro adducts are primarily derived from omega-3 PUFAs, although Acr adducts are also formed, to a lesser extent, from oxidized AA and LA. HNE-dG adducts were detected exclusively in incubations with AA. The kinetics of the formation of these adducts was determined during incubations for 2 weeks and 5 days. The rate of Acr adduct formation was about 5-10-fold that of Cro adducts, depending on the type of PUFAs, and the rate of formation of HNE adducts from AA was also considerably slower than that of Acr adducts. Unlike other cyclic adducts, the formation of Acr adducts was independent of types of PUFAs, but its yield was proportional to the number of double bonds in the fatty acid. Only one of the isomeric Acr adducts was detected, and its stereoselective formation is consistent with that observed previously in vivo. Two previously unknown cyclic adducts, one derived from pentenal and the other from heptenal, were also detected as products from omega-3 and omega-6 fatty acids, respectively. This study demonstrated the specificity for the formation of the cyclic adducts of Acr, Cro, and HNE and other related enals by oxidation of omega-3 and omega-6 PUFAs. These results may be important for the understanding of the specific roles of different types of fatty acids in tumorigenesis.


http://www.ncbi.nlm.nih.gov/entrez/q...=pubmed_docsum


1: Mutat Res. 2003 Oct 29;531(1-2):25-36. Related Articles, Links
Click here to read
Formation of trans-4-hydroxy-2-nonenal- and other enal-derived cyclic DNA adducts from omega-3 and omega-6 polyunsaturated fatty acids and their roles in DNA repair and human p53 gene mutation.

Chung FL, Pan J, Choudhury S, Roy R, Hu W, Tang MS.

Division of Carcinogenesis and Molecular Epidemiology, Institute for Cancer Prevention, American Health Foundation Cancer Center, Valhalla, NY 10595, USA. fchung@ifcp.us

The cyclic 1,N(2)-propanodeoxyguanosine adducts, derived from alpha,beta-unsaturated aldehydes or enals, including acrolein (Acr), crotonaldehyde (Cro), and trans-4-hydroxy-2-nonenal (HNE), have been detected as endogenous DNA lesions in rodent and human tissues. Collective evidence has indicated that the oxidative metabolism of polyunsaturated fatty acids (PUFAs) is an important pathway for endogenous formation of these adducts. In a recent study, we examined the specific role of different types of fatty acids, omega-3 and omega-6 PUFAs, in the formation of cyclic adducts of Acr, Cro, and HNE. Our studies showed that the incubation of deoxyguanosine 5'-monophosphate with omega-3 or omega-6 fatty acids under oxidative conditions in the presence of ferrous sulfate yielded different amounts of Acr, Cro, and HNE adducts, depending on the types of fatty acids. We observed that Acr- and Cro-dG adducts are primarily formed from omega-3, and the adducts derived from longer chain enals, such as HNE, were detected exclusively from omega-6 fatty acids. Acr adducts are also formed from omega-6 fatty acids, but to a lesser extent; the yields of Acr adducts are proportional to the number of double bonds present in the PUFAs. Two previously unknown cyclic adducts, one from pentenal and the other from heptenal, were detected as products from omega-3 and omega-6 fatty acids, respectively. Because omega-6 PUFAs are known to be involved in the promotion of tumorigenesis, we investigated the role of HNE adducts in p53 gene mutation by mapping the HNE binding to the human p53 gene with UvrABC nuclease and determined the formation of HNE-dG adducts in the gene. The results showed that HNE-dG adducts are preferentially formed in a sequence-specific manner at the third base of codon 249 in the p53 gene, a mutational hotspot in human cancers. The DNA repair study using plasmid DNA containing HNE-dG adducts as a substrate in HeLa cell extracts showed that HNE adducts are readily repaired, and that nucleotide excision repair appears to be a major pathway involved. Together, results of these studies provide a better understanding of the involvement of different PUFAs in DNA damage and their possible roles in tumorigenesis.

Publication Types:

* Review


PMID: 14637245 [PubMed - indexed for MEDLINE]