Λεξικό .. Cancer and Allergy

Cancer and Allergy, 

  There is a long-standing interest in finding whether allergic disorders cause or prevent cancer. There is a possible association between atopy and cancer based on the concept of atopic diseases as a hyper-reactive state of the immune system.

Vojtechova P, Martin RM (2009) meta-analyzed associations of allergies with prostate, breast, and colorectal cancers. They searched MEDLINE, EMBASE, and Web of Science between 1966 and 2008 and eligible reference lists. A total of 16 observational studies were included. Meta-analyses revealed no evidence that asthma, hay fever, or 'any allergy' are associated with cancers of the breast (relative risk, RR = 0.93, 95% CI: 0.73-1.19 for asthma; 1.04, 0.94-1.16 for hay fever; 1.01, 0.94-1.08 for any allergy); prostate (RR = 0.93, 95% CI: 0.76-1.15 for asthma; 0.96, 0.87-1.05 for hay fever; 1.01, 0.87-1.17 for any allergy); or colorectum (RR = 0.95, 95% CI: 0.77-1.16 for asthma; 0.95, 0.86-1.05 for hay fever; 0.94, 0.85-1.04 for any allergy). There was a positive association of atopy (assessed by allergen-specific IgE or skin prick testing) with prostate cancer (RR = 1.43, 95% CI: 1.08-1.91), but not breast (1.18, 0.90-1.55) or colorectal (1.32, 0.69-2.53) cancers. There is little epidemiological support for the immune surveillance theory or antigenic stimulation theory in breast or colorectal carcinogenesis. The findings for prostate cancer warrant further investigation [1].

New blood vessel formation penetrating into solid tumors seems to be required for their growth and metastasis. Several protein growth factors can induce endothelial cell proliferation and angiogenesis, through signal transduction cascades that result in the production of several inflammatory mediators and lipid second messengers such as prostaglandins and Platelet Activating Factor (PAF). PAF is a potent mediator of inflammation that is implicated in several inflammatory pathological conditions such as atherosclerosis, cardiovascular and renal diseases, allergy, AIDS, cancer etc. It exerts its biological activities through G-protein-coupled receptors. The presence of PAF in the microenvironment of tumors may be due to its synthesis from circulating and / or cancer cells. Moreover, cancer cells and activated endothelial cells expose PAF-receptor on their membrane surface. PAF binding on its receptor induces several pathways that result in the onset and development of tumor induced angiogenesis and metastasis. PAF-receptor antagonists have exhibited promising results in vitro and in vivo as anti-angiogenic molecules in several cancer cells and tumors. A dietary profile reach in antioxidants and PAF-inhibitors (such as the Mediterranean Diet) may provide beneficial preventive and protective effects against development, growth and metastatic manifestations of cancer cells, through either their inhibition of PAF activity and / or its biosynthesis. The clarification of factors that may down regulate pathologically increased PAF-levels in a tumor microenvironment may also contribute to the planning of a potent nontoxic preventive and therapeutic approach against cancer [2].

Melanoma is an immunogenic tumour, and since patients with atopic dermatitis (AD) are subjected to local and systemic immunosuppressives, it would be expected to find an influence of AD on the melanoma risk. There is a positive correlation between the number of naevi and melanoma risk, and children and adults with AD have fewer naevi than controls although many patients receive ultraviolet treatment. Synnerstad I, et al, (2008)  investigated the melanoma risk in a retrospective cohort of AD patients compared with the population. A low risk to develop melanoma was found in AD patients. However, the results must be interpreted with caution since the small number of expected cases of melanoma makes the risk estimate sensitive to chance effects. We hypothesize that formation of naevi and progression to melanoma is counteracted by the inflammatory process in the skin of AD patients [3].

Risk factors for central nervous system (CNS) tumours in children remain largely unknown. Evidence of an inverse relationship between atopy and tumour development exists in adults but little is known about childhood tumours. This study aims to examine the risk of childhood CNS tumours given a history of eczema and asthma. Cases of children diagnosed with CNS tumours (n=575) and controls (n=6292) from the UK Childhood Cancer Study (UKCCS) were analysed using conditional logistic regression comparing reported histories of allergic disease. Asthma was statistically significantly and negatively associated with all CNS tumours (odds ratios, OR 0.75, confidence of interval, CI(95%): 0.58-0.97), though this was not observed for eczema (OR 0.94, CI(95%): 0.74-1.18). Individuals who had suffered both asthma and eczema showed the most significant reduction in risk (OR 0.48, CI(95%): 0.28-0.81). Analysis by tumour subtype showed the strongest effect for the medulloblastoma/PNET group. These results may have a biological explanation with raised immunosurveillance in atopic individuals protecting against the development of brain tumours. Alternative explanations might include bias, reverse causality or confounding[4].

Allergy may not be causally associated with the risk of non-Hodgkin lymphoma. The inverse association observed in some case-control studies may arise because non-Hodgkin lymphoma suppresses the immunologic response to allergens [5]. (See Allergy and risk of cancer).

Referenes
1. Vojtechova P, Martin RM. The association of atopic diseases with breast, prostate, and colorectal cancers: a meta-analysis. Cancer Causes Control.2009 Sep;20(7):1091-105. (2009).
2. Tsoupras AB, Iatrou C, Frangia C, Demopoulos CA. The implication of platelet activating factor in cancer growth and metastasis: potent beneficial role of PAF-inhibitors and antioxidants. Infect Disord Drug Targets. 2009 Aug;9(4):390-9.

3. Synnerstad I, Fredrikson M, Ternesten-Bratel A, Rosdahl I. Low risk of melanoma in patients with atopic dermatitis. J Eur Acad Dermatol Venereol.2008 Dec;22(12):1423-8. Epub 2008 Aug 14

4. Harding NJ, Birch JM, Hepworth SJ, McKinney PA. Atopic dysfunction and risk of central nervous system tumours in children. Eur J Cancer. 2008 Jan;44(1):92-9. Epub 2007 Nov 26. 

5. Melbye M, Smedby KE, Lehtinen T, Rostgaard K, Glimelius B, Munksgaard L, Schöllkopf C, Sundström C, Chang ET, Koskela P, Adami HO, Hjalgrim H. Atopy and risk of non-Hodgkin lymphoma. J Natl Cancer Inst.2007 Jan 17;99(2):158-66. Comment in: J Natl Cancer Inst. 2007 Sep 19;99(18):1417.
6.Vajdic CM, Falster MO, de Sanjose S, Martínez-Maza O, Becker N, Bracci PM, Melbye M, Smedby KE, Engels EA, Turner J, Vineis P, Costantini AS, Holly EA, Kane E, Spinelli JJ, La Vecchia C, Zheng T, Chiu BC, Dal Maso L, Cocco P, Maynadié M, Foretova L, Staines A, Brennan P, Davis S, Severson R, Cerhan JR, Breen EC, Birmann B, Cozen W, Grulich AE. Atopic disease and risk of non-Hodgkin lymphoma: an InterLymph pooled analysis. Cancer Res. 2009 Aug 15;69(16):6482-9.