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SMOKING AND RETINOIDS: AN UNEXPECTED SUCCESS STORY?

  1. Top of page
  2. SMOKING AND RETINOIDS: AN UNEXPECTED SUCCESS STORY?
  3. WITH LENTILS AND DHALS AGAINST BREAST CANCER
  4. CANCER RISK: NATURE VS. NURTURE REVISITED

Although vitamin A derivatives are promising agents in cancer prevention and therapy, smokers do not benefit from their clinical application. On pages171–178, Chen and colleagues show how nicotine reverses the anti-proliferative effect of trans retinoic acid (trans-RA) in lung cancer cell lines. Trans-RA is the ligand of the nuclear receptor RAR and leads to the upregulation of the RARβ promoter. For the activation of RARβ transcription, RAR needs to heterodimerize with the orphan receptor COUP-TF. Nicotine, however, prevents RARβ upregulation by inducing TR3, another orphan receptor, that effectively competes with COUP-TF for RAR binding. Indeed, the authors show that antisense-mediated inhibition of TR3 in lung cancer cells prevents the nicotine effect on cell proliferation.

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Figure 1. H460 lung cancer cells stably expressing TR3 anti-sense RNA stay growth inhibited following trans-RA treatment in the presence of nicotine.

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Does this result exclude smokers from retinoid treatment? In an interesting twist, the authors show that, while TR3 cannot partner with RAR, it does effectively partner with the retinoid X receptor (RXR) to potently activate RARβ transcription. In agreement with these observations, they show that the growth-inhibitory effect of SR1237, a synthetic retinoid and selective ligand for RXR, is not reversed by nicotine treatment, but is even slightly enhanced. In the end, in combination with the right retinoid, nicotine might be transformed into a supplement for anticancer therapy.

WITH LENTILS AND DHALS AGAINST BREAST CANCER

  1. Top of page
  2. SMOKING AND RETINOIDS: AN UNEXPECTED SUCCESS STORY?
  3. WITH LENTILS AND DHALS AGAINST BREAST CANCER
  4. CANCER RISK: NATURE VS. NURTURE REVISITED

Vegetarians are protected from breast cancer. Women who had emigrated from India, Pakistan and Bangladesh to England were interviewed in a population-based case-control study (pages238–234. Among them were 240 women with newly diagnosed breast cancer. The detailed analysis showed that women who followed a lifelong diet rich in vegetables, pulses and fiber were less likely to develop breast cancer than meat eaters: the more vegetables consumed daily, the lower the risk. In contrast, increasing meat consumption did not augment the cancer risk. The authors conclude that the protective effect of vegetables, but not the absence of meat, is beneficial for vegetarian women.

It is important to note, however, that in southern Asia diets are determined by religion and maintained lifelong. Most Hindus are vegetarians from early childhood, whereas Muslims do eat meat, except pork. Only a few women in the study stopped eating meat in adulthood, as most Western vegetarians would have. The authors therefore restrict their conclusions to lifelong vegetarians and point out the large amounts of vegetables that need to be consumed. On average, women in the study ate 355 g of vegetables per day, which represents 1.5–5 times the typical daily intake in Western populations.

CANCER RISK: NATURE VS. NURTURE REVISITED

  1. Top of page
  2. SMOKING AND RETINOIDS: AN UNEXPECTED SUCCESS STORY?
  3. WITH LENTILS AND DHALS AGAINST BREAST CANCER
  4. CANCER RISK: NATURE VS. NURTURE REVISITED

Determining the relative role of environmental and genetic factors in the development of cancer remains an important and formidable task. While most cancers arise as the combined products of environmental and genetic factors, increased knowledge of the relative contribution of both genes and the environment will foster the development of more precisely targeted interventional approaches. This issue is likely to receive increased attention in years to come with the mapping of human single nucleotide polymorphisms and increased interest in micronutrients in the development of cancer. Studies of cancer risk in first- and second-generation immigrants, including classic studies on Japanese immigrants to the USA, have determined that environmental factors play a determining etiological role in cancer.

This issue of the International Journal of Cancer features 3 articles by Kari Hemminki and colleagues on this important topic. They have used the Swedish Family Cancer Database to analyze relative cancer risk in more than a million first- and second-generation immigrants to Sweden (pages218–228, 229–237). All cancers were decreased by 5 and 8% for immigrant men and women, respectively, in comparison to the native population (median age at immigration = 23). When the incidence of individual cancers was compared between immigrants and Swedes, many of the cancer rates (stomach, lung and melanoma) appeared to be closer to those of the country of origin than to Sweden.

Interestingly, these differences had disappeared in second-generation immigrants and their rates of cancer were mostly indistinguishable from other Swedes. These observations indicate that the environment during the first 2 decades of life is critical in setting the pattern for cancer development in subsequent life. With rare exceptions, birth in Sweden sets the Swedish pattern for cancer incidence.

In a third study (pages260–266), the same group examined environmental and heritable causes of cancer in 9.6 million individuals using the same database. The importance of genetic effects was estimated by comparing family members that are or are not genetically related. Again, this independent approach indicated that the environment has a principal causative role in all cancers studied, except for thyroid cancer.

These studies clearly point the way to environment factors as major determinants of cancer risk. The next challenge will be to identify the environmental factors playing a critical role in the development of specific cancers.