A review of recent articles relating to cancer:

• Breast Cancer and Lewis Blood Group

• Genetic Links to Breast Cancer

• Breast Screening Ineffective?

• Hormone Replacement Therapy is a Carcinogen

• Obesity and Cancer

• Nanotechnology Kills Cancer Cells

• Pineapple and Cancer

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Breast Cancer and Lewis Blood Group

This study in Breast Cancer Research shows a connection between the Lewis blood group and breast cancer.

It is well known that blood group antigens are often altered in the process of cells becoming cancerous. The Lewis blood group antigens (Lewis a and Lewis b) are used to determine secretor status from blood testing, and have isomers (compounds having the same molecular formula but different structures) called Lewis x and Lewis y. The Lewis y antigen is mainly expressed in the growing embryo, in adults it is mainly found in epithelium (tissue composed of a layer of cells, whose functions include secretion, absorption and protection).

Lewis y has been found to be over-expressed in most cancers originating from epithelial tissues, including breast, ovary, pancreas, prostate, colon and some lung cancers.

In the study the patients with invasive breast cancer and higher expression of Lewis y/b antigens tended to have more advanced tumours with a poorer prognosis. Of those patients with higher Lewis y/b expression, those without cancer cells in their lymph nodes were found to have significantly decreased survival.

This is significant for patients being treated for breast cancer who have been found to be lymph node negative, as in addition to their tumour size and grade those with higher Lewis y/b expression may have a poorer prognosis according to the research.

Breast cancer is already known to have a stronger association with ABH secretors (Lewis a-b+) as well as with individuals of blood group A.



Reference:

High expression of Lewisy/b antigens is associated with decreased survival in lymph node negative breast carcinomas

Madjd Z, Parsons T, Watson NFS, Spendlove I, Ellis I, Durrant LG

Breast Cancer Research 2005, 7:R780-R787 (28 July 2005)





Hormone Replacement Therapy is a Carcinogen

The World Health Authority (WHO) has confirmed that Hormone Replacement Therapy (HRT) is cancer-causing. For women taking combined estrogen-progestogen HRT, after five years the risk of breast cancer is increased by four extra cases for every 1000 women.

The WHO also said that the combined estrogen-progestogen contraceptive pill slightly increases the risk of breast, cervix and liver cancer.

The British Medical Journal summarised the risks of using HRT as follows:

• Information about risk of breast cancer with hormone replacement therapy is conflicting

• Data that can be used to derive individual risk are presented to help decision making

• Cumulative absolute risk of breast cancer (to 79 years) falls with increasing age in women who do not take hormone replacement therapy

• Use of hormone replacement therapy increases a woman's cumulative risk only slightly

• The effect on the general incidence of breast cancer incidence would be greater

Incorporating biometric measurements of individuals, such as blood group, secretor status, dermatoglyphics and ear wax type could refine individual risk much further. Patients should not stop taking medication without consulting a licensed healthcare practitioner.

References:

BBC News29th July 2005

Hormone replacement therapy and breast cancer: estimate of riskCoombs NJ, Taylor R, Wilcken N, Boyages J.BMJ 2005;331:347-349





Genetic Link to Breast Cancer

Scientists are finding more genes linked to the development and progression of breast cancer, and also when it is likely to spread to the lungs. Several genes, which are either inherited or altered during a woman's lifetime, have already been identified.

Inherited defective genes such as BRCA1 and BRCA2 account for fewer than 1 in 20 breast cancer cases. In addition a genetic connection links 9q34 (the ABO blood group locus) to breast cancer in individuals of blood group A.

Scientists have now pinpointed another fault which can develop - and have identified four genes which could be the culprit.

The study, in the journal Oncogene, found the fault in a quarter of breast tumours analysed. Researchers at the University of Cambridge examined the tissue of 33 breast tumours and also breast cancer cells grown in the laboratory, focusing on chromosome 8 which had previously been identified as a possible place for cancer-related gene faults. Using microarrays (DNA sequencing), they were able to narrow down which of the hundreds of genes were likely to be actively involved in tumour development.

Four candidate genes were identified on a specific area of chromosome 8. People should have two copies of the whole chromosome, but women with this genetic fault had multiple copies of this particular fragment containing the four potential culprit genes: FLJ14299, C8orf2, BRF2 and RAB11FIP. This pattern was seen in eight out of the 33 tumours studied.

Patients with multiple copies of these chromosome fragments may be at higher risk for having more aggressive tumours, and could be given more intensive treatment.

Another study published in Nature has found a genetic "signature" that could help predict when breast cancer is more likely to spread to the lungs. A "thumbprint" of genetic activity has been identified involving 54 genes that appeared to be particularly associated with lung metastasis.

More than half the patients with this "thumbprint" went on to develop lung metastases, compared with only 10% whose primary tumours did not carry the gene set.



References:

Garcia MJ, Pole JC, Chin SF et. alA 1 Mb minimal amplicon at 8p11-12 in breast cancer identifies new candidate oncogenes.ncogene. 2005 Aug 4;24(33):5235-45.

PMID: 15897872



Genes that mediate breast cancer metastasis to lungMinn AJ, Gupta GP, Siege PM, et. al.Nature 436, 518-524 (28 July 2005)

The Complete Blood Type Encyclopedia





Skin Cancer Court Claims?

Travel companies are in danger of being sued by holidaymakers who develop skin cancer.

People from the cold and cloudy UK who are suffering from skin cancer after holidaying abroad could soon start pushing claims through the courts for a failure of the industry to protect them from the effects of over-exposure to the sun.

A study from Cardiff University has warned that tourism could go the same way as the tobacco industry, who are being sued by smokers with lung cancer.

The sun is not the only influencing factor in skin cancer: research shows individuals of blood group O have a lower survival rate from melanoma than those of other blood groups. If travel companies offer warnings about the risks of the sun, they could also mention that a person's weight, sex and blood group can influence their susceptibility to and survival from melanoma, and recommend drinking green tea (see below, and previous commentary on melanoma). Some think that it is not sun exposure that increases risk of melanoma, but deficiency of antioxidants and other nutrients. Sun exposure is necessary for may people to boost levels of vitamin D.

References:

BBC News



Obesity and Cancer



Women who are obese are up to 36% more likely to develop cancer those of a healthy weight.

Research that looked at nearly 70 000 people in Sweden concludes that almost one in 14 cancers in women are due to overweight and obesity and are therefore avoidable, according to a study in the International Journal of Cancer

"In women, a positive association between BMI [Body Mass Index] and overall cancer risk emerged, mainly driven by the strong effects of elevated BMI on the incidence of endometrial, ovarian and colon cancers as well as melanoma".

This strong adverse effect of BMI on risk of uterine cancer is believed to be due to alterations in the synthesis of hormones caused by increased body fat: both obesity and uterine cancer risk have been associated with decreased synthesis of progesterone in premenopausal women and with increased circulating oestrogens after menopause.

In men no association between BMI and overall cancer risk was shown. This was probably due to the numbers of prostate and respiratory tract cancers, which accounted for more than 40% of all malignancies. Obese men were, however, at a higher risk of developing kidney cancer and colon cancer.

The authors point out that 12% of the men and women in the study were obese, a considerably lower proportion than in the general population in a number of countries, including the United Kingdom and the United States.





Reference:



Body mass index and cancer: Results from the Northern Sweden Health and Disease CohortInternational Journal of Cancer Annekatrin Lukanova 1 2, Ove Björ 3, Rudolf Kaaks et. al.





Breast Screening Ineffective

Breast cancer screening in "real world" situations is not effective in preventing mortality, says a US case control study published in the Journal of the National Cancer Institute:

"Conclusions: In this community-based study, screening history was not associated with breast cancer mortality. However, potential limitations of this study argue for a cautious interpretation of these findings."

Randomised controlled studies have shown that breast cancer screening prevents deaths. Many organisations recommend screening by clinical examination and mammography every year or two for women aged 40 or older.

"We observed no appreciable association between breast cancer mortality and screening history, [regardless of age or risk level]... Our findings may, therefore, reflect a possible reduction in the accuracy of screening as it moves from highly controlled randomised trials to real-life clinical practice."

The study looked at the history of screening in the three years before their diagnosis of cancer in women who died of breast cancer. They compared these screening rates with those in a control group of cancer-free women. Screening rates in the two groups did not differ.

The screening was by clinical examination alone, mammography alone, or clinical examination and mammography. Mortality did not differ according to type of screening.

Despite the findings, the leader of the study Dr Joann Elmore said that she still recommended screening: "Some people say we should pay more attention to women at high risk, but the majority of women who develop breast cancer don't have risk factors."

An accompanying editorial said that breast cancer screening in the community may be less effective than in controlled trial situations because of problems implementing programmes.

Women are now more aware of the importance of checking out small lumps, and better treatment may mean that screening is less necessary than previously, because treatment of later stage cancers may still be effective.

Meanwhile in the New England Journal of Medicine a study showed how certain types of benign breast disease have a higher risk for breast cancer even if there is no family history of breast cancer. Although most non-cancerous breast lumps do not increase future risk of breast cancer, the researchers found faster growing and more abnormal types did.





References:



Efficacy of Breast Cancer Screening in the Community According to Risk LevelJournal of the National Cancer Institute, Vol. 97, No. 14, 1035-1043, July 20, 2005

Benign Breast DisordersSanten RJ, Mansel R.NEJM, Volume 353:275-285





Nanotechnology Kills Cancer Cells



Carbon nanotubules half the width of a DNA molecule are being used to kill cancer cells.

Under normal circumstances near-infra red light passes through the body harmlessly. Researchers found that if they placed a solution of carbon nanotubules under a near-infra red laser beam, the solution heated up to about 70C in two minutes. They then placed the tubules inside cells, and found they were quickly destroyed by the heat generated by the laser beam.

The nanotubules were introduced into cancer cells, but not healthy cells.

The researchers did this by taking advantage of the fact that, unlike normal cells, the surface of cancer cells is covered with receptors for a vitamin known as folate. They coated the nanotubules with folate molecules, making it easy for them to pass into cancer cells, but unable to bind with healthy cells. Exposure to the laser then killed off the diseased cells, but left the healthy ones unharmed.

The researchers said: "Further research will be crucial to see whether these effects can be reproduced in the more complex environment of a tumour and, ultimately, the human body."



Reference:

BBC News





Pineapple and Cancer



Scientists at the Queensland Institute of Medical Research (QIMR) have discovered two molecules from pineapple stems that show anti-tumour activity in laboratory studies.



One molecule called CCS blocks a protein called Ras, which is defective in approximately 30% of all cancers. The other molecule called CCZ, stimulates the body's own immune system to target and kill cancer cells.



The team at QIMR discovered CCS and CCZ while investigating the properties of bromelain, a crushed pineapple stem extract. Bromelain is a rich source of enzymes and is widely used as a meat tenderiser, to clarify beer and tan leather hides. They discovered that bromelain also had some pharmacological properties and could activate specific immune cells while, simultaneously, blocking the immune function of other cells.



"CCS and CCZ are the first examples of proteases that have been shown to modulate cell signal transduction pathways and have specific immunomodulatory activities," said Dr Mynott.

"The way CCS and CCZ work is different to any other drug in clinical use today. Therefore, CCS and CCZ will represent a totally new way of treating disease and potentially a whole new class of anti-cancer agent. In general, products with novel mechanisms of action are more likely to represent real breakthroughs in the treatment or prevention of disease."



Bromelain is also known to have significant antitumour effects when injected directly into mice.



References:



QIMRModulation of murine tumor growth and colonization by bromelaine, an extract of the pineapple plant (Ananas comosum L.).In Vivo. 2005 Mar-Apr;19(2):483-5.Beuth J, Braun JM.

PMID: 15796214