Vitamin D receptor gene polymorphisms and cancer risk
Maturitas 2015; 81: 256-65
Over the past few years, vitamin D receptors have been found in every cell of the body. I think the story of what vitamin D really does is only just beginning to be unravelled.
This meta-analysis shows that one of the five vitamin D receptor variants (FokI polymorphism) was significantly associated with an increased risk for ovarian and breast cancers. The BsmI polymorphism was associated with a decreased risk for developing these cancers. Specific vitamin D receptor polymorphisms may be potential ovarian and breast cancer risk factors.
BRCA1 and BRCA2 genes are now screened for in women at a young age with a particularly strong family history of breast cancer. However, these genes only account for a tiny percentage of all breast cancers.
Other significant factors, such as estrogen exposure (early menarche, late menopause or combined HRT), age when pregnant, breastfeeding, smoking, alcohol intake and obesity, are more significant in most women in the developed world. I suspect looking at vitamin D receptors will be incorporated into genetic screening over the next decade.
Genomic analysis of diffuse lower-grade gliomas
N Engl J Med 2015; 372: 2481-98
Patients diagnosed with glioma may receive confusing or conflicting information about what this means in terms of prognosis.
This is understandable, because diffuse low- and intermediate-grade gliomas (which together make
up the lower-grade gliomas, WHO grades II and III) have highly variable clinical behaviour that is not adequately predicted on the basis of histology alone. Some are indolent, slow-growing tumours; others quickly progress into glioblastomas, with a very poor outcome.
This study performed a genome-wide analysis of 293 lower-grade gliomas from adults, incorporating exome sequence, DNA copy number, DNA methylation, messenger RNA expression, microRNA expression and targeted protein expression.
Patients who had lower-grade gliomas with an IDH mutation and 1p/19q co-deletion had the most
favourable clinical outcomes. Most patients with lower-grade gliomas without an IDH mutation had a
clinical path similar to those found with a primary glioblastoma.
The important result from this research is a much tighter correlation between genetic mutations and clinical outcome than the reported cell histology might indicate.
Phosphodiesterase-5 inhibitors and risk of malignant melanoma
JAMA 2015; 313(24): 2449-55
Part of the pathway implicated in the development of malignant melanoma is also the target for phosphodiesterase type 5 (PDE5) inhibitors, used as oral erectile dysfunction medications.
In this nationwide population-nested, case-controlled study in Sweden, involving more than
4,000 men with melanoma, the most interesting result was the increased risk of melanoma in men taking PDE5 inhibitors (OR 1.21).
The most pronounced increase in risk was observed in men who had filled only a single prescription
(OR 1.32), but was not significant among men with multiple filled prescriptions (for two to five prescriptions, OR 1.14), nor for men who had taken more than six prescriptions (OR 1.17).
This raises more questions than it answers. There is a modest rise in melanoma with PDE5 inhibitors,
but the greatest effect with the least use must mean this is a marker for behaviour, for example, sun exposure, rather than a biochemical effect of the drug. I think long-term users of erectile dysfunction drugs can be reassured, along with a discussion about sensible sun exposure.
Do women seeking termination need pre-abortion counselling?
J Fam Plann Reprod Health Care 2015; 41: 181-5
This study asks if it would be useful for all women to have obligatory pre-abortion counselling. At present this is voluntary.
In the study, anonymous feedback was provided by 201 women attending a clinic in Edinburgh.
Only 9% of the women had availed themselves of counselling services and only one woman used a pro-life charity, the rest using NHS services. A total of 22% claimed not to know counselling was available. The vast majority (69%) did not want counselling as they were certain about their decision.
This small sample indicated that most women do not wish to have counselling pre-abortion. Some respondents said they would prefer face-to-face counselling, rather than telephone or internet services.
It seems wise to focus resources on high quality face-to-face counselling for the <10% of women who want counselling, rather than dilute the service to give it to everyone, whether they would like it or not.
- Dr Hope is a GP in Woodstock, Oxfordshire, and a member of our team who regularly review the journals
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