Genomic risk, prostate cancer, endometrial cancer, linkage?

Under the “And this helps me how?” column we can now add the topic of a possible genetic link between endometrial cancer and prostate cancer (maybe).

According to a new paper from Spurdle et al., just published in Nature Genetics, a specific “protective” polynucleotide sequence  at a locus (rs4430796) close to the HNF1B region of the genome of women with cancer of the endometrium (now also being called “womb cancer”) is associated with a 15 to 18 percent reduction in the likelihood that women who carry this polynucleotide sequence will contract endometrial cancer compared to women who carry the “normal” or “wild type” polynucleotiode sequence.

In an earlier study, it has already been shown that a “protective” polynucleotide sequence at the same locus in the genome of men with prostate cancer was associated with a 21 percent reduction in risk for prostate cancer compared to men who carried the “normal” or “wild type” sequence.

Now what the researchers are carefully not saying is that the genetic alterations associated with a reduced risk for endometrial cancer are exactly the same as the genetic alterations that lead to reduced risk for prostate cancer. All that they are saying is that three of 47 single polynucleotide polymorphisms (SNPs) in the women at reduced risk for endometrial  cancer occur in the same genetic region (rs4430796, close to region HNF1B in 17q12) as genetic polymorphisms that lead to reduced risk for prostate cancer.

Now it is certainly of intellectual interest that a small number of SNPs in a reasonably well-defined region of the DNA on a specific chromosome (chromosome 17 to be precise) can be associated with reduction in risk for uterine cancer (found only in women) and prostate cancer (found only in men), but we should be very cautious about over-interpretation of such a finding.

Professor Easton, who is the Director of Cancer Research at the Genetic Epidemiology Unit at the University of Cambridge, an the senior author of this multi-author, is quoted on (a University of Cambridge web site) as stating that: “This study is the first to highlight a potential link between womb cancer in women and prostate cancer in men, providing new insight into the underlying genes and mechanisms that lead to the development of both diseases.”

While that statement is arguably true, it is also arguably pushing the envelope of truth too. It might have been a more accurate statement if he had said, “This study is the first to demonstrate the possibility that similar genetic alterations can be associated with a reduction in risk for two very different types of sex-specific genitourinaryc cancers — one in men and the other in women.” This statement is certainly true, but there is no suggestion that the association is actually biologically or clinically significant — which we don’t know as yet.

And this helps you how? As yet, we haven’t a clue. We do know, however, that just as prostate cancer is the most common malignancy of the male urogenital tract in men in the developed world, endometrial cancer is the most common malignancy of the female genital tract in developed countries.

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