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Thread: Prostate Cancer & Y-DNA Association in Europeans and Ashkenazi Jews

  1. #1
    Unavailable DMXX's Avatar
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    Prostate Cancer & Y-DNA Association in Europeans and Ashkenazi Jews

    Abstract

    Genetic variation on the Y chromosome has not been convincingly implicated in prostate cancer risk. To comprehensively analyze the role of inherited Y chromosome variation in prostate cancer risk in individuals of European ancestry, we genotyped 34 binary Y chromosome markers in 3,995 prostate cancer cases and 3,815 control subjects drawn from four studies. In this set, we identified nominally significant association between a rare haplogroup, E1b1b1c, and prostate cancer in stage I (P = 0.012, OR = 0.51; 95% confidence interval 0.30–0.87). Population substructure of E1b1b1c carriers suggested Ashkenazi Jewish ancestry, prompting a replication phase in individuals of both European and Ashkenazi Jewish ancestry. The association was not significant for prostate cancer overall in studies of either Ashkenazi Jewish (1,686 cases and 1,597 control subjects) or European (686 cases and 734 control subjects) ancestry (P meta = 0.078), but a meta-analysis of stage I and II studies revealed a nominally significant association with prostate cancer risk (P meta = 0.010, OR = 0.77; 95% confidence interval 0.62–0.94). Comparing haplogroup frequencies between studies, we noted strong similarities between those conducted in the US and France, in which the majority of men carried R1 haplogroups, resembling Northwestern European populations. On the other hand, Finns had a remarkably different haplogroup distribution with a preponderance of N1c and I1 haplogroups. In summary, our results suggest that inherited Y chromosome variation plays a limited role in prostate cancer etiology in European populations but warrant follow-up in additional large and well characterized studies of multiple ethnic backgrounds.
    Results (Initial)

    We analyzed 7,810 men from the Cancer Genetic Markers of Susceptibility (CGEMS) scan in stage I of this study. Of the 34 chromosome Y markers genotyped, 26 were observed in our sample (8 markers were monomorphic) ...


    Fig. 1 Chromosome Y haplogroup tree and frequency distribution in control subjects of European ancestry in Stage I. a Chromosome Y tree showing genotyped markers in black and those not genotyped in light grey. Haplogroup names are according to the International Society of Genetic Genealogy (ISOGG) 2011 update. The arrow points to the mutational event which gave rise to the E1b1b1c haplogroup. Stage I studies are the following: CPS-II American Cancer Society Cancer Prevention Study II, ATBC Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study, CeRePP Centre de Recherche pour les Pathologies Prostatiques, and PLCO Prostate, Lung Colorectal and Ovarian Cancer Screening Trial. b The circle plots show frequencies for haplogroups with a derived frequency of 5% or higher in different colors for each Stage I cohort (remaining haplogroups are combined in one group shown in black)
    In conclusion, we found limited evidence for an association between Y chromosome haplogroups and risk of prostate cancer in populations of European and Ashkenazi Jewish ancestry using a large sample set close to 4,000 case–control pairs in Stage I and 2,300 case–control pairs in Stage II. Weak but consistent evidence for a protective effect for haplogroup E1b1b1c was seen in all studies with a nominally significant meta-analysis, thus, calling for additional replication efforts for this haplogroup in populations of Ashkenazi Jewish and European ancestry. The different frequencies seen in subjects from the four stage I studies may limit power to detect true associations for some branches of the Y haplogroup tree. Furthermore, correcting for population substructure based on autosomal SNPs may not be optimal, as Y chromosome inheritance only reflects male lineages that may have somewhat different characteristics throughout human history and population migration as compared to that of females. Although we cannot exclude a role for all chromosome Y haplogroups in prostate cancer etiology, our study has good power to detect common alleles with relatively large effects. Smaller or population specific effects for the haplgroups tested here, or for other haplogroups, could exist and should be studied by testing comprehensive sets of chromosome Y haplogroup markers in additional studies.
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    It seems, therefore, that the Y-Chromosome generally has little to do with prostate cancer risk, implying the genes predisposing to the condition lie elsewhere (auDNA, X-DNA, mtDNA).

    The researchers did note Y-DNA Haplogroup E1b1b1c had a "[weak] protective effect". Although having not read the study in its' entirety, one wonders whether this protection is not in itself a function of autosomal inheritance from E1b1b1c-carrying individuals at various points of European history.

    The findings go against what was a popular tagline in the genetics world several years ago regarding Haplogroup R1a1a and prostate cancer risk. Such a large sample cohort dissuades us from holding that to be the truth, now.

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  3. #2
    Senior Member ilmari's Avatar
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    Out of all of the individuals that I share fully with at 23andMe, I have the highest risk for prostate cancer that I've seen so far.

    Typical results are 17.8 out of 100 for my ethnicity and age.

    My results are 33.3 out of 100.

    I have a 33.3% risk which represents an increased risk of 1.87 times the average mans risk of 17.8%.

    This is not a surprise to me as all of the men in my paternal line have developed prostate cancer and several have developed metastatic prostate cancer that led to a horrible death.

    The group of identified SNPs lie along the q arm of Chromosome 8.
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    In this study run by both the National Cancer Institute (USA) and the National Institute for Health and Welfare (Finland), vitamin E supplementation was found to protect against prostate cancer:

    http://atbcstudy.cancer.gov/pdfs/atbc33010291994.pdf

    Eat your sunflower seeds!

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     Human (09-27-2012), ilmari (08-10-2012)

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    My Dad and all eight of his brothers had prostate cancer, but it was the kind that seldom comes back after removal. 23andMe gives me an elevated chance of getting it too, I monitor my heath closely and take steps to hopefully prevent it.

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    Senior Member ilmari's Avatar
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    Quote Originally Posted by mrjohn12 View Post
    A few days ago My friends father was suffering from a disease and he went to doctor and the diagnosis is saying that he is suffering from Cancer and the type is Prosthetic Cancer . My aunt is also suffering from this disease . I think here I can get an answer of my question . I am watching from some years that the rate of sufferers being increased but why it is being like that . Have there any suggestion by witch we can avoid this ?
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    I assume you meant to say that your aunt is suffering because her husband has prostate cancer, because women have no prostate, or were you talking about some other sort of cancer?
    Genographic Project: N52850
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    Junior Member Human's Avatar
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    Quote Originally Posted by ilmari View Post
    Out of all of the individuals that I share fully with at 23andMe, I have the highest risk for prostate cancer that I've seen so far.

    Typical results are 17.8 out of 100 for my ethnicity and age.

    My results are 33.3 out of 100.

    I have a 33.3% risk which represents an increased risk of 1.87 times the average mans risk of 17.8%.

    This is not a surprise to me as all of the men in my paternal line have developed prostate cancer and several have developed metastatic prostate cancer that led to a horrible death.

    The group of identified SNPs lie along the q arm of Chromosome 8.
    I'm sorry Ilmari. That's terrible.

    At 23andme, I have a 24.4% risk. My father and both grandfathers had prostate cancer.

  9. #7
    Senior Member ilmari's Avatar
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    Well, Human, at least we both can be more vigilant about having things checked out, and following better diets if we aren't already.

    Cheers!
    Genographic Project: N52850
    GenBank: EU784076
    Z62+ Z60+ Z59+ Z58+ P38+ P30+ P19+ M307+ M258+ M253+ M170+ Z73- Z140- P37.2- P259- P109- M72- M26- M227- M223- M21- M161- L803- L573- L338- L22- L211- L1248- L1247-

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