TY - JOUR
T1 - Y chromosome haplogroups and prostate cancer in populations of European and Ashkenazi Jewish ancestry
AU - Wang, Zhaoming
AU - Parikh, Hemang
AU - Jia, Jinping
AU - Myers, Timothy
AU - Yeager, Meredith
AU - Jacobs, Kevin B.
AU - Hutchinson, Amy
AU - Burdett, Laurie
AU - Ghosh, Arpita
AU - Thun, Michael J.
AU - Gapstur, Susan M.
AU - Ryan Diver, W.
AU - Virtamo, Jarmo
AU - Albanes, Demetrius
AU - Cancel-Tassin, Geraldine
AU - Valeri, Antoine
AU - Cussenot, Olivier
AU - Offit, Kenneth
AU - Giovannucci, Ed
AU - Ma, Jing
AU - Stampfer, Meir J.
AU - Michael Gaziano, J.
AU - Hunter, David J.
AU - Dutra-Clarke, Ana
AU - Kirchhoff, Tomas
AU - Alavanja, Michael
AU - Freeman, Laura B.
AU - Koutros, Stella
AU - Hoover, Robert
AU - Berndt, Sonja I.
AU - Hayes, Richard B.
AU - Agalliu, Ilir
AU - Burk, Robert D.
AU - Wacholder, Sholom
AU - Thomas, Gilles
AU - Amundadottir, Laufey
N1 - Funding Information:
Acknowledgments This study was supported by the Intramural Research Program of the Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health (NIH). The authors acknowledge and thank both staV and participants in all studies for donating their time and making this study possible. The authors acknowledge support and constructive comments from Dr. Stephen J.
PY - 2012/7
Y1 - 2012/7
N2 - 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.
AB - 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.
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U2 - 10.1007/s00439-012-1139-5
DO - 10.1007/s00439-012-1139-5
M3 - Article
C2 - 22271044
AN - SCOPUS:84862728637
SN - 0340-6717
VL - 131
SP - 1173
EP - 1185
JO - Human Genetics
JF - Human Genetics
IS - 7
ER -
