Association between genetic variants in the 8q24 cancer risk regions and circulating levels of androgens and sex hormone-binding globulin.
BACKGROUND
Genome-wide association studies have identified multiple independent regions on chromosome 8q24 that are associated with cancers of the prostate, breast, colon, and bladder.


METHODS
To investigate their biological basis, we examined the possible association between 164 single nucleotide polymorphisms (SNPs) in the 8q24 risk regions spanning 128,101,433-128,828,043 bp, and serum androgen (testosterone, androstenedione, 3alphadiol G, and bioavailable testosterone), and sex hormone-binding globulin levels in 563 healthy, non-Hispanic, Caucasian men (55-74 years old) from a prospective cohort study (the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial). Age-adjusted linear regression models were used to determine the association between the SNPs in an additive genetic model and log-transformed biomarker levels.


RESULTS
Three adjacent SNPs centromeric to prostate cancer risk-region 2 (rs12334903, rs1456310, and rs980171) were associated with testosterone (P < 1.1 x 10(-3)) and bioavailable testosterone (P < 6.3 x 10(-4)). Suggestive associations were seen for a cluster of nine SNPs in prostate cancer risk region 1 and androstenedione (P < 0.05).


CONCLUSIONS
These preliminary findings require confirmation in larger studies but raise the intriguing hypothesis that genetic variations in the 8q24 cancer risk regions might correlate with androgen levels.


CONCLUSIONS
These results might provide some clues for the strong link between 8q24 and prostate cancer risk.
Chu
Lisa W
LW
Division of Cancer Epidemiology and Genetics, National Cancer Institute, NIH, Bethesda, MD, USA.
Meyer
Tamra E
TE
Li
Qizhai
Q
Menashe
Idan
I
Yu
Kai
K
Rosenberg
Philip S
PS
Huang
Wen-Yi
WY
Quraishi
Sabah M
SM
Kaaks
Rudolf
R
Weiss
Jocelyn M
JM
Hayes
Richard B
RB
Chanock
Stephen J
SJ
Hsing
Ann W
AW
D000368:Aged; D000728:Androgens / Q000097:blood*; D002898:Chromosomes, Human, Pair 8; D015179:Colorectal Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000097:blood* / Q000235:genetics* / Q000473:pathology; D010051:Ovarian Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011471:Prostatic Neoplasms / Q000097:blood / Q000235:genetics / Q000473:pathology; D012307:Risk Factors; D012738:Sex Hormone-Binding Globulin / Q000378:metabolism*
D000728:Androgens; D012738:Sex Hormone-Binding Globulin