Prodipto Pal

Common variants in 8q24 are associated with risk for prostate cancer and tumor aggressiveness in men of European ancestry

Recent whole genome association studies have independently identified multiple prostate cancer (PC) risk variants on 8q24. We have evaluated association of common variants in this region with PC susceptibility and tumor aggressiveness in a sample of European American men.

Variants in the HEPSIN gene are associated with prostate cancer in men of European origin

There is considerable evidence that genetic factors are involved in prostate cancer susceptibility. We have studied the association of 11 single nucleotide polymorphisms (SNPs) in the HEPSIN gene (HPN) with prostate cancer in men of European ancestry. HPN is a likely candidate in prostate cancer susceptibility, as it encodes a transmembrane cell surface serum protease, which is overexpressed in prostate cancer; HPN is also located on 19q11–q13.2, where linkage is found with prostate cancer susceptibility. In this case-control association study (590 men with histologically verified prostate cancer and 576 unrelated controls, all of European descent), we find significant allele frequency differences between cases and controls at five SNPs that are located contiguously within the gene. A major 11-locus haplotype is significantly associated, which provides further support that HPN is a potentially important candidate gene involved in prostate cancer susceptibility. Association of one of the SNPs with Gleason score is also suggestive of a plausible role of HPN in tumor aggressiveness.

A tagging SNP in INSIG2 is associated with obesity-related phenotypes among Samoans

BackgroundA genome wide association study found significant association of a sequence variant, rs7566605, in the insulin-induced gene 2 (INSIG2) with obesity. However, the association remained inconclusive in follow-up studies. We tested for association of four tagging SNPs (tagSNPs) including this variant with body mass index (BMI) and abdominal circumference (ABDCIR) in the Samoans of the Western Pacific, a population with high levels of obesity.MethodsWe studied 907 adult Samoan participants from a longitudinal study of adiposity and cardiovascular disease risk in two polities, American Samoa and Samoa. Four tagSNPs were identified from the Chinese HapMap database based on pairwise r2of ≥0.8 and minor allele frequency of ≥0.05. Genotyping was performed using the TaqMan assay. Tests of association with BMI and ABDCIR were performed under the additive model.ResultsWe did not find association of rs7566605 with either BMI or ABDCIR in any group of the Samoans. However, the most distally located tagSNPs in Intron 3 of the gene, rs9308762, showed significant association with both BMI (p-value 0.024) and ABDCIR (p-value 0.009) in the combined sample and with BMI (p-value 0.038) in the sample from Samoa.ConclusionAlthough rs7566605 was not significantly associated with obesity in our study population, we can not rule out the involvement of INSIG2 in obesity related traits as we found significant association of another tagSNP in INSIG2 with both BMI and ABDCIR. This study suggests the importance of comprehensive assessment of sequence variants within a gene in association studies.

TGFBR1*6A is not associated with prostate cancer in men of European ancestry.

The TGFBR1*6A (*6A) variant in exon 1 of the TGFBR1 gene has been postulated as a putative tumor susceptibility allele in several studies. We have performed a case–control study in 537 men with histologically verified prostate cancer and in 488 unrelated controls to investigate the association of *6A with prostate cancer. Our results revealed that the frequency of the *6A allele does not differ in men with prostate cancer compared to healthy controls, even in a subset of age-matched cases and controls. There is no compelling evidence for an association of the *6A variant with prostate cancer.