METHODS: In total, DNA samples were obtained from 14,525 case subjects with invasive EOC and from 23,447 controls from 43 sites in the Ovarian Cancer Association Consortium (OCAC). Two hundred seventy nine SNPs, representing 131 genes, were genotyped using an Illumina Infinium iSelect BeadChip as part of the Collaborative Oncological Gene-environment Study (COGS). SNP analyses were conducted using unconditional logistic regression under a log-additive model, and the FDR q<0.2 was applied to adjust for multiple comparisons.
RESULTS: The most significant evidence of an association for all invasive cancers combined and for the serous subtype was observed for SNP rs17216603 in the iron transporter gene HEPH (invasive: OR = 0.85, P = 0.00026; serous: OR = 0.81, P = 0.00020); this SNP was also associated with the borderline/low malignant potential (LMP) tumors (P = 0.021). Other genes significantly associated with EOC histological subtypes (p<0.05) included the UGT1A (endometrioid), SLC25A45 (mucinous), SLC39A11 (low malignant potential), and SERPINA7 (clear cell carcinoma). In addition, 1785 SNPs in six genes (HEPH, MGST1, SERPINA, SLC25A45, SLC39A11 and UGT1A) were imputed from the 1000 Genomes Project and examined for association with INV EOC in white-European subjects. The most significant imputed SNP was rs117729793 in SLC39A11 (per allele, OR = 2.55, 95% CI = 1.5-4.35, p = 5.66x10-4).
CONCLUSION: These results, generated on a large cohort of women, revealed associations between inherited cellular transport gene variants and risk of EOC histologic subtypes.
METHODS: Cross-sectional study of Malaysian ambulant CWE on antiseizure medication for >1 year. Sixteen SNPs in 8 genes (GC, VDR, CYP2R1, CYP24A1, CYP27B1, CYP27A1, CYP3A4, NADSYN1/DHCR7) were genotyped. Linear and logistic regression models and co-variates adjusted analyses were used. SNPs with significant associations were further analysed in a group of ethnically-matched healthy Malaysian children.
RESULTS: 239 CWE were recruited (52.7% Malay, 24.3% Chinese and 23.0% Indian) with mean serum 25(OH)D of 58.8 nmol/L (SD 25.7). Prevalence of vitamin D deficiency (≤37.5 nmol/L) was 23.0%. Minor allele of GC-rs4588-A was associated with lower serum 25(OH)D in the meta-analysis of both CWE (β -8.11, P = 0.002) and Malaysian healthy children (β -5.08, P < 0.001), while VDR-rs7975232-A was significantly associated with reduced odds of vitamin D deficiency in Malay subgroup of CWE (OR: 0.16; 95% CI: 0.06-0.49; P = 0.001) and this association was not found in the healthy children group.
CONCLUSIONS: Our results suggest that GC-rs4588 is associated with lower serum 25(OH)D concentration in both Malaysian CWE and healthy children, while VDR-rs7975232A is associated with lower risk of vitamin D deficiency in Malaysian CWE of Malay ethnicity. Our findings may assist in the genetic risk stratification of low vitamin D status among CWE.