Table 3.
Multivariable adjusted* haplotype analysis of genes in the one-carbon metabolism pathway and ovarian cancer risk among 1,770 Caucasian subjects, Mayo Clinic, MN and Duke University, NC, 1999–2006
Haplotype | Global P† | Estimated haplotype frequency | Score test ‡ | Haplotype P§ | |
---|---|---|---|---|---|
No. | Allele combinations | ||||
MTR|| | 0.04 | ||||
1 | AGCTAATT | 0.12 | −2.29 | 0.02 | |
2 | AACCGCCG | 0.14 | −1.45 | 0.14 | |
3 | AGTCACCG | 0.002 | −0.69 | 0.49 | |
4 | AGCTACCG | 0.004 | −0.07 | 0.94 | |
5 | GGCTAATT | 0.26 | 0.26 | 0.79 | |
6 | AGCCGCCG | 0.04 | 0.40 | 0.69 | |
7 | AGTTACCG | 0.38 | 0.79 | 0.43 | |
8 | AGTTAATT | 0.01 | 1.03 | 0.30 | |
9 | AGTTACCT | 0.002 | 1.07 | 0.28 | |
10 | GGCTACCG | 0.01 | 1.17 | 0.24 | |
11 | AGCTACCT | 0.02 | 2.47 | 0.01 | |
SHMT1** | 0.05 | ||||
1 | GTCAG | 0.33 | −2.56 | 0.01 | |
2 | ATCGG | 0.01 | −0.44 | 0.66 | |
3 | ACTAG | 0.31 | −0.01 | 0.99 | |
4 | GTCAA | 0.10 | 1.21 | 0.23 | |
5 | GTCGG | 0.25 | 2.14 | 0.03 |
Adjusted for age (<40, 40–49, 50–59, 60–69, 70+), state (MN, IA, WI, IL, ND/SD, NC), BMI in kg/m2 (<23, 23–25.9, 26–28.9, 29+), postmenopausal hormone use (never, 1–60 months, 60+ months), oral contraceptive use (never, 1–48 months, 48+ months) and parity/age at first birth (nulliparous, 1–2/≤20 yrs, 1–2/>20 yrs, 3+/≤20 yrs, 3+/>20 yrs)
P value from the global score test of Schaid et al (36) across haplotypes.
Score statistics comparing haplotype of interest with all other haplotypes combined. Negative values imply decreased risk of ovarian cancer, whereas positive values imply increased risk.
P value comparing haplotype of interest with all other haplotypes combined.
Haplotype-forming SNPs in MTR are rs12759827 (A>G), rs4659723 (G>A), rs4659724 (C>T), rs10925250 (T>C), rs1805087 (A>G), rs2853523 (C>A), rs1050993 (C>T), rs6676866 (G>T). Different alleles between significant haplotypes are underlined.
Haplotype-forming SNPs in SHMT1 are rs921986 (G>A), rs12952556 (T>C), rs1979277 (C>T), rs9909104 (A>G), rs2273026 (G>A). Different alleles between significant haplotypes are underlined.