Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer.
BACKGROUND: Vitamin B(12), holo-haptocorrin, and the folate-pathway single-nucleotide polymorphisms MTR 2756A>G and SHMT1 1420C>T have been associated with an increased risk of prostate cancer. We investigated whether these and other elements of folate metabolism were associated with p...
| Main Authors: | , , , , , , , , , , , , , , |
|---|---|
| Format: | Journal article |
| Language: | English |
| Published: |
2010
|
| _version_ | 1797079538803408896 |
|---|---|
| author | Collin, S Metcalfe, C Refsum, H Lewis, S Smith, G Cox, A Davis, M Marsden, G Johnston, C Lane, J Donovan, J Neal, D Hamdy, F Smith, A Martin, R |
| author_facet | Collin, S Metcalfe, C Refsum, H Lewis, S Smith, G Cox, A Davis, M Marsden, G Johnston, C Lane, J Donovan, J Neal, D Hamdy, F Smith, A Martin, R |
| author_sort | Collin, S |
| collection | OXFORD |
| description | BACKGROUND: Vitamin B(12), holo-haptocorrin, and the folate-pathway single-nucleotide polymorphisms MTR 2756A>G and SHMT1 1420C>T have been associated with an increased risk of prostate cancer. We investigated whether these and other elements of folate metabolism were associated with prostate-specific antigen (PSA) velocity (PSAV) as a proxy measure of prostate cancer progression in men with localized prostate cancer. METHODS: We measured plasma folate, B(12), holo-haptocorrin, holo-transcobalamin, total transcobalamin, and total homocysteine at diagnosis in 424 men (ages 45-70 years) with localized prostate cancer in a U.K.-wide population-based cohort. Thirteen folate-pathway single-nucleotide polymorphisms were genotyped for 311 of these men. Postdiagnosis PSAV (continuous measure and with a threshold set a priori at 2 ng/mL/y) was estimated from repeat PSA measurements. RESULTS: Median follow-up time was 2.5 (range, 0.8-5.6) years. Vitamin B(12), holo-haptocorrin, holo-transcobalamin, total transcobalamin, and total homocysteine were not associated with postdiagnosis PSAV. Folate was associated with an increased risk of PSAV >2 ng/mL/y [odds ratio (OR) per unit increase in log(e) concentration, 1.57; 95% confidence interval (95% CI), 0.98-2.51; P = 0.06]. MTRR 66A>G (rs1801394) was associated with a reduced risk (recessive model OR, 0.33; 95% CI, 0.11-0.97; P = 0.04), and SHMT1 1420C>T (rs1979277) with an increased risk (per-allele OR, 1.49; 95% CI, 0.93-2.37; P = 0.09) of PSAV >2 ng/mL/y. CONCLUSIONS: We found weak evidence that higher folate levels may be associated with faster progression of localized prostate cancer. IMPACT: Long-term follow-up is needed to test associations with metastases and mortality, and the observed genetic effects require replication. |
| first_indexed | 2024-03-07T00:47:22Z |
| format | Journal article |
| id | oxford-uuid:85273a2e-d204-42ce-8e47-cafd42d1dc26 |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T00:47:22Z |
| publishDate | 2010 |
| record_format | dspace |
| spelling | oxford-uuid:85273a2e-d204-42ce-8e47-cafd42d1dc262022-03-26T21:55:30ZAssociations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer.Journal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:85273a2e-d204-42ce-8e47-cafd42d1dc26EnglishSymplectic Elements at Oxford2010Collin, SMetcalfe, CRefsum, HLewis, SSmith, GCox, ADavis, MMarsden, GJohnston, CLane, JDonovan, JNeal, DHamdy, FSmith, AMartin, RBACKGROUND: Vitamin B(12), holo-haptocorrin, and the folate-pathway single-nucleotide polymorphisms MTR 2756A>G and SHMT1 1420C>T have been associated with an increased risk of prostate cancer. We investigated whether these and other elements of folate metabolism were associated with prostate-specific antigen (PSA) velocity (PSAV) as a proxy measure of prostate cancer progression in men with localized prostate cancer. METHODS: We measured plasma folate, B(12), holo-haptocorrin, holo-transcobalamin, total transcobalamin, and total homocysteine at diagnosis in 424 men (ages 45-70 years) with localized prostate cancer in a U.K.-wide population-based cohort. Thirteen folate-pathway single-nucleotide polymorphisms were genotyped for 311 of these men. Postdiagnosis PSAV (continuous measure and with a threshold set a priori at 2 ng/mL/y) was estimated from repeat PSA measurements. RESULTS: Median follow-up time was 2.5 (range, 0.8-5.6) years. Vitamin B(12), holo-haptocorrin, holo-transcobalamin, total transcobalamin, and total homocysteine were not associated with postdiagnosis PSAV. Folate was associated with an increased risk of PSAV >2 ng/mL/y [odds ratio (OR) per unit increase in log(e) concentration, 1.57; 95% confidence interval (95% CI), 0.98-2.51; P = 0.06]. MTRR 66A>G (rs1801394) was associated with a reduced risk (recessive model OR, 0.33; 95% CI, 0.11-0.97; P = 0.04), and SHMT1 1420C>T (rs1979277) with an increased risk (per-allele OR, 1.49; 95% CI, 0.93-2.37; P = 0.09) of PSAV >2 ng/mL/y. CONCLUSIONS: We found weak evidence that higher folate levels may be associated with faster progression of localized prostate cancer. IMPACT: Long-term follow-up is needed to test associations with metastases and mortality, and the observed genetic effects require replication. |
| spellingShingle | Collin, S Metcalfe, C Refsum, H Lewis, S Smith, G Cox, A Davis, M Marsden, G Johnston, C Lane, J Donovan, J Neal, D Hamdy, F Smith, A Martin, R Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer. |
| title | Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer. |
| title_full | Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer. |
| title_fullStr | Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer. |
| title_full_unstemmed | Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer. |
| title_short | Associations of folate, vitamin B12, homocysteine, and folate-pathway polymorphisms with prostate-specific antigen velocity in men with localized prostate cancer. |
| title_sort | associations of folate vitamin b12 homocysteine and folate pathway polymorphisms with prostate specific antigen velocity in men with localized prostate cancer |
| work_keys_str_mv | AT collins associationsoffolatevitaminb12homocysteineandfolatepathwaypolymorphismswithprostatespecificantigenvelocityinmenwithlocalizedprostatecancer AT metcalfec associationsoffolatevitaminb12homocysteineandfolatepathwaypolymorphismswithprostatespecificantigenvelocityinmenwithlocalizedprostatecancer AT refsumh associationsoffolatevitaminb12homocysteineandfolatepathwaypolymorphismswithprostatespecificantigenvelocityinmenwithlocalizedprostatecancer AT lewiss associationsoffolatevitaminb12homocysteineandfolatepathwaypolymorphismswithprostatespecificantigenvelocityinmenwithlocalizedprostatecancer AT smithg associationsoffolatevitaminb12homocysteineandfolatepathwaypolymorphismswithprostatespecificantigenvelocityinmenwithlocalizedprostatecancer AT coxa associationsoffolatevitaminb12homocysteineandfolatepathwaypolymorphismswithprostatespecificantigenvelocityinmenwithlocalizedprostatecancer AT davism associationsoffolatevitaminb12homocysteineandfolatepathwaypolymorphismswithprostatespecificantigenvelocityinmenwithlocalizedprostatecancer AT marsdeng associationsoffolatevitaminb12homocysteineandfolatepathwaypolymorphismswithprostatespecificantigenvelocityinmenwithlocalizedprostatecancer AT johnstonc associationsoffolatevitaminb12homocysteineandfolatepathwaypolymorphismswithprostatespecificantigenvelocityinmenwithlocalizedprostatecancer AT lanej associationsoffolatevitaminb12homocysteineandfolatepathwaypolymorphismswithprostatespecificantigenvelocityinmenwithlocalizedprostatecancer AT donovanj associationsoffolatevitaminb12homocysteineandfolatepathwaypolymorphismswithprostatespecificantigenvelocityinmenwithlocalizedprostatecancer AT neald associationsoffolatevitaminb12homocysteineandfolatepathwaypolymorphismswithprostatespecificantigenvelocityinmenwithlocalizedprostatecancer AT hamdyf associationsoffolatevitaminb12homocysteineandfolatepathwaypolymorphismswithprostatespecificantigenvelocityinmenwithlocalizedprostatecancer AT smitha associationsoffolatevitaminb12homocysteineandfolatepathwaypolymorphismswithprostatespecificantigenvelocityinmenwithlocalizedprostatecancer AT martinr associationsoffolatevitaminb12homocysteineandfolatepathwaypolymorphismswithprostatespecificantigenvelocityinmenwithlocalizedprostatecancer |