| 1. |
- Ericson, Ulrika, et al.
(författare)
-
Folate intake, methylenetetrahydrofolate reductase polymorphisms, and breast cancer risk in women from the Malmö Diet and Cancer cohort.
- 2009
-
Ingår i: Cancer Epidemiology Biomarkers & Prevention. - 1538-7755. ; 18:4, s. 1101-1110
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Single nucleotide polymorphisms (SNP) of the folate-metabolizing enzyme methylenetetrahydrofolate reductase (MTHFR) may modify associations between folate intake and breast cancer. We examined if the association between tertiles of dietary folate equivalents (DFE) and breast cancer was different in subgroups according to genotypes of the MTHFR 677 C>T (rs1801133) and 1298A>C (rs1801131) SNPs and if the polymorphisms per se were associated with breast cancer. METHODS: This nested case-control study included 544 incident cases with invasive breast cancer and 1,088 controls matched on age and blood sampling date from the population-based Malmö Diet and Cancer cohort. Genotyping of the MTHFR SNPs was done with PCR-based matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Odds ratios (OR) were obtained by unconditional logistic regression. RESULTS: DFE was positively associated with breast cancer in MTHFR 677CT/TT-1298AA women (P for trend = 0.01) but inversely associated in compound heterozygous women (P for trend = 0.01). Interaction was observed between DFE and the 1298C allele (P = 0.03). The 677T allele was associated with increased breast cancer risk in women above 55 years [multivariate adjusted OR, 1.34; 95% confidence interval (95% CI), 1.01-1.76] and an interaction was observed between the T allele and age (P = 0.03). Homozygosis for the 1298C allele was associated with increased risk in women between 45 and 55 years (multivariate adjusted OR, 1.89; 95% CI, 1.09-3.29). CONCLUSION: In conclusion, a positive association between DFE and breast cancer was observed in MTHFR 677CT/TT-1298AA women but an inverse association was observed in 677CT-1298AC women. The 677T allele was associated with higher breast cancer risk in women above 55 years of age.
|
|
| 2. |
- Ericson, Ulrika, et al.
(författare)
-
Plasma Folate Concentrations Are Positively Associated with Risk of Estrogen Receptor {beta} Negative Breast Cancer in a Swedish Nested Case Control Study.
- 2010
-
Ingår i: Journal of Nutrition. - : Elsevier BV. - 1541-6100 .- 0022-3166. ; 140:9, s. 1661-1668
-
Tidskriftsartikel (refereegranskat)abstract
- Folate's role in breast cancer development is controversial. Not only estrogen receptor (ER) alpha status, but also ERbeta status of tumors may have confounded results from previous epidemiological studies. We aimed to examine associations between plasma folate concentration and postmenopausal breast cancer defined by ER status. This nested case-control study, within the Malmö diet and cancer cohort, included 204 incident breast cancer cases with information on ERalpha and ERbeta status determined by immunochemistry on tissue micro-array sections. Plasma folate concentration was analyzed for the cases and 408 controls (matched on age and blood sample date). Odds ratios (OR) for ER-defined breast cancers in tertiles of plasma folate concentration were calculated with unconditional logistic regression. All tests were 2-sided. Women in the third tertile of plasma folate concentration (>12 nmol/L) had higher incidence of ERbeta- breast cancer than women in the first tertile (OR: 2.67; 95% CI: 1.44-4.92; P-trend = 0.001). We did not observe significant associations between plasma folate concentration and other breast cancer subgroups defined by ER status. We observed a difference between risks for ERbeta+ and ERbeta- cancer (P-heterogeneity = 0.003). Our findings, which indicate a positive association between plasma folate and ERbeta- breast cancer, highlight the importance of taking ERbeta status into consideration in studies of folate and breast cancer. The study contributes knowledge concerning folate's multifaceted role in cancer development. If replicated in other populations, the observations may have implications for public health, particularly regarding folic acid fortification.
|
|
| 3. |
- Harlid, Sophia, 1978-, et al.
(författare)
-
A candidate CpG SNP approach identifies a breast cancer associated ESR1-SNP
- 2011
-
Ingår i: International Journal of Cancer. - : Wiley-Blackwell. - 0020-7136 .- 1097-0215. ; 129:7, s. 1689-1698
-
Tidskriftsartikel (refereegranskat)abstract
- Altered DNA methylation is often seen in malignant cells, potentially contributing to carcinogenesis by suppressing gene expression. We hypothesized that heritable methylation potential might be a risk factor for breast cancer and evaluated possible association with breast cancer for single nucleotide polymorphisms (SNPs) either involving CpG sequences in extended 5'-regulatory regions of candidate genes (ESR1, ESR2, PGR, and SHBG) or CpG and missense coding SNPs in genes involved in methylation (MBD1, MECP2, DNMT1, MGMT, MTHFR, MTR, MTRR, MTHFD1, MTHFD2, BHMT, DCTD, and SLC19A1). Genome-wide searches for genetic risk factors for breast cancers have in general not investigated these SNPs, because of low minor allele frequency or weak haplotype associations. Genotyping was performed using Mass spectrometry-Maldi-Tof in a screening panel of 538 cases and 1,067 controls. Potential association to breast cancer was identified for 15 SNPs and one of these SNPs (rs7766585 in ESR1) was found to associate strongly with breast cancer, OR 1.30 (95% CI 1.17-1.45; p-value 2.1 × 10(-6) ), when tested in a verification panel consisting of 3,211 unique breast cancer cases and 4,223 unique controls from five European biobank cohorts. In conclusion, a candidate gene search strategy focusing on methylation-related SNPs did identify a SNP that associated with breast cancer at high significance.
|
|
| 4. |
- Harlid, Sophia, 1978-, et al.
(författare)
-
Combined effect of low-penetrant SNPs on breast cancer risk
- 2012
-
Ingår i: British Journal of Cancer. - London : Nature Publishing Group. - 0007-0920 .- 1532-1827. ; 106:2, s. 389-396
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Although many low-penetrant genetic risk factors for breast cancer have been discovered, knowledge about the effect of multiple risk alleles is limited, especially in women <50 years. We therefore investigated the association between multiple risk alleles and breast cancer risk as well as individual effects according to age-approximated pre- and post-menopausal status.METHODS: Ten previously described breast cancer-associated single-nucleotide polymorphisms (SNPs) were analysed in a joint European biobank-based study comprising 3584 breast cancer cases and 5063 cancer-free controls. Genotyping was performed using MALDI-TOF mass spectrometry, and odds ratios were estimated using logistic regression.RESULTS: Significant associations with breast cancer were confirmed for 7 of the 10 SNPs. Analysis of the joint effect of the original 10 as well as the statistically significant 7 SNPs (rs2981582, rs3803662, rs889312, rs13387042, rs13281615, rs3817198 and rs981782) found a highly significant trend for increasing breast cancer risk with increasing number of risk alleles (P-trend 5.6 x 10(-20) and 1.5 x 10(-25), respectively). Odds ratio for breast cancer of 1.84 (95% confidence interval (CI): 1.59-2.14; 10 SNPs) and 2.12 (95% CI: 1.80-2.50; 7 SNPs) was seen for the maximum vs the minimum number of risk alleles. Additionally, one of the examined SNPs (rs981782 in HCN1) had a protective effect that was significantly stronger in premenopausal women (P-value: 7.9 x 10(-4)).CONCLUSION: The strongly increasing risk seen when combining many low-penetrant risk alleles supports the polygenic inheritance model of breast cancer. British Journal of Cancer (2012) 106, 389-396. doi:10.1038/bjc.2011.461 www.bjcancer.com Published online 1 November 2011 (C) 2012 Cancer Research UK
|
|
| 5. |
- Harlid, Sophia, 1978-, et al.
(författare)
-
Interactive effect of genetic susceptibility with height, body mass index, and hormone replacement therapy on the risk of breast cancer.
- 2012
-
Ingår i: BMC Women's Health. - : Springer Science and Business Media LLC. - 1472-6874. ; 12
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Breast cancer today has many established risk factors, both genetic and environmental, but these risk factors by themselves explain only part of the total cancer incidence. We have investigated potential interactions between certain known genetic and phenotypic risk factors, specifically nine single nucleotide polymorphisms (SNPs) and height, body mass index (BMI) and hormone replacement therapy (HRT).METHODS: We analyzed samples from three different study populations: two prospectively followed Swedish cohorts and one Icelandic case-control study. Totally 2884 invasive breast cancer cases and 4508 controls were analysed in the study. Genotypes were determined using Mass spectrometry-Maldi-TOF and phenotypic variables were derived from measurements and/or questionnaires. Odds Ratios and 95% confidence intervals were calculated using unconditional logistic regression with the inclusion of an interaction term in the logistic regression model.RESULTS: One SNP (rs851987 in ESR1) tended to interact with height, with an increasingly protective effect of the major allele in taller women (p = 0.007) and rs13281615 (on 8q24) tended to confer risk only in non users of HRT (p-for interaction = 0.03). There were no significant interactions after correction for multiple testing.CONCLUSIONS: We conclude that much larger sample sets would be necessary to demonstrate interactions between low-risk genetic polymorphisms and the phenotypic variables height, BMI and HRT on the risk for breast cancer. However the present hypothesis-generating study has identified tendencies that would be of interest to evaluate for gene-environment interactions in independent materials.
|
|
| 6. |
|
|
| 7. |
- Sonestedt, Emily, et al.
(författare)
-
The protective association of high plasma enterolactone with breast cancer is reasonably robust in women with polymorphisms in the estrogen receptor alpha and beta genes
- 2009
-
Ingår i: Journal of Nutrition. - : Elsevier BV. - 0022-3166 .- 1541-6100. ; 139:5, s. 993-1001
-
Tidskriftsartikel (refereegranskat)abstract
- It is plausible that polymorphisms in the estrogen receptor alpha and beta genes (ESR1 and ESR2) may modulate the association between enterolactone and breast cancer. Seven polymorphisms in ESR1 (rs827422, rs1709184, rs2347867, rs3020328, rs72207, rs2982896, and rs2234693) and 5 polymorphisms in ESR2 (rs915057, rs1269056, rs1256033, rs3020450, and rs3020443) were selected. The risk of breast cancer for these polymorphisms was estimated among 542 cases and 1076 matched controls from the population-based Malmö Diet and Cancer cohort. The joint effect of these polymorphisms and enterolactone was estimated among those individuals about whom we had information on enterolactone blood concentration (365 cases and 728 controls). Breast cancer risk was not significantly associated with any of the selected polymorphisms. We found a tendency for an interaction between a polymorphism in intron 3 of ESR1 (rs2347867) and enterolactone concentration (P = 0.07). Breast cancer and enterolactone concentration were not associated among those homozygous for the major allele (A) (P = 0.93), whereas we found an inverse association among carriers of the minor allele (G) (P = 0.007). None of the other polymorphisms seem to modify the association between enterolactone and breast cancer. This study suggests that the protective association of enterolactone is reasonably robust across the investigated genotypes. The suggested interaction between enterolactone concentration and rs2347867 needs to be confirmed in larger samples.
|
|
