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Variation in the FGFR2 gene and the effect of a low-fat dietary pattern on invasive breast cancer.

ABSTRACT: BACKGROUND:The Women's Health Initiative dietary modification (DM) trial provided suggestive evidence of a benefit of a low-fat dietary pattern on breast cancer risk, with stronger evidence among women whose baseline diet was high in fat. Single nucleotide polymorphisms (SNP) in the FGFR2 gene relate strongly to breast cancer risk and could influence intervention effects. METHODS:All 48,835 trial participants were postmenopausal and ages 50 to 79 years at enrollment (1993-1998). We interrogated eight SNPs in intron 2 of the FGFR2 gene for 1,676 women who developed breast cancer during trial follow-up (1993-2005). Case-only analyses were used to estimate odds ratios for the DM intervention in relation to SNP genotype. RESULTS:Odds ratios for the DM intervention did not vary significantly with the genotype for any of the eight FGFR2 SNPs (P > or = 0.18). However, odds ratios varied (P < 0.05) with the genotype of six of these SNPs, among women having baseline percent of energy from fat in the upper quartile (> or =36.8%). This variation is most evident for SNP rs3750817, with odds ratios for the DM intervention at 0, 1, and 2 minor SNP alleles of 1.06 [95% confidence intervals (95% CI), 0.80-1.41], 0.53 (95% CI, 0.38-0.74), and 0.62 (95% CI, 0.33-1.15). The nominal significance level for this interaction is P = 0.005, and P = 0.03 following multiple testing adjustment, with most evidence deriving from hormone receptor-positive tumors. CONCLUSION:Invasive breast cancer odds ratios for a low-fat dietary pattern, among women whose usual diets are high in fat, seem to vary with SNP rs3750817 in the FGFR2 gene.

SUBMITTER: Prentice RL

PROVIDER: S-EPMC2806599 | biostudies-literature | 2010 Jan

REPOSITORIES: biostudies-literature

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Variation in the FGFR2 gene and the effect of a low-fat dietary pattern on invasive breast cancer.

Prentice Ross L RL Huang Ying Y Hinds David A DA Peters Ulrike U Cox David R DR Beilharz Erica E Chlebowski Rowan T RT Rossouw Jacques E JE Caan Bette B Ballinger Dennis G DG

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20100101 1

<h4>Background</h4>The Women's Health Initiative dietary modification (DM) trial provided suggestive evidence of a benefit of a low-fat dietary pattern on breast cancer risk, with stronger evidence among women whose baseline diet was high in fat. Single nucleotide polymorphisms (SNP) in the FGFR2 gene relate strongly to breast cancer risk and could influence intervention effects.<h4>Methods</h4>All 48,835 trial participants were postmenopausal and ages 50 to 79 years at enrollment (1993-1998). W ...[more]

PMID: 20056625

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Project description:BackgroundThe Women's Health Initiative Dietary Modification (DM) Randomized Controlled Trial evaluated the effects of a low-fat dietary pattern on chronic disease incidence, with breast cancer and colorectal cancer as primary outcomes. The trial protocol also listed ovarian cancer and endometrial cancer as outcomes that may be favorably affected by the intervention.MethodsA total of 48,835 postmenopausal women were randomly assigned during 1993-1998 to a DM intervention (n = 19,541) or comparison (usual diet; n = 29,294) group and followed up for an average of 8.1 years. The intervention goal was to reduce total fat intake to 20% of energy and to increase consumption of vegetables, fruits, and grains. Cancer outcomes were verified by pathology report review. We used weighted log-rank tests to compare incidence of invasive cancers of the ovary and endometrium, total invasive cancer, and invasive cancers at other sites between the groups. All statistical tests were two-sided.ResultsOvarian cancer risk was lower in the intervention than in the comparison group (P = .03). Although the overall ovarian cancer hazard ratio (HR) was not statistically significantly less than 1.0, the hazard ratio decreased with increasing intervention duration (P(trend) = .01). For the first 4 years, the risk for ovarian cancer was similar in the intervention and control groups (0.52 cases per 1000 person-years in the intervention group versus 0.45 per 1000 person-years in the comparison group; HR = 1.16, 95% confidence interval [CI] = 0.73 to 1.84); over the next 4.1 years, the risk was lower in the intervention group (0.38 cases per 1000 person-years in the intervention group versus 0.64 per 1000 person-years in the comparison group; HR = 0.60, 95% CI = 0.38 to 0.96). Risk of cancer of the endometrium did not differ between the groups (P = .18). The estimated risk of total invasive cancer was slightly lower in the intervention group than in the control group (HR = 0.95, 95% CI = 0.89 to 1.01; P = .10).ConclusionsA low-fat dietary pattern may reduce the incidence of ovarian cancer among postmenopausal women.

Project description:ImportanceIn a randomized clinical trial, a low-fat eating pattern was associated with lower risk of death after breast cancer. However, the extent to which results were driven by dietary influence on survival after breast cancer diagnosis was unknown.ObjectiveTo determine the association of a low-fat dietary pattern with breast cancer overall survival (breast cancer followed by death from any cause measured from cancer diagnosis).Design, setting, and participantsThis is a secondary analysis of the Women's Health Initiative randomized clinical trial that was conducted at 40 US clinical centers enrolling participants from 1993 through 1998. Participants were 48 835 postmenopausal women with no previous breast cancer and dietary fat intake of greater than 32% by food frequency questionnaire.InterventionsParticipants were randomized to a dietary intervention group (40%; n = 19 541) with goals to reduce fat intake to 20% of energy and increase fruit, vegetable, and grain intake or a usual-diet comparison group (60%; n = 29 294). Dietary group participants with incident breast cancers continued to participate in subsequent dietary intervention activities.Main outcomes and measuresBreast cancer overall survival for incident breast cancers diagnosed during the 8.5-year (median) dietary intervention, examined in post hoc analyses after 11.5 years (median) postdiagnosis follow-up.ResultsOf 1764 women diagnosed with breast cancer during the dietary intervention period, mean (SD) age at screening was 62.7 (6.7) years and age at diagnosis was 67.6 (6.9) years. With 516 total deaths, breast cancer overall survival was significantly greater for women in the dietary intervention group than in the usual-diet comparison group (10-year survival of 82% and 78%, respectively; hazard ratio [HR], 0.78; 95% CI, 0.65-0.94; P = .01). In the dietary group there were fewer deaths from breast cancer (68 vs 120; HR, 0.86; 95% CI, 0.64-1.17), other cancers (36 vs 65; HR, 0.76; 95% CI, 0.50-1.17), and cardiovascular disease (27 vs 64; HR, 0.62; 95% CI, 0.39-0.99).Conclusions and relevanceIn women who received a diagnosis of breast cancer during the dietary intervention period, those in the dietary group had increased overall survival. The increase is due, in part, to better survival from several causes of death.Trial registrationClinicalTrials.gov Identifier: NCT00000611.

Project description:BackgroundIntensive dietary intervention programs may lead to benefits in vitality and other components of health quality. The Women's Health Initiative Dietary Modification (DM) intervention includes a large randomized controlled trial of an intensive intervention.ObjectiveTo evaluate whether the intervention is associated with improved health-related quality of life (HRQoL) subscales, overall self-reported health, depression symptoms, cognitive functioning, and sleep quality.DesignThis randomized controlled trial was analyzed as intent to treat.ParticipantsBetween 1993 and 1998, 48,835 women aged 50 to 79 years were recruited by 40 clinical centers across the United States. Eligibility included having fat intake at baseline ≥32% of total calories, and excluded women with any prior colorectal or breast cancer, recent other cancers, type 1 diabetes, or medical conditions with predicted survival <3 years.InterventionGoals were to reduce calories from fat to 20%, increase vegetables and fruit to 5+ servings, and increase grain servings to 6+ servings a day. During the first year, 18 group sessions were held, with quarterly sessions thereafter.Main outcome measuresThe RAND 36-Item Health Survey was used to assess HRQoL at baseline, Year 1, and close-out (about 8 years postrandomization), and estimate differential HRQoL subscale change scores.Statistical analyses performedMean change in HRQoL scores (Year 1 minus baseline) were compared by randomization group using linear models.ResultsAt 1 year, there was a differential change between intervention and comparison group of 1.7 units (95% CI 1.5, 2.0) in general health associated with the intervention. DM intervention improved physical functioning by 2.0 units (95% CI 1.7, 2.3), vitality by 1.9 units (95% CI 1.6, 2.2), and global quality of life by 0.09 units (95% CI 0.07, 0.12). With the exception of global quality of life, these effects were significantly modified by body mass index at baseline.ConclusionsDM intervention was associated with small, but significant improvements in three HRQoL subscales: general health, physical functioning, and vitality at 1 year follow-up, with the largest improvements seen in the women with the greatest baseline body mass index.

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Variation in the FGFR2 gene and the effect of a low-fat dietary pattern on invasive breast cancer.

Publications

Variation in the FGFR2 gene and the effect of a low-fat dietary pattern on invasive breast cancer.

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