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Genetic variation in VEGF family genes and breast cancer risk: a report from the Shanghai Breast Cancer Genetics Study.

ABSTRACT: BACKGROUND:In addition to mediating aspects of physiologic and pathologic angiogenesis, the VEGF family also contributes to carcinogenesis. METHODS:We comprehensively characterized genetic variation across four VEGF family genes and evaluated associations with breast cancer risk with odds ratios (OR) and 95% CIs for participants of the two-stage case-control Shanghai Breast Cancer Genetics Study (SBCGS). Stage 1 evaluated 200 single nucleotide polymorphisms (SNP) across two VEGF ligands (VEGFA and VEGFC) and two VEGF receptors (FLT1/VEGFR1 and KDR/VEGFR2) among 2,079 cases and 2,148 controls. Five SNPs with promising associations were assessed in stage 2 among 4,419 cases and 1,851 controls. RESULTS:Two SNPs were consistently associated with breast cancer risk across our two study stages and were significant in combined analyses. Compared with FLT1 rs9551471 major allele homozygotes (AA), reduced risks were associated with AG (OR = 0.92, 95% CI: 0.84-1.00) and GG (OR = 0.78, 95% CI: 0.64-0.95) genotypes (P(trend) = 0.005). Compared with VEGFA rs833070 major allele carriers (CC or CT), increased risk was associated with TT genotypes (OR = 1.26, 95% CI: 1.05-1.52, P = 0.016). CONCLUSION:Results from our study indicate that common genetic variation in VEGFA and FLT1 (VEGFR1) may contribute to breast cancer susceptibility. IMPACT:Our findings provide clues for future studies on VEGF family genes in relation to cancer susceptibility and survival.

SUBMITTER: Beeghly-Fadiel A

PROVIDER: S-EPMC3336364 | biostudies-literature | 2011 Jan

REPOSITORIES: biostudies-literature

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Genetic variation in VEGF family genes and breast cancer risk: a report from the Shanghai Breast Cancer Genetics Study.

Beeghly-Fadiel Alicia A Shu Xiao-Ou XO Lu Wei W Long Jirong J Cai Qiuyin Q Xiang Yong-Bing YB Zheng Ying Y Zhao Zhongming Z Gu Kai K Gao Yu-Tang YT Zheng Wei W

Cancer epidemiology, biomarkers & prevention : a publication of the American Association for Cancer Research, cosponsored by the American Society of Preventive Oncology 20101130 1

<h4>Background</h4>In addition to mediating aspects of physiologic and pathologic angiogenesis, the VEGF family also contributes to carcinogenesis.<h4>Methods</h4>We comprehensively characterized genetic variation across four VEGF family genes and evaluated associations with breast cancer risk with odds ratios (OR) and 95% CIs for participants of the two-stage case-control Shanghai Breast Cancer Genetics Study (SBCGS). Stage 1 evaluated 200 single nucleotide polymorphisms (SNP) across two VEGF l ...[more]

PMID: 21119072

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Project description:We investigated the association of major comorbidities with breast cancer outcomes using the Shanghai Breast Cancer Survival Study, a population-based, prospective cohort study of Chinese women diagnosed with breast cancer. Analyses included 4,664 women diagnosed with stage I-III incident breast cancer aged 20-75 years (median age = 51) during 2002-2006. Women were interviewed at 3-11 months post-diagnosis (median = 6.4) and followed up by in-person interviews and linkage with the vital statistics registry. Multivariable hazard ratios (HRs) and (95 % confidence intervals (CIs)) for the associations of comorbidities with breast cancer outcomes were estimated using Cox regression models. After a median follow-up of 5.3 years (range: 0.64-8.9), 647 women died (516 from breast cancer) and 632 recurrence/metastases were documented. The main comorbidities reported included: hypertension (22.4 %), chronic gastritis (14.3 %), diabetes mellitus (6.2 %), chronic bronchitis/asthma (5.8 %), coronary heart disease (5.0 %), and stroke (2.2 %). Diabetes was associated with increased risk of total mortality (adjusted HR: 1.40 (1.06-1.85)) and non-breast cancer mortality (adjusted HR: 2.64 (1.63-4.27)), but not breast cancer-specific mortality (adjusted HR: 0.98 (0.68-1.41)), adjusting for socio-demographics, clinical characteristics, selected lifestyle factors, and other comorbidities. Women with a history of stroke had a non-significant increased risk of total mortality (adjusted HR: 1.42 (0.91-2.22)) and a significant increased risk of non-breast cancer mortality (adjusted HR: 2.52 (1.33-4.78)), but not breast cancer-specific mortality (adjusted HR: 0.78 (0.38-1.62)). Overall, none of the comorbidities investigated were significantly associated with recurrence. In this large prospective cohort of breast cancer survivors, diabetes was significantly associated with increased risk of total and non-breast cancer mortality, and history of stroke was associated with increased risk of non-breast cancer mortality.

Dataset Information

Genetic variation in VEGF family genes and breast cancer risk: a report from the Shanghai Breast Cancer Genetics Study.

Publications

Genetic variation in VEGF family genes and breast cancer risk: a report from the Shanghai Breast Cancer Genetics Study.

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