HER2 Codon 655 Polymorphism and Risk of Breast Cancer in African Americans and Whites

Millikan, Robert C.; Eaton, Allison; Worley, Kendra; Biscocho, Lorna; Hodgson, M. Elizabeth; Huang, Wen Yi; Geradts, Joseph; Iacocca, Mary; Cowan, David P.; Conway, Kathleen; Dressler, Lynn G.

doi:10.1023/a:1024068525763

Cited by 69 publications

(80 citation statements)

References 19 publications

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“…Additionally, it also raised a possibility that the risk associated with carrying the HER‐2 valine allele might predominantly affect pre‐ or peri‐menopausal breast cancer 78. Consistent with the above investigations, another study also suggested that that V/V or V/I genotype have a twofold increased risk compared with I/I genotype among women who were both younger than 45 years of age and reported a positive family history of breast cancer (OR = 2.3, 95% CI = 1–5.3) 79. However, some conflicting results emerged, revealing that HER‐2 I655V polymorphism may be a biomarker for breast cancer susceptibility among older women 80.…”

Section: The Her‐2 Mutations Associated With Breast Cancer Risksupporting

confidence: 63%

Analysis of different HER‐2 mutations in breast cancer progression and drug resistance

Sun

Shi

Shen

et al. 2015

J Cellular Molecular Medi

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Studies over the last two decades have identified that amplified human epidermal growth factor receptor (HER‐2; c‐erbB‐2, neu) and its overexpression have been frequently implicated in the carcinogenesis and prognosis in a variety of solid tumours, especially breast cancer. Lots of painstaking efforts were invested on the HER‐2 targeted agents, and significantly improved outcome and prolonged the survival of patients. However, some patients classified as ‘HER‐2‐positive’ would be still resistant to the anti‐HER‐2 therapy. Various mechanisms of drug resistance have been illustrated and the alteration of HER‐2 was considered as a crucial mechanism. However, systematic researches in regard to the HER‐2 mutations and variants are still inadequate. Notably, the alterations of HER‐2 play an important role in drug resistance, but also have a potential association with the cancer risk. In this review, we summarize the possible mutations and focus on HER‐2 variants’ role in breast cancer tumourigenesis. Additionally, the alteration of HER‐2, as a potential mechanism of resistance to trastuzumab, is discussed here. We hope that HER‐2 related activating mutations could potentially offer more therapeutic opportunities to a broader range of patients than previously classified as HER‐2 overexpressed.

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Section: The Her‐2 Mutations Associated With Breast Cancer Risksupporting

confidence: 63%

Analysis of different HER‐2 mutations in breast cancer progression and drug resistance

Sun

Shi

Shen

et al. 2015

J Cellular Molecular Medi

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“…The relationship between the I655V genotype and HER-2 amplification has been suggested in previous studies (29,34), which showed that I655V is associated with HER-2 amplification and/or protein overexpression in breast cancer, although the number of cases was small and the results were not significant. If our result is not an incidental finding, it suggests that polymorphisms other than I655V may be associated with HER-2 protein expression and breast cancer progression.…”

Section: Discussionmentioning

confidence: 75%

“…In addition, no significant associations were found in subgroup analysis [e.g., within younger subjects (<45 years old), those who have a family history, or those with localized or in situ cancer; data not shown]. Previous studies (11,14,15,29) have shown that the association between I655V status and breast cancer risk became more significant in these subgroups.…”

Section: Resultsmentioning

confidence: 80%

A Haplotype Analysis of HER-2 Gene Polymorphisms: Association with Breast Cancer Risk, HER-2 Protein Expression in the Tumor, and Disease Recurrence in Korea

Han¹,

Kang

Lee

et al. 2005

Clinical Cancer Research

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Purpose: A single-nucleotide polymorphism (SNP) in codon 655 of HER-2 has been extensively studied with inconclusive results. The purpose of this study was to investigate the association between common variants of HER-2 and breast cancer risk, HER-2 expression, and survival using a haplotype-based stepwise approach. Experimental Design: Twenty-nine SNPs listed in the National Center for Biotechnology Information database were screened to identify novel polymorphisms of HER-2 gene in 90 healthy Korean women. Six of 29 SNPs were polymorphic and had greater than 10% of minor allele frequencies. Using these six SNPs, linkage disequilibrium and haplotype patterns were characterized. We tested association between the haplotypes and breast cancer in a large case^control study (n = 1,039 cases and 995 controls). Six-hundred two breast cancer patients with follow-up at least 24 months were analyzed for outcome in relation to haplotype. Expression of HER-2 protein was determined by immunohistochemistry in 1,094 cases of invasive breast cancer. Results: All six SNPs showed a strong linkage disequilibrium pattern and were considered to belong to one haplotype block. Two haplotype-tagging SNPs (I655V and P1170A) for three common haplotypes (>5%) were genotyped in cases and controls.The haplotypes and individual SNPs were not associated with breast cancer risk. In patients with at least one copy of haplotype I (the most common haplotype), HER-2 expression was1.5 times higher (P = 0.009) and the prognosis was worse (P = 0.032) compared with patients without having that haplotype. Conclusions: Our results suggest that the currently identified genetic polymorphisms of HER-2 are not associated with an increased risk of breast cancer in Korean women, whereas one haplotype does affect protein expression of the tumor and disease outcome.

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“…Cases of invasive breast cancer were enrolled in two phases (phase 1: 1993-1996, phase 2: 1996-2001) with oversampling of African American and younger women (30). Controls were frequency matched to cases based on age and race (F5 years) using randomized recruitment (31).…”

Section: Methodsmentioning

confidence: 99%

XRCC1 Genotype and Breast Cancer: Functional Studies and Epidemiologic Data Show Interactions between XRCC1 Codon 280 His and Smoking

Pachkowski¹,

Winkel

Kubota

et al. 2006

Cancer Research

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Tobacco smoke produces oxidative and alkylative DNA damage that necessitates repair by base excision repair coordinated by X-ray cross-complementing gene 1 (XRCC1). We investigated whether polymorphisms in XRCC1 alter DNA repair capacity and modify breast cancer risk associated with smoking. To show the functionality of the 280His variant, we evaluated single-strand break (SSB) repair capacity of isogenic Chinese hamster ovary cells expressing human forms of XRCC1 after exposure to hydrogen peroxide (H 2 O 2 ), methyl methanesulfonate (MMS), or camptothecin by monitoring NAD(P)H. We used data from the Carolina Breast Cancer Study (CBCS), a population-based, case-control study that included 2,077 cases (786 African Americans and 1,281 Whites) and 1,818 controls (681 African Americans and 1,137 Whites), to examine associations among XRCC1 codon 194, 280, and 399 genotypes, breast cancer, and smoking. Odds ratios and 95% confidence intervals (95% CI) were calculated by unconditional logistic regression. Only cells expressing the 280His protein accumulated SSB, indicated by NAD(P)H depletion, from both H 2 O 2 and MMS exposures. In the CBCS, positive associations were observed between breast cancer and smoking dose for participants with XRCC1 codon 194 Arg/ Arg (P trend = 0.046), 399 Arg/Arg (P trend = 0.012), and 280 His/His or His/Arg (P trend = 0.047) genotypes. The 280His allele was in strong linkage disequilibrium with 194Arg (Lewontin's D V= 1.0) and 399Arg (D V= 1.0). These data suggest that less common, functional polymorphisms may lie within common haplotypes and drive gene-environment interactions. (Cancer Res 2006; 66(5): 2860-8)

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HER2 Codon 655 Polymorphism and Risk of Breast Cancer in African Americans and Whites

Abstract: The HER2 codon 655 polymorphism may be one of many low-penetrant genes that make a minor contribution to breast cancer, particularly in subgroups of women. Additional large studies, as well as data pooling, will be needed to estimate the contribution of such genes to breast cancer risk.

Cited by 69 publications

References 19 publications

Analysis of different HER‐2 mutations in breast cancer progression and drug resistance

Analysis of different HER‐2 mutations in breast cancer progression and drug resistance

A Haplotype Analysis of HER-2 Gene Polymorphisms: Association with Breast Cancer Risk, HER-2 Protein Expression in the Tumor, and Disease Recurrence in Korea

XRCC1 Genotype and Breast Cancer: Functional Studies and Epidemiologic Data Show Interactions between XRCC1 Codon 280 His and Smoking

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