The clinicopathological significance and drug target potential of FHIT in breast cancer, a meta-analysis and literature review

Figures & data

Table 1 Basic characteristics of the included studies

Study	Country	Patients (n)	Methods	Primary aim	Methylation site	FHIT expression
Zaki et al^Citation32	Egypt	30	MSP	Determine the association between FHIT methylation and clinicopathological features	Promoter, CpG islands	−
Syeed et al^Citation4	India	130	PCR-SSCP	Study mutational and promoter hypermethylation status of FHIT in BC	Promoter	−
Raish et al^Citation33	India	379	MSP/immunochemistry, Western blot	Investigate the relationship of p16 and FHIT methylation with PR and ER in patients with BC	Promoter, CpG islands	+
Naqvi et al^Citation34	India	232	MSP/RT-PCR, Northern blot	Identify specific 5′CpG island methylation signatures of FHIT and p16 genes and their potential diagnostic relevance in BC	Promoter, CpG islands	+
Zhao et al^Citation35	People’s Republic of China	50	MSP/RT-PCR, immunochemistry	Investigate whether abnormal FHIT methylation downregulates the expression of its mRNA and protein		+
Iliopoulos et al^Citation36	USA	28	MSP	Study fragile genes as biomarkers: epigenetic control of WWOX and FHIT in lung, breast, and bladder cancer	Intron	−
Yang et al^Citation37	Japan	46	MSP/immunochemistry	Study two-hit inactivation of FHIT by loss of heterozygosity and hypermethylation in BC		+

Abbreviations: BC, breast cancer; mRNA, messenger RNA; MSP, methylation-specific polymerase chain reaction; PCR-SSCP, polymerase chain reaction single-strand conformation polymorphism; RT-PCR, reverse transcription polymerase chain reaction; ER, estrogen receptor; PR, progesterone receptor.

Figure 1 Schematic flow diagram for selection of included studies.

Figure 2 Forest plot for FHIT hypermethylation in IDC and benign breast disease.

Abbreviations: IDC, invasive ductal carcinoma; df, degrees of freedom; CI, confidence interval; M–H, Mantel–Haenszel.

Figure 3 Forest plot for FHIT hypermethylation in different stages of BC.

Abbreviations: BC, breast cancer; CI, confidence interval; df, degrees of freedom; M–H, Mantel–Haenszel.

Figure 4 Forest plot for FHIT hypermethylation in ER-positive and -negative BC.

Abbreviations: BC, breast cancer; CI, confidence interval; df, degrees of freedom; M–H, Mantel–Haenszel; ER, estrogen receptor.

Figure 5 Forest plot for FHIT hypermethylation in PR-positive and -negative BC.

Abbreviations: BC, breast cancer; CI, confidence interval; df, degrees of freedom; M–H, Mantel–Haenszel; PR, progesterone receptor.

Figure 6 Forest plot for FHIT hypermethylation in postmenopausal and premenopausal BC.

Abbreviations: BC, breast cancer; CI, confidence interval; df, degrees of freedom; M–H, Mantel–Haenszel.

Figure 7 Funnel plot for publication bias.

Notes: (A) FHIT hypermethylation in IDC and benign breast disease; (B) FHIT methylation in different stages of BC; (C) FHIT hypermethylation in ER-positive and -negative BC; (D) FHIT hypermethylation in PR-positive and -negative BC; (E) FHIT hypermethylation in postmenopausal and premenopausal BC.
Abbreviations: BC, breast cancer; IDC, invasive ductal carcinoma; SE, standard error; OR, odds ratio; ER, estrogen receptor; PR, progesterone receptor.

ZakiSMAbdel-AzeezHAEl NagarMRMetwallyKAS AhmeedMMAnalysis of FHIT gene methylation in egyptian breast cancer women: association with clinicopathological featuresAsian Pac J Cancer Prev20151631235123925735361

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SyeedNHusainSASameerASChowdhriNASiddiqiMAMutational and promoter hypermethylation status of FHIT gene in breast cancer patients of KashmirMutat Res20117071–21821095196

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RaishMDhillonVSAhmadAPromoter Hypermethylation in Tumor Suppressing Genes p16 and FHIT and Their Relationship with Estrogen Receptor and Progesterone Receptor Status in Breast Cancer Patients from Northern IndiaTransl Oncol20092426427019956388

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NaqviRAHussainARaishMSpecific 50′CpG island methylation signatures of FHIT and p16 genes and their potential diagnostic relevance in Indian breast cancer patientsDNA Cell Biol200827951752518593338

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D ZhaoLJLiuGLiSShenABreast fragile histidine triad abnormal methylation can down-regulate the expression of its mRNA and proteinChinese Journal of Breast Disease2012 Accessed from: http://www.cqvip.com/qk/88763x/201201/41530095.html

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IliopoulosDGulerGHanSYFragile genes as biomarkers: epigenetic control of WWOX and FHIT in lung, breast and bladder cancerOncogene20052491625163315674328

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YangQNakamuraMNakamuraYTwo-hit inactivation of FHIT by loss of heterozygosity and hypermethylation in breast cancerClin Cancer Res2002892890289312231533

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