PONE-D-22-23624Risk association of RANKL and OPG gene polymorphism with breast cancer to bone metastasis in Pashtun population of Khyber Pakhtunkhwa, PakistanPLOS ONE

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Reviewer #1: Yes

Reviewer #2: Partly

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: Yes

Reviewer #2: Yes

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Reviewer #1: The authors analyze the receptor activator NF-κB ligand (RANKL) and Osteoprotegrin (OPG). The single nucleotide polymorphisms (SNPs) of OPG (rs3102735) and RANKL (rs9533156) exhibited significant association with the risk of breast cancer to bone metastasis in Pashtun populationof Khyber Pakhtunkhwa, Pakistan.

Genetic factors may predispose the probability of breast cancer metastasize to bone.

RANKL-OPG pathway contributes to the primary tumorigenesis and bone metastasis and may be used as a potential prognostic biomarker for breast cancers, in Pashtun population. These conclusions appear to be supported by the results of the present analysis, limited to the population in question.

Reviewer #2: In the manuscript “Risk association of RANKL and OPG gene polymorphism with breast cancer to bone

metastasis in Pashtun population of Khyber Pakhtunkhwa, Pakistan” the authors have associated OPG (rs3102735) and RANKL (rs9533156) polymorphisms with the risk of breast-to-bone metastasis in the Pashtun population.

I recommend accepting this work with Minor revision.

The manuscript is relatively well designed and written despite the group enrolled for the analysis being too small. The statistical analysis was been appropriately performed.

I suggest to the authors some Minor Revisions:

Did you hypotize the relationship between these polymorphisms and the Pashtun population?

Did you evaluate the immune response of patients enrolled and the polymorphisms found? What about the HLA haplotype in these patients? I recommend you this work about bone tumors “ doi:10.3390/

Did you evaluate also the protein expression of RANKL and OPG?

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Reviewer #1: No

Reviewer #2: No

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Risk association of RANKL and OPG gene polymorphism with breast cancer to bone metastasis in Pashtun population of Khyber Pakhtunkhwa, Pakistan

PONE-D-22-23624R1

Dear Dr.Khan

We’re pleased to inform you that your manuscript has been judged scientifically suitable for publication and will be formally accepted for publication once it meets all outstanding technical requirements.

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Kind regards,

Filomena de Nigris, Ph.D.

Academic Editor

PLOS ONE