Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and
MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC
cohort
Version: 2 Date: 12 Jan 2025
Reviewer:  Zhaohui Tang
Reviewer's report:
This paper explores the genetic predisposition of NASH-related HCC in Sri Lanka, focusing
on five known variants in PNPLA3, TM6SF2, and MBOAT7 genes. The study analyzes
tumor characteristics (tumor nodularity, size, AFP levels) and potential biomarkers (leukocyte
telomere length, miR-122 expression) in 48 NASH-HCC patients. Notably, particular PNPLA3
variants (rs2281135, rs2294918) are shown to correlate with tumor nodularity, higher miR-122
expression, and distinct demographic/anthropometric features (e.g., age, BMI). Overall, the
work highlights the importance of specific genetic variants in tumor aggressiveness, contributing
to ongoing discussions on precision screening for HCC in NASH patients.
However#there are still some issues to be addressed before it’s suitable for publication:
1.Could you provide additional details on the power calculation used to determine that 48
patients would be sufficient to detect significant genetic associations?
2.Could you elaborate on whether these strong associations (especially PNPLA3 rs2281135)
persist in other ethnic groups or in a larger, more diverse study cohort?
3.Although the work is significant for Sri Lankan populations, additional insight or discussion
on how these findings might translate to broader or multi-ethnic contexts could strengthen the
paper’s global relevance.
4.Besides age and BMI, are there plans to investigate the impact of other lifestyle and metabolic
risk factors on the identified SNPs and their association with NASH-HCC?
Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and
MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC
cohort
Version: 2 Date: 12 Jan 2025
Reviewer:  Zhaohui Tang
Reviewer's report:
This paper explores the genetic predisposition of NASH-related HCC in Sri Lanka, focusing
on five known variants in PNPLA3, TM6SF2, and MBOAT7 genes. The study analyzes
tumor characteristics (tumor nodularity, size, AFP levels) and potential biomarkers (leukocyte
telomere length, miR-122 expression) in 48 NASH-HCC patients. Notably, particular PNPLA3
variants (rs2281135, rs2294918) are shown to correlate with tumor nodularity, higher miR-122
expression, and distinct demographic/anthropometric features (e.g., age, BMI). Overall, the
work highlights the importance of specific genetic variants in tumor aggressiveness, contributing
to ongoing discussions on precision screening for HCC in NASH patients.
However#there are still some issues to be addressed before it’s suitable for publication:
1.Could you provide additional details on the power calculation used to determine that 48
patients would be sufficient to detect significant genetic associations?
2.Could you elaborate on whether these strong associations (especially PNPLA3 rs2281135)
persist in other ethnic groups or in a larger, more diverse study cohort?
3.Although the work is significant for Sri Lankan populations, additional insight or discussion
on how these findings might translate to broader or multi-ethnic contexts could strengthen the
paper’s global relevance.
4.Besides age and BMI, are there plans to investigate the impact of other lifestyle and metabolic
risk factors on the identified SNPs and their association with NASH-HCC?
Please review this paper.
user
Title: Association between single nucleotide polymorphisms in PNPLA3, TM6SF2 and
MBOAT7 genes and markers of cancer aggressiveness in a Sri Lankan NASH-related HCC
cohort
Version: 2 Date: 12 Jan 2025
Reviewer:  Zhaohui Tang
Reviewer's report:
This paper explores the genetic predisposition of NASH-related HCC in Sri Lanka, focusing
on five known variants in PNPLA3, TM6SF2, and MBOAT7 genes. The study analyzes
tumor characteristics (tumor nodularity, size, AFP levels) and potential biomarkers (leukocyte
telomere length, miR-122 expression) in 48 NASH-HCC patients. Notably, particular PNPLA3
variants (rs2281135, rs2294918) are shown to correlate with tumor nodularity, higher miR-122
expression, and distinct demographic/anthropometric features (e.g., age, BMI). Overall, the
work highlights the importance of specific genetic variants in tumor aggressiveness, contributing
to ongoing discussions on precision screening for HCC in NASH patients.
However#there are still some issues to be addressed before it’s suitable for publication:
1.Could you provide additional details on the power calculation used to determine that 48
patients would be sufficient to detect significant genetic associations?
2.Could you elaborate on whether these strong associations (especially PNPLA3 rs2281135)
persist in other ethnic groups or in a larger, more diverse study cohort?
3.Although the work is significant for Sri Lankan populations, additional insight or discussion
on how these findings might translate to broader or multi-ethnic contexts could strengthen the
paper’s global relevance.
4.Besides age and BMI, are there plans to investigate the impact of other lifestyle and metabolic
risk factors on the identified SNPs and their association with NASH-HCC?
assistant