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Genome-Wide Analysis to Assess if Heavy Alcohol Consumption Modifies the Association between SNPs and Pancreatic

Zhanmo Ni1, Prosenjit Kundu2, David F McKean1

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Cancer Epidemiology, Biomarkers & Prevention : a Publication of the American Association for Cancer Research, Cosponsored by the American Society of Preventive Oncology
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This study investigated how genetic variants interact with heavy alcohol consumption to influence pancreatic cancer risk. A novel genomic region near the neuropilin 1 gene was identified, suggesting a link between genetics, alcohol, and pancreatic cancer.

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Area of Science:

  • Genetics and Genomics
  • Cancer Research
  • Epidemiology

Background:

  • Pancreatic cancer is a major global cause of cancer mortality.
  • Established risk factors include genetic predispositions and heavy alcohol consumption.
  • The interaction between genetic variants and alcohol's effect on pancreatic cancer risk requires further investigation.

Purpose of the Study:

  • To assess whether specific genetic variants modify the association between heavy alcohol consumption and pancreatic cancer risk.
  • To identify novel genetic regions associated with pancreatic cancer in the context of heavy alcohol intake.

Main Methods:

  • Genome-wide interaction analysis of single-nucleotide polymorphisms (SNPs) and heavy alcohol consumption (defined as >3 drinks/day).
  • Analysis included European ancestry populations from case-control and cohort studies, totaling 3,707 cases and 4,167 controls, and 1,098 cases and 1,162 controls, respectively.
  • Fixed-effect meta-analyses were employed to combine results.

Main Results:

  • A novel potential region of association on 10p11.22, with lead SNP rs7898449, showed significant interaction (Pinteraction = 5.1 × 10-8).
  • This lead SNP is correlated with an expression quantitative trait locus for the neuropilin 1 gene.
  • Suggestive evidence indicated that heavy alcohol consumption modified the association for SNP rs11655237 near LINC00673 on 17q25.1 (Pinteraction = 0.004).

Conclusions:

  • A novel genomic region associated with pancreatic cancer risk, in conjunction with heavy alcohol consumption, was identified.
  • This region is located near an expression quantitative trait locus for neuropilin 1, a gene implicated in pancreatic cancer development.
  • Findings offer insights into the etiology of pancreatic cancer, especially in heavy drinkers.