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. 2024 Sep 3;33(9):1229-1239.
doi: 10.1158/1055-9965.EPI-24-0096.

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

Zhanmo Ni  1 , Prosenjit Kundu  2 , David F McKean  1 , William Wheeler  3 , Demetrius Albanes  4 , Gabriella Andreotti  5 , Samuel O Antwi  6 , Alan A Arslan  7   8   9 , William R Bamlet  10 , Laura E Beane-Freeman  5 , Sonja I Berndt  5 , Paige M Bracci  11 , Paul Brennan  12 , Julie E Buring  13   14 , Stephen J Chanock  5 , Steven Gallinger  15 , J M Gaziano  13   16   17 , Graham G Giles  18   19   20 , Edward L Giovannucci  21 , Michael G Goggins  22 , Phyllis J Goodman  23 , Christopher A Haiman  24 , Manal M Hassan  25 , Elizabeth A Holly  11 , Rayjean J Hung  15 , Verena Katzke  26 , Charles Kooperberg  27 , Peter Kraft  28 , Loic LeMarchand  29 , Donghui Li  25 , Marjorie L McCullough  30 , Roger L Milne  18   19   20 , Steven C Moore  4 , Rachel E Neale  31 , Ann L Oberg  10 , Alpa V Patel  30 , Ulrike Peters  32 , Kari G Rabe  10 , Harvey A Risch  33 , Xiao-Ou Shu  34 , Karl Smith-Byrne  35 , Kala Visvanathan  36 , Jean Wactawski-Wende  37 , Emily White  32   38 , Brian M Wolpin  21 , Herbert Yu  39 , Anne Zeleniuch-Jacquotte  8   40 , Wei Zheng  34 , Jun Zhong  41 , Laufey T Amundadottir  41 , Rachael Z Stolzenberg-Solomon #  4 , Alison P Klein #  1   22   36
Affiliations

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

Zhanmo Ni et al. Cancer Epidemiol Biomarkers Prev. .

Abstract

Background: Pancreatic cancer is a leading cause of cancer-related death globally. Risk factors for pancreatic cancer include common genetic variants and potentially heavy alcohol consumption. We assessed if genetic variants modify the association between heavy alcohol consumption and pancreatic cancer risk.

Methods: We conducted a genome-wide interaction analysis of single-nucleotide polymorphisms (SNP) by heavy alcohol consumption (more than three drinks per day) for pancreatic cancer in European ancestry populations from genome-wide association studies. Our analysis included 3,707 cases and 4,167 controls from case-control studies and 1,098 cases and 1,162 controls from cohort studies. Fixed-effect meta-analyses were conducted.

Results: A potential novel region of association on 10p11.22, lead SNP rs7898449 (interaction P value (Pinteraction) = 5.1 × 10-8 in the meta-analysis; Pinteraction = 2.1 × 10-9 in the case-control studies; Pinteraction = 0.91 in the cohort studies), was identified. An SNP correlated with this lead SNP is an expression quantitative trait locus for the neuropilin 1 gene. Of the 17 genomic regions with genome-wide significant evidence of association with pancreatic cancer in prior studies, we observed suggestive evidence that heavy alcohol consumption modified the association for one SNP near LINC00673, rs11655237 on 17q25.1 (Pinteraction = 0.004).

Conclusions: We identified a novel genomic region that may be associated with pancreatic cancer risk in conjunction with heavy alcohol consumption located near an expression quantitative trait locus for neuropilin 1, a protein that plays an important role in the development and progression of pancreatic cancer.

Impact: This work can provide insights into the etiology of pancreatic cancer, particularly in heavy drinkers.

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Conflict of interest statement

The authors declare no potential conflicts of interest.

Figures

Figure 1.
Figure 1.. Overview of Study Populations
Overview of Study GWAS phases and meta-analysis.
Figure 2.
Figure 2.. Manhattan Plots of GWAS Results
A. Manhattan Plot of p-values of SNP X Alcohol interaction P-values for Meta-Analysis including PanC4, PanScan I and PanScan II GWAS Phases. B. Manhattan Plot of SNP X Alcohol interaction P-values for Meta-Analysis including Case-Control GWAS Phases (PanC4, PanScan II). C. Manhattan Plot of SNP X Alcohol interaction P-values for PanScan I.
Figure 3.
Figure 3.. Locus Plot of the 10p11.22 Region of Association
Zoomed in locus plot 10p11.22 region for the interaction GWAS of pancreatic cancer by heavy alcohol consumption with meta-analysis with all GWAS phases interaction p-values (SNPs are colored on the basis of r2) and eQTL p-values for the most significant associations (GTEx v8). eQTLs are colored on the basis of tissue types.
See this image and copyright information in PMC

References

    1. Gordon-Dseagu VL, Devesa SS, Goggins M, Stolzenberg-Solomon R. Pancreatic cancer incidence trends: evidence from the Surveillance, Epidemiology and End Results (SEER) population-based data. Int J Epidemiol 2018;47:427–39 - PMC - PubMed
    1. Collaborators GBDPC. The global, regional, and national burden of pancreatic cancer and its attributable risk factors in 195 countries and territories, 1990–2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Gastroenterol Hepatol 2019;4:934–47 - PMC - PubMed
    1. Siegel RL, Miller KD, Wagle NS, Jemal A. Cancer statistics, 2023. CA Cancer J Clin 2023;73:17–48 - PubMed
    1. Zhou C, Porter N, Borges M, Gauthier C, Ferguson L, Huang B, et al. Examination of ATM, BRCA1, and BRCA2 promoter methylation in patients with pancreatic cancer. Pancreatology 2021 - PMC - PubMed
    1. Porter N, Laheru D, Lau B, He J, Zheng L, Narang A, et al. Risk of Pancreatic Cancer in the Long-Term Prospective Follow-Up of Familial Pancreatic Cancer Kindreds. J Natl Cancer Inst 2022 - PMC - PubMed