No Evidence of Gene–Calcium Interactions from Genome-Wide Analysis of Colorectal Cancer Risk

Mengmeng Du; Xuehong Zhang; Michael Hoffmeister; Robert E. Schoen; John A. Baron; Sonja I. Berndt; Hermann Brenner; Christopher S. Carlson; Graham Casey; Andrew T. Chan; Keith R. Curtis; David Duggan; W. James Gauderman; Edward L. Giovannucci; Jian Gong; Tabitha A. Harrison; Richard B. Hayes; Brian E. Henderson; John L. Hopper; Li Hsu; Thomas J. Hudson; Carolyn M. Hutter; Mark A. Jenkins; Shuo Jiao; Jonathan M. Kocarnik; Laurence N. Kolonel; Loic Le Marchand; Yi Lin; Polly A. Newcomb; Anja Rudolph; Daniela Seminara; Mark D. Thornquist; Cornelia M. Ulrich; Emily White; Kana Wu; Brent W. Zanke; Peter T. Campbell; Martha L. Slattery; Ulrike Peters; Jenny Chang-Claude; John D. Potter

doi:10.1158/1055-9965.EPI-14-0893

DOI: 10.1158/1055-9965.EPI-14-0893 Published December 2014

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Figure 1.
Association between calcium intake and risk of colorectal cancer. Odds ratios (ORs) and 95% confidence intervals correspond to each quartile increase in A) total calcium intake (mg/d), B) dietary calcium intake (mg/d), and C) supplemental calcium intake (≥500 versus <500 mg/d). Total and dietary calcium intake were coded as sex- and study-specific quartiles based on cutoff points in controls, and modeled as an ordinal variable. Estimates adjusted for age (continuous), sex (F/M), study center (indicators), and energy consumption (continuous). CC, case–control; lower/upper, lower and upper bounds of 95% CI.

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Table 1.

SNP with smallest P for interaction with total, dietary, or supplemental calcium for colorectal cancer risk

										Interaction results^b^,^c
Calcium analysis	SNP with smallest P for interaction	Locus	Position (bp)^a	Function class	Genetic region	Minor allele	Alt allele	MAF	Mean Rsq	Variable	OR-int (95% CI)	P	P_het
Total	rs1933755	6q23.1	130925767	Intergenic	TMEM200A/EPB41L2	C	T	0.10	0.93	Total	0.84 (0.78–0.90)	1.5E−06	4.1E−01
										Dietary	0.86 (0.80–0.92)	5.2E−05	3.2E−01
										Suppl	0.81 (0.65–1.02)	7.4E−02	5.5E−01
Dietary	rs6855885	4q22.1	92039007	Intronic	FAM190A	A	G	0.50	0.94	Total	1.09 (1.04–1.13)	9.0E−05	2.5E−01
										Dietary	1.11 (1.06–1.16)	1.9E−06	5.5E−01
										Suppl	0.93 (0.81–1.07)	3.0E−01	2.4E−01
Supplemental	rs1028166	4q34.3	182813298	Intergenic	AGA/TENM3	G	A	0.31	0.85	Total	1.07 (1.02–1.12)	6.7E−03	3.8E−01
										Dietary	1.02 (0.97–1.07)	5.2E−01	7.4E−01
										Suppl	1.49 (1.27–1.74)	7.3E−07	2.9E−01

Abbreviations: Alt, alternate; MAF, minor allele frequency; OR-int, odds ratio for interaction; P_het, P for heterogeneity across studies; Rsq, imputation Rsq.

↵^aOn the basis of NCBI build 37 data.
↵^bCorresponds to each additional copy of the minor allele (i.e., assuming additive genetic effects) and each quartile increase in calcium intake (total, dietary) or ≥500 versus <500 mg/d (supplemental). Genotyped SNPs were modeled as 0, 1, or 2 copies of the minor allele; imputed SNPs were modeled as the expected number of copies of the minor allele (the genotype “dosage”; refs. 3, 7).
↵^cOn the basis of multivariable logistic regression adjusted for age (continuous), sex (F/M), study center (indicators), energy consumption (continuous), first 3 principal components of genetic ancestry (continuous), SNP main effect, and calcium main effect.