Relative risks (RR) between selected risk factors and esophageal cancer, used in the calculation of Population Attributable Fractions.

*<p>Our estimates of RRs were obtained from a meta-analysis and were first transformed into a log scale and divided by 100 to get the log RR/gram per day, and then multiplied by the lower limit of every quintile of vegetable or fruit consumption. Finally, we divided the RRs in the other quintiles by that in quintile 5 (Q5) to obtain final estimates, and we assumed that the RR in Q5 was equal to 1. The details of this RR calculation for low vegetable and fruit intake have been described elsewhere <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042281#pone.0042281-Xiao1" target="_blank">[15]</a>.</p

Comparison of relative risk, prevalence and population attributable fraction (PAF) for smoking and esophageal cancer in three studies from China.

*<p>Smoking prevalence was calculated from relative risk and PAF.</p>†<p>Smoking prevalence came from the international collaborative study of cardiovascular disease in Asia <a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0042281#pone.0042281-Gu2" target="_blank">[29]</a>.</p>‡<p>PAF was estimated using the following formula: .</p

Esophageal cancer deaths and cases attributable to smoking, drinking, low vegetable intake and low fruit intake in China in 2005.

*<p>Combined PAF for smoking, drinking, low vegetable intake and low fruit intake and esophageal cancer was calculated using the following formula: PAF = 1−(1−PAF₁)×(1−PAF₂)×(1−PAF₃)×(1−PAF₄).</p>†<p>PAF = Population Attributable Fraction.</p

BMI and other breast cancer risk factors among pre- and post-menopausal cases.

<p>BMI = body mass index;</p>a<p>Test for heterogeneity in all, pre-, and post-menopausal cases respectively.</p

BMI and pathological characteristics of breast cancer among pre- and post-menopausal cases.

<p>BMI = body mass index; CIS = carcinoma in situ; IDC = invasive ductal carcinoma; LNM = lymph mode metastasis;</p><p>ER = estrogen receptor; PR = progesterone receptor; HER2 = human epidermal growth factor type 2 receptor;</p>a<p>Test for heterogeneity in all, pre-, and post-menopausal cases respectively.</p

Genetic Variants in Epidermal Growth Factor Receptor Pathway Genes and Risk of Esophageal Squamous Cell Carcinoma and Gastric Cancer in a Chinese Population

<div><p>The epidermal growth factor receptor (EGFR) signaling pathway regulates cell proliferation, differentiation, and survival, and is frequently dysregulated in esophageal and gastric cancers. Few studies have comprehensively examined the association between germline genetic variants in the EGFR pathway and risk of esophageal and gastric cancers. Based on a genome-wide association study in a Han Chinese population, we examined 3443 SNPs in 127 genes in the EGFR pathway for 1942 esophageal squamous cell carcinomas (ESCCs), 1758 gastric cancers (GCs), and 2111 controls. SNP-level analyses were conducted using logistic regression models. We applied the resampling-based adaptive rank truncated product approach to determine the gene- and pathway-level associations. The EGFR pathway was significantly associated with GC risk (<i>P</i> = 2.16×10⁻³). Gene-level analyses found 10 genes to be associated with GC, including <i>FYN</i>, <i>MAPK8</i>, <i>MAP2K4</i>, <i>GNAI3</i>, <i>MAP2K1</i>, <i>TLN1</i>, <i>PRLR</i>, <i>PLCG2</i>, <i>RPS6KB2</i>, and <i>PIK3R3</i> (<i>P</i><0.05). For ESCC, we did not observe a significant pathway-level association (<i>P</i> = 0.72), but gene-level analyses suggested associations between <i>GNAI3</i>, <i>CHRNE</i>, <i>PAK4</i>, <i>WASL</i>, and <i>ITCH</i>, and ESCC (<i>P</i><0.05). Our data suggest an association between specific genes in the EGFR signaling pathway and risk of GC and ESCC. Further studies are warranted to validate these associations and to investigate underlying mechanisms.</p></div

Baseline characteristics stratified by availability of BMI results.

<p>BMI = body mass index; SD = standard deviance.</p>a<p>Test for heterogeneity between BMI obtained group and BMI missing group.</p

Epidermal growth factor receptor pathway genes significantly associated with risk of esophageal squamous cell carcinoma^*.

<p>Abbreviations: MAF, minor allele frequency; OR, odds ratio; SNP, single nucleotide polymorphism.</p>*<p>Genes with <i>P</i>-value <0.05 are listed and ordered by <i>P</i>-values. Gene-level <i>P-</i>values were calculated using the adaptive rank truncated product approach. The <i>P</i>-values and ORs for the SNPs were calculated from unconditional logistic regression models using genotype trend tests adjusted for age (10-year categories), sex and study.</p

Top SNPs associated with risk of esophageal squamous cell carcinoma (ESCC) and gastric cancer (GC)^a.

<p>Abbreviations: CI, confidence interval; ESCC, esophageal squamous cell carcinoma; GC, gastric cancer; MAF, minor allele frequency; OR, odds ratio; SNP, single nucleotide polymorphism.</p>a<p>All SNPs with <i>P</i>-value <0.002 for esophageal squamous cell carcinoma (ESCC), gastric cancer (GC) overall or by anatomic sites are listed. The top SNPs for total GC (<i>P</i>-value <0.002) which have <i>P</i>-value <0.05 for cardia or noncardia cancer are also listed. Results were derived from logistic regression models using genotype trend tests adjusted for age (10-year categories), sex and study.</p>b<p>These SNPs were significant only for gastric cardia or noncardia cancer, but not for total gastric cancer.</p