Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

Harinakshi Sanikini, David C. Muller, Marisa Sophiea, Sabina Rinaldi, Antonio Agudo, Eric J. Duell, Elisabete Weiderpass, Kim Overvad, Anne Tjønneland, Jytte Halkjær, Marie Christine Boutron-Ruault, Franck Carbonnel, Iris Cervenka, Heiner Boeing, Rudolf Kaaks, Tilman Kühn, Antonia Trichopoulou, Georgia Martimianaki, Anna Karakatsani, Valeria PalaDomenico Palli, Amalia Mattiello, Rosario Tumino, Carlotta Sacerdote, Guri Skeie, Charlotta Rylander, María Dolores Chirlaque López, Maria Jose Sánchez, Eva Ardanaz, Sara Regnér, Tanja Stocks, Bas Bueno-de-Mesquita, Roel C.H. Vermeulen, Dagfinn Aune, Tammy Y.N. Tong, Nathalie Kliemann, Neil Murphy, Marc Chadeau-Hyam, Marc J. Gunter, Amanda J. Cross

Research output: Contribution to journalArticle

Abstract

Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.

Original languageEnglish
JournalInternational Journal of Cancer
DOIs
Publication statusAccepted/In press - Jan 1 2019

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Esophageal Neoplasms
Stomach Neoplasms
Confidence Intervals
Waist-Hip Ratio
Neoplasms
Stomach
Adenocarcinoma
Body Mass Index
Gastrointestinal Neoplasms
Obesity
Cardia
Waist Circumference
Ovariectomy
Proportional Hazards Models
Pregnancy

Keywords

  • cancer
  • esophageal
  • gastric
  • hormones
  • obesity
  • reproductive

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite : Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. / Sanikini, Harinakshi; Muller, David C.; Sophiea, Marisa; Rinaldi, Sabina; Agudo, Antonio; Duell, Eric J.; Weiderpass, Elisabete; Overvad, Kim; Tjønneland, Anne; Halkjær, Jytte; Boutron-Ruault, Marie Christine; Carbonnel, Franck; Cervenka, Iris; Boeing, Heiner; Kaaks, Rudolf; Kühn, Tilman; Trichopoulou, Antonia; Martimianaki, Georgia; Karakatsani, Anna; Pala, Valeria; Palli, Domenico; Mattiello, Amalia; Tumino, Rosario; Sacerdote, Carlotta; Skeie, Guri; Rylander, Charlotta; Chirlaque López, María Dolores; Sánchez, Maria Jose; Ardanaz, Eva; Regnér, Sara; Stocks, Tanja; Bueno-de-Mesquita, Bas; Vermeulen, Roel C.H.; Aune, Dagfinn; Tong, Tammy Y.N.; Kliemann, Nathalie; Murphy, Neil; Chadeau-Hyam, Marc; Gunter, Marc J.; Cross, Amanda J.

In: International Journal of Cancer, 01.01.2019.

Research output: Contribution to journalArticle

Sanikini, H, Muller, DC, Sophiea, M, Rinaldi, S, Agudo, A, Duell, EJ, Weiderpass, E, Overvad, K, Tjønneland, A, Halkjær, J, Boutron-Ruault, MC, Carbonnel, F, Cervenka, I, Boeing, H, Kaaks, R, Kühn, T, Trichopoulou, A, Martimianaki, G, Karakatsani, A, Pala, V, Palli, D, Mattiello, A, Tumino, R, Sacerdote, C, Skeie, G, Rylander, C, Chirlaque López, MD, Sánchez, MJ, Ardanaz, E, Regnér, S, Stocks, T, Bueno-de-Mesquita, B, Vermeulen, RCH, Aune, D, Tong, TYN, Kliemann, N, Murphy, N, Chadeau-Hyam, M, Gunter, MJ & Cross, AJ 2019, 'Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite: Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort', International Journal of Cancer. https://doi.org/10.1002/ijc.32386
Sanikini, Harinakshi ; Muller, David C. ; Sophiea, Marisa ; Rinaldi, Sabina ; Agudo, Antonio ; Duell, Eric J. ; Weiderpass, Elisabete ; Overvad, Kim ; Tjønneland, Anne ; Halkjær, Jytte ; Boutron-Ruault, Marie Christine ; Carbonnel, Franck ; Cervenka, Iris ; Boeing, Heiner ; Kaaks, Rudolf ; Kühn, Tilman ; Trichopoulou, Antonia ; Martimianaki, Georgia ; Karakatsani, Anna ; Pala, Valeria ; Palli, Domenico ; Mattiello, Amalia ; Tumino, Rosario ; Sacerdote, Carlotta ; Skeie, Guri ; Rylander, Charlotta ; Chirlaque López, María Dolores ; Sánchez, Maria Jose ; Ardanaz, Eva ; Regnér, Sara ; Stocks, Tanja ; Bueno-de-Mesquita, Bas ; Vermeulen, Roel C.H. ; Aune, Dagfinn ; Tong, Tammy Y.N. ; Kliemann, Nathalie ; Murphy, Neil ; Chadeau-Hyam, Marc ; Gunter, Marc J. ; Cross, Amanda J. / Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite : Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort. In: International Journal of Cancer. 2019.
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abstract = "Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95{\%} confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95{\%} CI: 1.25–3.03) and women (HR = 2.66, 95{\%} CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95{\%} CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95{\%} CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95{\%} CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95{\%} CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95{\%} CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95{\%} CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95{\%} CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.",
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T1 - Anthropometric and reproductive factors and risk of esophageal and gastric cancer by subtype and subsite

T2 - Results from the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort

AU - Sanikini, Harinakshi

AU - Muller, David C.

AU - Sophiea, Marisa

AU - Rinaldi, Sabina

AU - Agudo, Antonio

AU - Duell, Eric J.

AU - Weiderpass, Elisabete

AU - Overvad, Kim

AU - Tjønneland, Anne

AU - Halkjær, Jytte

AU - Boutron-Ruault, Marie Christine

AU - Carbonnel, Franck

AU - Cervenka, Iris

AU - Boeing, Heiner

AU - Kaaks, Rudolf

AU - Kühn, Tilman

AU - Trichopoulou, Antonia

AU - Martimianaki, Georgia

AU - Karakatsani, Anna

AU - Pala, Valeria

AU - Palli, Domenico

AU - Mattiello, Amalia

AU - Tumino, Rosario

AU - Sacerdote, Carlotta

AU - Skeie, Guri

AU - Rylander, Charlotta

AU - Chirlaque López, María Dolores

AU - Sánchez, Maria Jose

AU - Ardanaz, Eva

AU - Regnér, Sara

AU - Stocks, Tanja

AU - Bueno-de-Mesquita, Bas

AU - Vermeulen, Roel C.H.

AU - Aune, Dagfinn

AU - Tong, Tammy Y.N.

AU - Kliemann, Nathalie

AU - Murphy, Neil

AU - Chadeau-Hyam, Marc

AU - Gunter, Marc J.

AU - Cross, Amanda J.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.

AB - Obesity has been associated with upper gastrointestinal cancers; however, there are limited prospective data on associations by subtype/subsite. Obesity can impact hormonal factors, which have been hypothesized to play a role in these cancers. We investigated anthropometric and reproductive factors in relation to esophageal and gastric cancer by subtype and subsite for 476,160 participants from the European Prospective Investigation into Cancer and Nutrition cohort. Multivariable hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated using Cox models. During a mean follow-up of 14 years, 220 esophageal adenocarcinomas (EA), 195 esophageal squamous cell carcinomas, 243 gastric cardia (GC) and 373 gastric noncardia (GNC) cancers were diagnosed. Body mass index (BMI) was associated with EA in men (BMI ≥30 vs. 18.5–25 kg/m2: HR = 1.94, 95% CI: 1.25–3.03) and women (HR = 2.66, 95% CI: 1.15–6.19); however, adjustment for waist-to-hip ratio (WHR) attenuated these associations. After mutual adjustment for BMI and HC, respectively, WHR and waist circumference (WC) were associated with EA in men (HR = 3.47, 95% CI: 1.99–6.06 for WHR >0.96 vs. <0.91; HR = 2.67, 95% CI: 1.52–4.72 for WC >98 vs. <90 cm) and women (HR = 4.40, 95% CI: 1.35–14.33 for WHR >0.82 vs. <0.76; HR = 5.67, 95% CI: 1.76–18.26 for WC >84 vs. <74 cm). WHR was also positively associated with GC in women, and WC was positively associated with GC in men. Inverse associations were observed between parity and EA (HR = 0.38, 95% CI: 0.14–0.99; >2 vs. 0) and age at first pregnancy and GNC (HR = 0.54, 95% CI: 0.32–0.91; >26 vs. <22 years); whereas bilateral ovariectomy was positively associated with GNC (HR = 1.87, 95% CI: 1.04–3.36). These findings support a role for hormonal pathways in upper gastrointestinal cancers.

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