Hormonal and reproductive factors and risk of esophageal cancer in women: a meta-analysis

Wang, B. J.; Zhang, Bin; Yan, Shushan; Li, Z. C.; Jiang, Tao; Hua, C.; Lü, Lei; Liu, X. Z.; Zhang, D. H.; Zhang, R. S.; Wang, X.

doi:10.1111/dote.12349

Cited by 37 publications

(32 citation statements)

References 30 publications

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“…Although some studies failed to show a significant impact of estrogen on pancreatic 20 or bladder cancers, 21 the preventive effect of estrogen against liver cancer in the current study and in others studies was observed for gastric 22 distal large bowel cancer 23 , and esophageal cancers 24 , with an average risk reduction of 28%, and the estimated ORs (95% CI) were .77 (.64–.92) and .68 (.48–.97), respectively. In contrast, estrogen use was significantly associated with increased risk of breast cancer.…”

Section: Discussioncontrasting

confidence: 57%

Estrogen Replacement Reduces Risk and Increases Survival Times of Women With Hepatocellular Carcinoma

Hassan

Botrus

Abdel-Wahab

et al. 2017

Clinical Gastroenterology and Hepatology

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Background & Aims Environmental factors have been identified that affect risk of hepatocellular carcinoma (HCC), but little is known about the effects of sex hormones on liver cancer development or outcome. We investigated whether menopause hormone therapy (MHT) affects risk, age at onset, or outcome of HCC. Methods We performed a case–control study of 234 female patients treated for HCC at a tertiary medical center and with 282 healthy women (controls), from January 1, 2004 through May 31, 2015. We collected detailed information on environmental exposures, ages of menarche and menopause, hysterectomies, and uses of birth control and MHT. We performed multivariable logistic and Cox regression analyses to determine the independent effects of factors associated with women on risk and clinical outcome in HCC. The primary outcomes were effect of MHT on HCC risk, the relationship between MHT with hepatitis virus infection on HCC development, and effect of MHT on age at HCC onset or survival after diagnosis of HCC. Results The estimated adjusted odds ratio (AOR) for HCC in women who ever used estrogen was 0.53 (95% CI, 0.32–0.88). This association was supported by the older age of HCC onset among estrogen users (mean, 64.5±0.9 years) vs non-users (mean, 59.2±1.1 years) (P=.001) and the reduced risk of HCC among long-term users (more than 5 years) (AOR, 0.36; 95% CI, 0.20– 0.63). Users of estrogen also had a reduced risk for hepatitis-associated HCC: AOR for users, 4.37 (95% CI, 1.67–11.44) vs AOR for non-users, 17.60 (95% CI, 3.88–79.83). Estrogen use reduced risk of death from HCC (hazard ratio, 0.55; 95% CI, 0.40–0.77) (P=.01). Median overall survival times were 33.5 months for estrogen users (95% CI, 25.7–41.3 months) and 24.1 months for non-users (95% CI, 19.02–29.30 months) (P=.008). Conclusion In a case–control study of women with HCC vs female controls at a single center, we associated use of estrogen MHT with reduced risk of HCC and increased overall survival times of patients with HCC. Further studies are needed to determine the benefits of estrogen therapy for women and patients with HCC, and effects of tumor expression of estrogen receptor.

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Section: Discussioncontrasting

confidence: 57%

Estrogen Replacement Reduces Risk and Increases Survival Times of Women With Hepatocellular Carcinoma

Hassan

Botrus

Abdel-Wahab

et al. 2017

Clinical Gastroenterology and Hepatology

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“…However, an inverse association was observed between parity and EA. A meta‐analysis by Wang et al . reported no association for EA with reproductive factors; however, this analysis did show an inverse association between breastfeeding and EA .…”

Section: Discussioncontrasting

confidence: 55%

“…A meta‐analysis by Wang et al . reported no association for EA with reproductive factors; however, this analysis did show an inverse association between breastfeeding and EA . A recent meta‐analysis reported an inverse association between breastfeeding, parity and esophageal cancer…”

Section: Discussionmentioning

confidence: 83%

“…It has been suggested that female sex hormones, particularly estrogens, may protect against the development of esophageal and gastric cancer. 19,20 Some epidemiological studies have investigated the role of hormonal and reproductive factors in the development of esophageal and gastric cancer risk [21][22][23][24] ; however, prospective studies examining these relationships by subtype of esophageal cancer and subsite of gastric cancer are limited, with conflicting results. [25][26][27][28][29] The association between reproductive factors and gastric cancer was investigated in a previous analysis of the EPIC cohort, which included participants with follow-up through 2004; this analysis showed a positive association between ovariectomy and gastric cancer risk.…”

Section: Introductionmentioning

confidence: 99%

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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

Muller

Sophiea

et al. 2019

Intl Journal of Cancer

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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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“…The systematic epidemiological studies suggest that BRCA1 and BRCA2 are important susceptibility genes of familial breast cancer [2–6]; however, population and hospital-based studies indicate that mutations in these two genes account for only 4–6% of total breast cancer cases [7, 8]. Other susceptibility factors that contribute to breast cancer have been identified as being related to exposure to environmental carcinogens (including certain chemicals and ionizing radiation), as well as increasing age, family and reproductive history, obesity, heavy alcohol intake and hormonal replacement therapy [9–19]. There is considerable inter-individual variation in their susceptibility to environmental carcinogens.…”

Section: Introductionmentioning

confidence: 99%

Interaction between APC and Fen1 during breast carcinogenesis

et al. 2016

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Aberrant DNA base excision repair (BER) contributes to malignant transformation. However, inter-individual variations in DNA repair capacity plays a key role in modifying breast cancer risk. We review here emerging evidence that two proteins involved in BER – adenomatous polyposis coli (APC) and flap endonuclease 1 (Fen1) – promote the development of breast cancer through novel mechanisms. APC and Fen1 expression and interaction is increased in breast tumors versus normal cells, APC interacts with and blocks Fen1 activity in Pol-β-directed LP-BER, and abrogation of LP-BER is linked with cigarette smoke condensate-induced transformation of normal breast epithelial cells. Carcinogens increase expression of APC and Fen1 in spontaneously immortalized human breast epithelial cells, human colon cancer cells, and mouse embryonic fibroblasts. Since APC and Fen1 are tumor suppressors, an increase in their levels could protect against carcinogenesis; however, this does not seem to be the case. Elevated Fen1 levels in breast and lung cancer cells may reflect the enhanced proliferation of cancer cells or increased DNA damage in cancer cells compared to normal cells. Inactivation of the tumor suppressor functions of APC and Fen1 is due to their interaction, which may act as a susceptibility factor for breast cancer. The increased interaction of APC and Fen1 may occur due to polypmorphic and/or mutational variation in these genes. Screening of APC and Fen1 polymorphic and/or mutational variations and APC/Fen1 interaction may permit assessment of individual DNA repair capability and the risk for breast cancer development. Such individuals might lower their breast cancer risk by reducing exposure to carcinogens. Stratifying individuals according to susceptibility would greatly assist epidemiologic studies of the impact of suspected environmental carcinogens. Additionally, a mechanistic understanding of the interaction of APC and Fen1 may provide the basis for developing new and effective targeted chemopreventive and chemotherapeutic agents.

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Hormonal and reproductive factors and risk of esophageal cancer in women: a meta-analysis

Cited by 37 publications

References 30 publications

Estrogen Replacement Reduces Risk and Increases Survival Times of Women With Hepatocellular Carcinoma

Estrogen Replacement Reduces Risk and Increases Survival Times of Women With Hepatocellular Carcinoma

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

Interaction between APC and Fen1 during breast carcinogenesis

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