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Reproductive factors and risk of esophageal squamous cell carcinoma in northern Iran: a case-control study in a high-risk area and literature review.

ABSTRACT: Several epidemiologic studies have suggested an inverse association between female reproductive factors and the risk of esophageal squamous cell carcinoma (ESCC), but the evidence is not conclusive. We examined the association of the number of pregnancies, live births, and miscarriages/stillbirths in women and the association of the number of children in both sexes with the risk of ESCC in Golestan Province, a high-risk area in Iran. Data from 297 histopathologically confirmed ESCC cases (149 women) and 568 controls (290 women) individually matched to cases for age, sex, and neighborhood of residence were included in this analysis. Conditional logistic regression was used to calculate odds ratios (ORs) and the corresponding 95% confidence intervals (CIs). The average numbers of live births and miscarriages/stillbirths among the controls were 8.2 and 0.8, respectively. Women with six or more live births were at ~1/3 the risk of ESCC as those with 0-3 live births; the OR (95% CI) for having 6-7 live births was 0.33 (0.12-0.92). In contrast, the number of miscarriages/stillbirths was associated with an increase in the risk of ESCC. The OR (95% CI) for at least three versus no miscarriages/stillbirths was 4.43 (2.11-9.33). The number of children in women was suggestive of an inverse association with ESCC, but this association was not statistically significant; in men, no association was observed. The findings of this study support a protective influence of female hormonal factors on the risk of ESCC. However, further epidemiological and mechanistic studies are required to prove a protective association.

SUBMITTER: Islami F

PROVIDER: S-EPMC3731403 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Reproductive factors and risk of esophageal squamous cell carcinoma in northern Iran: a case-control study in a high-risk area and literature review.

Islami Farhad F Cao Yin Y Kamangar Farin F Nasrollahzadeh Dariush D Marjani Haji-Amin HA Shakeri Ramin R Fahimi Saman S Sotoudeh Masoud M Dawsey Sanford M SM Abnet Christian C CC Boffetta Paolo P Malekzadeh Reza R

European journal of cancer prevention : the official journal of the European Cancer Prevention Organisation (ECP) 20130901 5

Several epidemiologic studies have suggested an inverse association between female reproductive factors and the risk of esophageal squamous cell carcinoma (ESCC), but the evidence is not conclusive. We examined the association of the number of pregnancies, live births, and miscarriages/stillbirths in women and the association of the number of children in both sexes with the risk of ESCC in Golestan Province, a high-risk area in Iran. Data from 297 histopathologically confirmed ESCC cases (149 wo ...[more]

PMID: 23238586

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Project description:Although Iran is a high-risk region for esophageal squamous cell carcinoma (ESCC), dietary factors that may contribute to this high incidence have not been thoroughly studied. The aim of this study was to evaluate the effect of macronutrients, vitamins and minerals on the risk of ESCC.In this hospital-based case-control study, 47 cases with incident ESCC and 96 controls were interviewed and usual dietary intakes were collected using a validated food frequency questionnaire. Data were modeled through unconditional multiple logistic regression to estimate odds ratios (OR) and 95% confidence intervals (CI), controlling for age, sex, gastrointestinal reflux, body mass index, smoking history (status, intensity and duration), physical activity, and education.ESCC cases consumed significantly more hot foods and beverages and fried and barbecued meals, compared to the controls (p < 0.05). After adjusting for potential confounders, the risk of ESCC increased significantly in the highest tertiles of saturated fat [OR:2.88,95%CI:1.15-3.08], cholesterol [OR:1.53, 95%CI: 1.41-4.13], discretionary calorie [OR:1.51, 95%CI: 1.06-3.84], sodium [OR:1.49,95%CI:1.12-2.89] and total fat intakes [OR:1.48, 95%CI:1.09-3.04]. In contrast, being in the highest tertile of carbohydrate, dietary fiber and (n-3) fatty acid intake reduced the ESCC risk by 78%, 71% and 68%, respectively. The most cancer-protective effect was observed for the combination of high folate and vitamin E intakes (OR: 0.02, 95%CI: 0.00-0.87; p < 0.001). Controls consumed 623.5 times higher selenium, 5.48 times as much β-carotene and 1.98 times as much α-tocopherol as the amount ESCC cases consumed.This study suggests that high intake of nutrients primarily found in plant-based foods is associated with a reduced esophageal cancer risk. Some nutrients such as folate, vitamin E and selenium might play major roles in the etiology of ESCC and their status may eventually be used as an epidemiological marker for esophageal cancer in Iran, and perhaps other high-risk regions.

Project description:BackgroundThe human major histocompatibility complex (MHC) is the most important region in vertebrate genome, and is crucial in innate immunity. Recent studies have demonstrated the possible role of polymorphisms in the MHC region to high risk for esophageal squamous cell carcinoma (ESCC). Our previous genome-wide association study (GWAS) has indicated that the MHC region may confer important risk loci for ESCC, but without further fine mapping. The aim of this study is to further identify the risk loci in the MHC region for ESCC in Chinese population.MethodsConditional logistic regression analysis (CLRA) was performed on 24 single nucleotide polymorphisms (SNPs) within the MHC region, which were obtained from the genetically matched 937 cases and 692 controls of Chinese Han population. The identified promising SNPs were further correlated with clinical and clinicopathology characteristics. Immunohistochemistry was performed to explore the protein expression pattern of the related genes in ESCC and neighboring normal tissues.ResultsOf the 24 promising SNPs analyzed, we identified three independent SNPs in the MHC region associated with ESCC: rs35399661 (P = 6.07E-06, OR = 1.71, 95%CI = 1.36-2.17), rs3763338 (P = 1.62E-05, OR = 0.63, 95%CI = 0.50-0.78) and rs2844695 (P = 7.60E-05, OR = 0.74, 95%CI = 0.64-0.86). These three SNPs were located at the genes of HLA-DQA1, TRIM27, and DPCR1, respectively. Further analyses showed that rs2844695 was preferentially associated with younger ESCC cases (P = 0.009). The positive immunostaining rates both for HLA-DQA1 and TRIM27 were much higher in ESCC tissues than in neighboring normal tissues (69.4% vs. 26.8% for HLA-DQA1 and 77.6% vs. 47.8% for TRIM27, P<0.001). Furthermore, the overexpression of HLA-DQA1 is correlated significantly with age (P = 0.001) and family history (P<0.001).ConclusionThis study for the first time provides evidence that multiple genetic factors within the MHC region confer risk to ESCC on the subjects from high-risk area in northern China.

Dataset Information

Reproductive factors and risk of esophageal squamous cell carcinoma in northern Iran: a case-control study in a high-risk area and literature review.

Publications

Reproductive factors and risk of esophageal squamous cell carcinoma in northern Iran: a case-control study in a high-risk area and literature review.

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