Elsevier

European Journal of Cancer

Volume 46, Issue 13, September 2010, Pages 2473-2478
European Journal of Cancer

Male predominance of upper gastrointestinal adenocarcinoma cannot be explained by differences in tobacco smoking in men versus women

https://doi.org/10.1016/j.ejca.2010.05.005Get rights and content

Abstract

Background

Adenocarcinomas of the upper gastrointestinal tract (UGI) show remarkable male predominance. As smoking is a well-established risk factor, we investigated the role of tobacco smoking in the male predominance of UGI adenocarcinomas in the United States NIH-AARP Diet and Health Study.

Method

A questionnaire was completed by 281,422 men and 186,133 women in 1995–1996 who were followed until 31st December 2003. Incident UGI adenocarcinomas were identified by linkage to state cancer registries. We present age-standardised cancer incidence rates per 100,000-person years and male/female ratios (M/F) calculated from age-adjusted Cox proportional hazards models, both with 95% confidence intervals (CI).

Results

After 2013,142-person years follow-up, 338 adenocarcinomas of the oesophagus, 261 of gastric cardia and 222 of gastric non-cardia occurred in men. In women, 23 tumours of oesophagus, 36 of gastric cardia and 88 of gastric non-cardia occurred in 1351,958-person years follow-up. The age-standardised incidence rate of all adenocarcinoma sites was 40.5 (37.8–43.3) and 11.0 (9.2–12.8) in men and women, respectively. Among smokers, the M/F of all UGI adenocarcinomas was 3.4 (2.7–4.1), with a M/F of 7.3 (4.6–11.7) for tumours in oesophagus, 3.7 (2.5–5.4) for gastric cardia and 1.7 (1.2–2.3) for gastric non-cardia. In non-smokers, M/F ratios were 14.2 (5.1–39.5) for oesophagus, 6.1 (2.6–14.7) for gastric cardia and 1.3 (0.8–2.0) for gastric non-cardia. The overall M/F ratio was 3.0 (2.2–4.3).

Conclusion

The male predominance was similar in smokers and non-smokers for these cancer sites. These results suggest that the male predominance of upper GI adenocarcinomas cannot be explained by differences in smoking histories.

Introduction

Adenocarcinomas of the upper gastrointestinal tract (UGI) show remarkable male predominance that is evident in nearly all populations.1 It is well documented in a number of studies in European countries.2, 3, 4, 5 Male gender is a well-established risk factor for oesophageal adenocarcinoma.6, 7 Male predominance of gastric cancer incidence also is an invariable observation reported from different populations. Global data suggest that the male predominance of upper gastrointestinal cancer is related to the anatomical location, being higher for proximal and lower for distal tumours.8 Recent data suggest that the male predominance is related to the histological type rather than anatomical location. Tumours with intestinal subtype showed similar male predominance of incidence irrespective of its anatomical location. Further analysis of the age-specific incidence curves indicated that the male predominance of intestinal subtype was due to a 17.3-year delay of development of this cancer in women.9

The reason for the difference in the development of upper gastrointestinal cancer in women versus men is unclear and deserves further consideration and investigation. There are several possible mechanisms for a delay in development of the adenocarcinoma in females or facilitated development of those tumours in males. Protective effects of reproduction system components in females including oestrogen, progesterones and other hormones were main target of several investigations, but the results still remain inconsistent.10, 11, 12 Different body iron storage in men and women is another suspected risk factor. Biologically active iron components have been shown to be involved in many inflammatory and carcinogenic pathways.13, 14, 15 The role of mucosal iron radicals in Barrett’s metaplasia and oesophageal adenocarcinoma is one of the new challenging fields of research and need to be elucidated.

Non-endogenous risk factors of oesophageal and gastric adenocarcinomas may also contribute to differences in cancer incidence by sex. Helicobacter pylori infection as the essential factor in the carcinogenic pathway of most gastric adenocarcinomas has a reasonably equal prevalence in men and women.16, 17, 18 In the same manner, gastro-oesophageal reflux disease, as the main risk factor of oesophageal adenocarcinoma, is unlikely to show dramatic differences in prevalence between men and women,19 although, there are no reliable data in this regard because of variable definitions of the disease. Dietary and other life style risk factors of gastric and oesophageal adenocarcinoma might be among suspected factors for these sex differences; however, no current candidates can explain the difference in incidence.

Tobacco smoking is a well-established risk factor for upper gastrointestinal cancers. Smoking is a modest but consistent risk factor for non-cardia gastric cancer in populations with different demographic and ethnic backgrounds.20, 21, 22, 23 An association between smoking and oesophageal adenocarcinoma has been shown by several studies.21, 24, 25 The male predominance of some common cancers has been linked to different rates of smoking among males and females, as more men than women smoke in many different geographic parts of the world. For example, incidence rates of lung cancer have historically been higher in men than in women worldwide. Yet as the prevalence of smoking in men and women has become more similar, incidence rates of lung cancer in both sexes have also converged.26, 27 Data from large cohort studies indicate similar incidence rates of lung cancer in men and women with similar smoking histories.28, 29 Although the role of smoking in the development of upper gastrointestinal adenocarcinomas is not as large as those of lung, the potential role of tobacco smoking as an explanation for the predominance of these tumours in men has not been evaluated. The aim of the current study is to investigate the role of tobacco smoking in the male predominance of upper gastrointestinal adenocarcinomas in a well-defined population of the prospective United States NIH-AARP Diet and Health Study.

Section snippets

Materials and methods

The NIH-AARP Diet and Health Study was initiated in 1995–1996 when a baseline questionnaire was mailed to 3.5 million AARP members aged 50–71 years who resided in eight states (California, Florida, Georgia, Louisiana, Michigan New Jersey, North Carolina and Pennsylvania).30 Questionnaires were completed by 617,119 individuals, 566,402 of these questionnaires were completed in satisfactory detail. We excluded respondents with prevalent cancer (except non-melanoma skin cancer, 51,205), subjects

Results

After 2,013,142-person years follow-up, there were 821 new upper gastrointestinal adenocarcinomas, comprising 338 of the oesophagus, 261 of the gastric cardia and 222 of the gastric non-cardia in men. In women, after 1,351,958-person years follow-up, there were 147 new adenocarcinomas, which included 23 of the oesophagus, 36 of the gastric cardia and 88 of the gastric non-cardia. The age-standardised incidence rate (cases/100,000-person years) of all adenocarcinoma sites were 40.5 (95% CI:

Discussion

We investigated whether the male predominance of upper GI adenocarcinoma could be explained by differences in tobacco smoking histories by sex. We found that the male predominance was similar in smokers and non-smokers overall and for oesophageal, gastric cardia and gastric non-cardia sub-sites. Our results suggest that the male predominance of upper GI adenocarcinomas cannot be explained by differences in smoking histories or by differing risks for the association between smoking and risk of

Conflict of interest statement

None declared.

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