Yonsei Med J.  2018 Jan;59(1):28-34. 10.3349/ymj.2018.59.1.28.

Protective Effects of Female Reproductive Factors on Lauren Intestinal-Type Gastric Adenocarcinoma

• Kim SM
• Min BH
• Lee J
• An JY
• Lee JH
• Sohn TS
• Bae JM
• Kim JJ
• Kang WK
• Kim S
• Choi MG

• KMID: 2418845
• DOI: http://doi.org/10.3349/ymj.2018.59.1.28

Abstract

PURPOSE
Gastric cancer shows a male predominance that might be explained by protective effects from estrogens in females. Two Lauren classification histological subtypes, intestinal and diffuse, have distinct carcinogeneses. The purpose of this study was to estimate the effects of sex hormone on female gastric cancer according to Lauren classification.
MATERIALS AND METHODS
We reviewed medical records for and administered questionnaires, surveying reproductive and hormonal factors, to 758 patients who underwent gastrectomy for gastric cancer at Samsung Medical Center from May 2012 to November 2014. Clinicopathological characteristics were compared between females and males. The incidence of intestinal-type gastric cancer was compared between females subgroups, consist of premenopausal women and three groups of postmenopausal women (five-year intervals after menopause), and males. The association between reproductive factors and intestinal-type gastric cancer was analyzed by multivariate models for the female group.
RESULTS
In total, 227 females (29.9%) and 531 males (70.9%) were included in the analysis. Undifferentiated adenocarcinoma and diffuse-type histology were more frequent in female patients than male patients. While 221 (41.6%) male patients had intestinal-type gastric cancer, no premenopausal female patient had this type of gastric cancer. The incidence of intestinal-type gastric cancer increased with time after menopause, and was similar to males after 10 years from menopause. Parity was associated with an increased risk of intestinal-type gastric cancer in menopausal women.
CONCLUSION
These findings support that female sex hormones might be protective against intestinal-type gastric cancer.

Keyword

Female; sex hormone; gastric cancer

MeSH Terms

Adenocarcinoma/*pathology
Female
Humans
Male
Middle Aged
Multivariate Analysis
Postmenopause
Protective Agents/*metabolism
*Reproduction
Risk Factors
Stomach Neoplasms/*pathology/surgery
Protective Agents

Figure

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  Fig. 1 Flow diagram of patient recruitment.

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  Fig. 2 Number of intestinal and diffuse subtype gastric cancers in male and female subgroups classified according to cumulative 5-year intervals after menopause. *p-value was calculated compared to male groups.

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  Fig. 3 Proportion of intestinal and diffuse subtype gastric cancers in male and female subgroups classified according to cumulative 5-year intervals after menopause.

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  Fig. 4 Number of intestinal and diffuse subtype gastric cancers in male and female subgroups classified according to 5-year intervals after menopause.

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  Fig. 5 Proportion of intestinal and diffuse subtype gastric cancers in male and female subgroups classified according to 5-year intervals after menopause.

Reference

1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015; 136:E359–E386.

2. Forman D BF, Brewster DH, Gombe Mbalawa C, Kohler B, Piñeros M, Steliarova-Foucher E, et al. Cancer incidence in five continents, CI5plus. IARC CancerBase No. 9. Lyon: International Agency for Research on Cancer;2014.

3. Freedman ND, Chow WH, Gao YT, Shu XO, Ji BT, Yang G, et al. Menstrual and reproductive factors and gastric cancer risk in a large prospective study of women. Gut. 2007; 56:1671–1677.

4. Chandanos E, Lindblad M, Jia C, Rubio CA, Ye W, Lagergren J. Tamoxifen exposure and risk of oesophageal and gastric adenocarcinoma: a population-based cohort study of breast cancer patients in Sweden. Br J Cancer. 2006; 95:118–122.

5. Helguero LA, Lindberg K, Gardmo C, Schwend T, Gustafsson JA, Haldosén LA. Different roles of estrogen receptors alpha and beta in the regulation of E-cadherin protein levels in a mouse mammary epithelial cell line. Cancer Res. 2008; 68:8695–8704.

6. Lauren P. The two histological main types of gastric carcinoma: diffuse and so-called intestinal-type carcinoma. An attempt at a histo-clinical classification. Acta Pathol Microbiol Scand. 1965; 64:31–49.

7. Ribeiro MM, Sarmento JA, Sobrinho Simöes MA, Bastos J. Prognostic significance of Lauren and Ming classifications and other pathologic parameters in gastric carcinoma. Cancer. 1981; 47:780–784.

8. Gurzu S, Kadar Z, Sugimura H, Bara T, Bara T Jr, Halmaciu I, et al. Gastric cancer in young vs old Romanian patients: immunoprofile with emphasis on maspin and mena protein reactivity. APMIS. 2015; 123:223–233.

9. Edge SB, Byrd DR, Compton CC, Fritz AG, Greene FL, Trotti A. AJCC cancer staging manual. 7th ed. New York: Springer;2010.

10. Yang H, Sukocheva OA, Hussey DJ, Watson DI. Estrogen, male dominance and esophageal adenocarcinoma: is there a link? World J Gastroenterol. 2012; 18:393–400.

11. Beral V. Million Women Study Collaborators. Breast cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2003; 362:419–427.

12. Beral V, Bull D, Reeves G. Million Women Study Collaborators. Endometrial cancer and hormone-replacement therapy in the Million Women Study. Lancet. 2005; 365:1543–1551.

13. Lacey JV Jr, Mink PJ, Lubin JH, Sherman ME, Troisi R, Hartge P, et al. Menopausal hormone replacement therapy and risk of ovarian cancer. JAMA. 2002; 288:334–341.

14. Poulter NR, Meirik O, Chang CL, Farley TMM, Kelaghan J, Marmot MG, et al. Acute myocardial infarction and combined oral contraceptives: results of an international multicentre case-control study. WHO Collaborative Study of Cardiovascular Disease and Steroid Hormone Contraception. Lancet. 1997; 349:1202–1209.

15. Grady D, Gebretsadik T, Kerlikowske K, Ernster V, Petitti D. Hormone replacement therapy and endometrial cancer risk: a meta-analysis. Obstet Gynecol. 1995; 85:304–313.

16. Grodstein F, Newcomb PA, Stampfer MJ. Postmenopausal hormone therapy and the risk of colorectal cancer: a review and meta-analysis. Am J Med. 1999; 106:574–582.

17. Lindblad M, Ye W, Rubio C, Lagergren J. Estrogen and risk of gastric cancer: a protective effect in a nationwide cohort study of patients with prostate cancer in Sweden. Cancer Epidemiol Biomarkers Prev. 2004; 13:2203–2207.

18. Curtis RE, Boice JD Jr, Shriner DA, Hankey BF, Fraumeni JF Jr. Second cancers after adjuvant tamoxifen therapy for breast cancer. J Natl Cancer Inst. 1996; 88:832–834.

19. Furukawa H, Iwanaga T, Koyama H, Taniguchi H. Effect of sex hormones on the experimental induction of cancer in rat stomach-a preliminary study. Digestion. 1982; 23:151–155.

20. Sipponen P, Correa P. Delayed rise in incidence of gastric cancer in females results in unique sex ratio (M/F) pattern: etiologic hypothesis. Gastric Cancer. 2002; 5:213–219.

21. Qiu MZ, Wang ZQ, Zhang DS, Luo HY, Zhou ZW, Wang FH, et al. Clinicopathological characteristics and prognostic analysis of gastric cancer in the young adult in China. Tumour Biol. 2011; 32:509–514.

22. Chandanos E, Rubio CA, Lindblad M, Jia C, Tsolakis AV, Warner M, et al. Endogenous estrogen exposure in relation to distribution of histological type and estrogen receptors in gastric adenocarcinoma. Gastric Cancer. 2008; 11:168–174.

23. Ibrahim A, Morais S, Ferro A, Lunet N, Peleteiro B. Sex-differences in the prevalence of Helicobacter pylori infection in pediatric and adult populations: systematic review and meta-analysis of 244 studies. Dig Liver Dis. 2017; 49:742–749.

24. Yi JH, Do IG, Jang J, Kim ST, Kim KM, Park SH, et al. Anti-tumor efficacy of fulvestrant in estrogen receptor positive gastric cancer. Sci Rep. 2014; 4:7592.