The association of menstrual and reproductive factors with upper gastrointestinal tract cancers in the NIH-AARP cohort.
BACKGROUND
In most populations, incidence rates of upper gastrointestinal (UGI) tract cancers (head and neck, esophagus, and stomach) are higher among men than among women. Established risk factors do not appear to explain these differences, suggesting a possible role for sex hormones.


METHODS
201,506 women of the NIH-AARP Diet and Health cohort completed a questionnaire in 1995-1996. Hazard ratios and 95% confidence intervals were estimated from Cox proportional hazards models.


RESULTS
During follow-up through 2003, 162 incident adenocarcinomas (ACs; esophagus, N = 25, and stomach, N = 137) and 353 incident squamous cell carcinomas (SCCs; head and neck, n = 297, and esophagus, N = 56) occurred. Among examined exposures, older age at menopause was associated inversely with SCC (P(trend) across categories = .013) but not AC (P(trend) = .501). Use of menopausal hormone therapy (MHT) was significantly associated with lower risk of SCC (hazard ratio [HR] = 0.77, 0.62-0.96) and nonsignificantly associated with lower risk of AC (HR = 0.81, 0.59-1.12). A subset (N = 127,386) of the cohort completed a more detailed MHT questionnaire a year after baseline. In 74,372 women with intact uteri, ever use of estrogen-progestin MHT conferred 0.47 (0.30-0.75) times the risk for SCC and 0.52 (0.26-1.07) times the risk for ACC. In 51,515 women with a hysterectomy before baseline, we found no associations between use of estrogen MHT and AC or SCC.


CONCLUSIONS
Higher estrogen and progesterone levels may be related inversely to UGI cancers and in this way help explain lower incidence rates in women compared with men.
Freedman
Neal D
ND
Division of Cancer Epidemiology and Genetics, Nutritional Epidemiology Branch, 6120 Executive Blvd, EPS/320, MSC 7232, Rockville, MD 20852, USA. freedmanne@mail.nih.gov
Lacey
James V
JV
Hollenbeck
Albert R
AR
Leitzmann
Michael F
MF
Schatzkin
Arthur
A
Abnet
Christian C
CC
D000230:Adenocarcinoma / Q000453:epidemiology*; D000368:Aged; D000428:Alcohol Drinking; D002294:Carcinoma, Squamous Cell / Q000453:epidemiology; D015914:Estrogen Replacement Therapy / Q000009:adverse effects; D005260:Female; D005770:Gastrointestinal Neoplasms / Q000453:epidemiology*; D006258:Head and Neck Neoplasms / Q000453:epidemiology*; D006306:Health Surveys; D006801:Humans; D008297:Male; D008598:Menstruation; D008875:Middle Aged; D011446:Prospective Studies; D017584:Reproductive History; D012306:Risk; D012727:Sex Characteristics; D012907:Smoking; D014481:United States / Q000453:epidemiology