Risk factors for prostate cancer incidence and progression in the health professionals follow-up study

Abstract

Risk factors for prostate cancer could differ for various sub-groups, such as for "aggressive" and "non-aggressive" cancers or by grade or stage. Determinants of mortality could differ from those for incidence. Using data from the Health Professionals Follow-Up Study, we re-examined 10 factors (cigarette smoking history, physical activity, BMI, family history of prostate cancer, race, height, total energy consumption, and intakes of calcium, tomato sauce and alpha-linolenic acid) using multivariable Cox regression in relation to multiple subcategories for prostate cancer risk. These were factors that we previously found to be predictors of prostate cancer incidence or advanced prostate cancer in this cohort, and that have some support in the literature. In this analysis, only 4 factors had a clear statistically significant association with overall incident prostate cancer: African-American race, positive family history, higher tomato sauce intake (inversely) and alpha-linolenic acid intake. In contrast, for fatal prostate cancer, recent smoking history, taller height, higher BMI, family history, and high intakes of total energy, calcium and alpha-linolenic acid were associated with a statistically significant increased risk. Higher vigorous physical activity level was associated with lower risk. In relation to these risk factors, advanced stage at diagnosis was a good surrogate for fatal prostate cancer, but high-grade (Gleason >/= 7 or Gleason >/= 8) was not. Only for high calcium intake was there a close correspondence for associations among high-grade cancer, advanced and fatal prostate cancer. Tomato sauce (inversely) and alpha-linolenic acid (positively) intakes were strong predictors of advanced cancer among those with low-grade cancers at diagnosis. Although the proportion of advanced stage cancers was much lower after PSA screening began, risk factors for advanced stage prostate cancers were similar in the pre-PSA and PSA era. The complexity of the clinical and pathologic manifestations of prostate cancer must be considered in the design and interpretation of studies.

Figure 1

Multivariable relative risks and 95% confidence intervals (in ()’s) for the high category versus low or reference category for selected variables from Cox models separately for total prostate cancer incidence and fatal prostate cancer in the Health Professionals Follow-Up Study. The models included age, time period, BMI at age 21 years, height, cigarette pack-years in the previous 10 years, vigorous physical activity level, family history of prostate cancer, history of diabetes mellitus, race, and intakes of total calories, processed meat, fish, α-linolenic acid, tomato sauce, and vitamin E supplements. For BMI, reference group is <23 kg/m² for fatal prostate cancer. P denotes p-value for trend.

Figure 2

Multivariable relative risk, and 95% confidence intervals (in ()’s) for the high category versus low or reference category for selected variables from Cox models separately for high-grade prostate cancer (Gleason ≥ 7) and low-grade prostate cancer (Gleason ≤ 6) in the Health Professionals Follow-Up Study. The models included age, time period, BMI at age 21 years, height, cigarette pack-years in the previous 10 years, vigorous physical activity level, family history of prostate cancer, history of diabetes mellitus, race, and intakes of total calories, processed meat, fish, α-linolenic acid, tomato sauce, and vitamin E supplements. P denotes p-value for trend.